Parkinson's disease(PD)is a progressive neurodegenerative disorder with clinical symptoms of involuntary or uncontrollable movements such as tremors,rigidity,and incoordination.The learning deficit is largely over...Parkinson's disease(PD)is a progressive neurodegenerative disorder with clinical symptoms of involuntary or uncontrollable movements such as tremors,rigidity,and incoordination.The learning deficit is largely overlooked in the past because it is generally less impaired in the early stages of PD than in Alzheimer's disease.展开更多
Parkinson’s disease can affect not only motor functions but also cognitive abilities,leading to cognitive impairment.One common issue in Parkinson’s disease with cognitive dysfunction is the difficulty in executive ...Parkinson’s disease can affect not only motor functions but also cognitive abilities,leading to cognitive impairment.One common issue in Parkinson’s disease with cognitive dysfunction is the difficulty in executive functioning.Executive functions help us plan,organize,and control our actions based on our goals.The brain area responsible for executive functions is called the prefrontal co rtex.It acts as the command center for the brain,especially when it comes to regulating executive functions.The role of the prefrontal cortex in cognitive processes is influenced by a chemical messenger called dopamine.However,little is known about how dopamine affects the cognitive functions of patients with Parkinson’s disease.In this article,the authors review the latest research on this topic.They start by looking at how the dopaminergic syste m,is alte red in Parkinson’s disease with executive dysfunction.Then,they explore how these changes in dopamine impact the synaptic structure,electrical activity,and connection components of the prefrontal cortex.The authors also summarize the relationship between Parkinson’s disease and dopamine-related cognitive issues.This information may offer valuable insights and directions for further research and improvement in the clinical treatment of cognitive impairment in Parkinson’s disease.展开更多
Despite decades of dedicated resea rch,Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disorder for which the mechanisms of onset are sti unc ear.AD is cha racterized by featured histo...Despite decades of dedicated resea rch,Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disorder for which the mechanisms of onset are sti unc ear.AD is cha racterized by featured histological alterations including amyloid-beta (AB) plaque deposition,accumulation of neurofibrillary to ngles of hyperphosphorylated-tau,and neuronal loss,accompanied by progressive cognitive decline and behavioral changes.展开更多
Melatonin and dopamine can potentially prevent waterlogging stress in apples.The current study investigated the mechanism by which melatonin and dopamine alleviate apple waterlogging stress.This study demonstrated tha...Melatonin and dopamine can potentially prevent waterlogging stress in apples.The current study investigated the mechanism by which melatonin and dopamine alleviate apple waterlogging stress.This study demonstrated that melatonin and dopamine alleviated waterlogging by removing reactive oxygen species(ROS),and that the nitric oxide(NO)content and nitrate reductase(NR)activity were significantly correlated.Melatonin and dopamine were also found to recruit different candidate beneficial endophytes(melatonin:Novosphingobium,Propionivibrio,and Cellvibrio;dopamine:Hydrogenophaga,Simplicispira,Methyloversatilis,Candidatus_Kaiserbacteria,and Humicola),and these endophytes were significantly and positively correlated with plant growth.Network analyses showed that melatonin and dopamine significantly affected the endophytic bacterial and fungal communities under waterlogging stress.The metabolomic results showed that melatonin and dopamine led to waterlogging resistance by upregulating the abundance of beneficial substances such as amino acids,flavonoids,coumarins,and organic acids.In addition,melatonin and dopamine regulated the physicochemical properties of the soil,which altered the endophyte community and affected plant growth.The co-occurrence network demonstrated close and complex relationships among endophytes,metabolites,soil,and the plants.Our results demonstrate that melatonin and dopamine alleviate waterlogging stress in apples by recruiting beneficial endophytes to enhance physiological resilience.This study provides new insights into how melatonin and dopamine alleviate stress and a theoretical basis for synergistic beneficial microbial resistance to waterlogging stress.展开更多
Alzheimer's disease is a common neurodegenerative disorder in older adults.Despite its prevalence,its pathogenesis remains unclea r.In addition to the most widely accepted causes,which in clude excessive amyloid-b...Alzheimer's disease is a common neurodegenerative disorder in older adults.Despite its prevalence,its pathogenesis remains unclea r.In addition to the most widely accepted causes,which in clude excessive amyloid-beta aggregation,tau hyperphosphorylation,and deficiency of the neurotransmitter acetylcholine,numerous studies have shown that the dopaminergic system is also closely associated with the occurrence and development of this condition.Dopamine is a crucial catecholaminergic neurotransmitter in the human body.Dopamine-associated treatments,such as drugs that target dopamine receptor D and dopamine analogs,can improve cognitive function and alleviate psychiatric symptoms as well as ameliorate other clinical manifestations.Howeve r,therapeutics targeting the dopaminergic system are associated with various adverse reactions,such as addiction and exacerbation of cognitive impairment.This review summarizes the role of the dopaminergic system in the pathology of Alzheimer's disease,focusing on currently available dopamine-based therapies for this disorder and the common side effects associated with dopamine-related drugs.The aim of this review is to provide insights into the potential connections between the dopaminergic system and Alzheimer's disease,thus helping to clarify the mechanisms underlying the condition and exploring more effective therapeutic options.展开更多
A novel strategy was developed to prepare the methacrylic gelatin-dopamine(GelMA-DA)/Ag nanoparticles(NPs)/graphene oxide(GO) composite hydrogels with good biocompatibility,mechanical properties,and antibacterial acti...A novel strategy was developed to prepare the methacrylic gelatin-dopamine(GelMA-DA)/Ag nanoparticles(NPs)/graphene oxide(GO) composite hydrogels with good biocompatibility,mechanical properties,and antibacterial activity.Mussel-inspired DA was utilized to modify the GelMA molecules,which imparts good adhesive performance to the hydrogels.GO,interfacial enhancer,not only improves mechanical properties of the hydrogels,but also provides anchor sites for loading Ag NPs through numerous oxygencontaining functional groups on the surface.The experimental results show that the GelMA/Ag NPs/GO hydrogels have good biocompatibility,and exhibit a swelling rate of 202±16%,the lap shear strength of 147±17 kPa,and compressive modulus of 136±53 kPa,in the case of the Ag NPs/GO content of 2 mg/mL.Antibacterial activity of the hydrogels against both gram-negative and gram-positive bacteria is dependent on the Ag NPs/GO content derived from the release of Ag^(+).Furthermore,the GelMA/Ag NPs/GO hydrogels possess good adhesive ability,which is resistant to highly twisted state when stuck on the surface of pigskin.These results demonstrate promising potential of the GelMA-DA/Ag NPs/GO hydrogels as wound dressings for biomedical applications in clinical and emergent treatment.展开更多
Dopamine can be used to treat depression,myocardial infarction,and other diseases.However,few reports are available on the de novo microbial synthesis of dopamine from low-cost substrate.In this study,integrated omics...Dopamine can be used to treat depression,myocardial infarction,and other diseases.However,few reports are available on the de novo microbial synthesis of dopamine from low-cost substrate.In this study,integrated omics technology was used to explore the dopamine metabolism of a novel marine multi-stress-tolerant aromatic yeast Meyerozyma guilliermondii GXDK6.GXDK6 was found to have the ability to biosynthesize dopamine when using glucose as the substrate.14 key genes for the biosynthesis of dopamine were identified by whole genome-wide analysis.Transcriptomic and proteomic data showed that the expression levels of gene AAT2 encoding aspartate aminotransferase(regulating dopamine anabolism)were upregulated,while gene AO-I encoding copper amine oxidase(involved in dopamine catabolism)were downregulated under 10%NaCl stress compared with non-NaCl stress,thereby contributing to biosynthesis of dopamine.Further,the amount of dopamine under 10%NaCl stress was 2.51-fold higher than that of zero NaCl,which was consistent with the multi-omics results.Real-time fluorescence quantitative PCR(RT-qPCR)and high-performance liquid chromatography(HPLC)results confirmed the metabolic model of dopamine.Furthermore,by overexpressing AAT2,AST enzyme activity was increased by 24.89%,the expression of genes related to dopamine metabolism was enhanced,and dopamine production was increased by 56.36%in recombinant GXDK6AAT2.In conclusion,Meyerozyma guilliermondii GXDK6 could utilize low-cost carbon source to synthesize dopamine,and NaCl stress promoted the biosynthesis of dopamine.展开更多
Apple replant disease(ARD)is a complex agricultural problem caused by multiple stressors that can lead to increased reactive oxygen species(ROS)levels and limited nutrient utilization in plants.However,existing counte...Apple replant disease(ARD)is a complex agricultural problem caused by multiple stressors that can lead to increased reactive oxygen species(ROS)levels and limited nutrient utilization in plants.However,existing countermeasures cannot effectively address this challenge.Here,we used Malus hupehensis as a test organism to investigate whether the pleiotropic molecule dopamine can alleviate ARD using pot experiments.Exogenous application of 100μmol L-1 dopamine significantly promoted the growth of apple seedlings in the replanted soil,with a relative growth rate increase of 17.44%.Our results revealed two major pathways by which dopamine regulates ARD resistance in apple trees.First,dopamine effectively reduces the level of ROS and activates the expression of genes related to nitrogen(N)transport and metabolism.Among those genes,MdNLP5,MdNRT1.1,MdNLP2,MdNRT2.5,MdNLP3,MdNRT2.4,MdNADH-GAGOT,and MdFd-GAGOT were strongly regulated by dopamine.These regulatory effects promoted the uptake and utilization of soil N by the plants.Second,dopamine improved the physical and chemical properties,enhanced microbial community diversity,and promoted mutual cooperation between microbial communities in the soil.Furthermore,dopamine altered the microbial structure of rhizosphere soil(upregulating Clostridiales,Gaiellales,Sordariales and Mortierellales;downregulating Micrococcales,Longimicrobiales,Hypocreales and Cystobasidiales).Notably,dopamine significantly upregulated the abundances of Gaiella and Mortierella,both of which were positively correlated with soil urease activity,soil available N content,plant growth and N uptake.Dopamine also significantly downregulated the abundance of the plant pathogen Gibberella(by 11.71-fold)in replant soil.Our results provide insights into the mechanisms by which dopamine promotes ARD resistance,and can promote the sustainable development of the apple industry.展开更多
Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia.Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia.Cu...Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia.Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia.Currently,studies have reported increased oscillation power in cases of levodopa-induced dyskinesia.However,little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced dyskinesia.Furthermore,the role of the dopamine D3 receptor,which is implicated in levodopa-induced dyskinesia,in movement disorder-related changes in neural oscillations is unclear.We found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson’s disease.Furthermore,levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components,as well as bidirectional primary motor cortex(M1)↔dorsolateral striatum gamma flow.Administration of PD128907(a selective dopamine D3 receptor agonist)induced dyskinesia and excessive gamma oscillations with a bidirectional M1↔dorsolateral striatum flow.However,administration of PG01037(a selective dopamine D3 receptor antagonist)attenuated dyskinesia,suppressed gamma oscillations and cortical gamma aperiodic components,and decreased gamma causality in the M1→dorsolateral striatum direction.These findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity,and that it has potential as a therapeutic target for levodopa-induced dyskinesia.展开更多
Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism....Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism.This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism.We conducted a thorough literature search using reputable databases such as PubMed and Web of Science.Selection criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical applications.The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis.Moreover,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker.This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion.In summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.展开更多
AIM:To evaluate effects of endogenous dopamine induced by low concentration atropine eye drops on choroidal neovascularization(CNV)in high myopia mice.METHODS:The C57BL/6J mice were deprived of the right eye for 4wk,a...AIM:To evaluate effects of endogenous dopamine induced by low concentration atropine eye drops on choroidal neovascularization(CNV)in high myopia mice.METHODS:The C57BL/6J mice were deprived of the right eye for 4wk,and the high myopia was diagnosed by optometry,the diopter was less than-6.00 D,and CNV was induced by 532 nm laser.The changes of dopamine D1 receptor(DRD1),dopamine D2 receptor(DRD2),and vascular endothelial growth factor A(VEGFA)were detected by Western blot technology at 0.5,1,2h,and 7d after 0.01%,0.05%,and 0.1%atropine eye drops,respectively,the area of CNV was measured.RESULTS:Significant increases were observed on the expression of DRD2 in mouse high myopia model at 0.5,1,2h,7d with 0.05%and 0.1%atropine eye drops(P<0.05).Significant decreases were observed on the expression of DRD1 and VEGFA in mouse high myopia model at 0.5,1,2h,7d with 0.05%and 0.1%atropine eye drops(P<0.05).The area of CNV induced by laser in the drug-treated group was significantly smaller than that in the control group,and the higher the concentration,the more significant the inhibitory effect(P<0.05).CONCLUSION:The 0.01%,0.05%,0.1%atropine eye drops can decrease the level of VEGFA and inhibit high myopia CNV indirectly by up-regulating the level of DRD2 and down-regulating the level of DRD1,and the effect of 0.05%and 0.1%atropine eye drops is more significant.展开更多
Studies have found that the absence of glial cell line-derived neurotrophic factor may be the primary risk factor for Parkinson’s disease. However, there have not been any studies conducted on the potential relations...Studies have found that the absence of glial cell line-derived neurotrophic factor may be the primary risk factor for Parkinson’s disease. However, there have not been any studies conducted on the potential relationship between glial cell line-derived neurotrophic factor and cognitive performance in Parkinson’s disease. We first performed a retrospective case-control study at the Affiliated Hospital of Xuzhou Medical University between September 2018 and January 2020 and found that a decreased serum level of glial cell line-derived neurotrophic factor was a risk factor for cognitive disorders in patients with Parkinson’s disease. We then established a mouse model of Parkinson’s disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and analyzed the potential relationships among glial cell line-derived neurotrophic factor in the prefrontal cortex, dopamine transmission, and cognitive function. Our results showed that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex weakened dopamine release and transmission by upregulating the presynaptic membrane expression of the dopamine transporter, which led to the loss and primitivization of dendritic spines of pyramidal neurons and cognitive impairment. In addition, magnetic resonance imaging data showed that the long-term lack of glial cell line-derived neurotrophic factor reduced the connectivity between the prefrontal cortex and other brain regions, and exogenous glial cell line-derived neurotrophic factor significantly improved this connectivity. These findings suggested that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex leads to neuroplastic degeneration at the level of synaptic connections and circuits, which results in cognitive impairment in patients with Parkinson’s disease.展开更多
The^(10)boron neutron-capture therapy(BNCT)is an emerging antitumoral method that shows increasing biomedical interest.BNCT is based on the selective accumulation of the^(10)boron isotope within the tumor,which is the...The^(10)boron neutron-capture therapy(BNCT)is an emerging antitumoral method that shows increasing biomedical interest.BNCT is based on the selective accumulation of the^(10)boron isotope within the tumor,which is then irradiated with low-energy thermal neutrons,generating nuclear fission that produces 7lithium,4helium,andγrays.Simple catechol-borate esters have been rather overlooked as precursors of melanin biosynthesis,and therefore,a proof-of-concept approach for using dopamine-borate(DABO)as a suitable boron-containing candidate for potential BNCT is presented here.DABO can spontaneously oxidize and autopolymerize in vitro,giving a soluble,eumelaninlike brown-black poly-DABO product.Melanotic melanoma cell cultures treated with 1 mM DABO for 24 and 48 h were viable and showed no signs of damage or cell death.The stability and possible trans-esterification of DABO is shortly discussed.Chemical calculations and quantitative structure-activity relationships(QSAR)analysis of DABO and the BNCT agent BPA indicated that they should be cell permeant and accumulate within lysosomes and melanosomes.Molecular modeling allows visualization of both the DABO precursor and the structure of a borate derivative of the proposed catechol-porphycene model for eumelanin,showing interesting features from molecular orbital calculations.The main difference between DABO and other agents,such as BPA,is that it is not a boronic acid nor a boron cluster.This simple catechol-borate ester(protected from oxidation and blackening)could be administrated to living cells and organisms,in which biosynthesis of boron-melanin in melanoma melanocytes can lead to improved BNCT.展开更多
Dopamine has demonstrated promise as a stress-relief substance.However,the function of dopamine in Cd tolerance and its mechanism remains largely unknown.The current study was performed to investigate the mechanism of...Dopamine has demonstrated promise as a stress-relief substance.However,the function of dopamine in Cd tolerance and its mechanism remains largely unknown.The current study was performed to investigate the mechanism of dopamine on alleviating apple Cd stress through regular application of CdCl2 and dopamine solution to potting soil.The results indicated that dopamine significantly reduced reactive oxygen species(ROS)and Cd accumulation and alleviated the inhibitory effect of Cd stress on the growth of apple plants through activation of the antioxidant system,enhancement of photosynthetic capacity,and regulation of gene expression related to Cd absorption and detoxification.The richness of the rhizosphere microbial community increased,and community composition and assembly were affected by dopamine treatment.Network analysis of microbial communities showed that the numbers of nodes and total links increased significantly after dopamine treatment,while the keystone species shifted.Linear discriminant analysis effect size indicated that some biomarkers were significantly enriched after dopamine treatment,suggesting that dopamine induced plants to recruit potentially beneficial microorganisms(Pseudoxanthomonas,Aeromicrobium,Bradyrhizobium,Frankia,Saccharimonadales,Novosphingobium,and Streptomyces)to resist Cd stress.The co-occurrence network showed several metabolites that were positively correlated with relative growth rate and negatively correlated with Cd accumulation,suggesting that potentially beneficial microorganisms may be attracted by several metabolites(L-threonic acid,profenamine,juniperic acid and(3β,5ξ,9ξ)-3,6,19-trihydroxyurs-12-en-28-oic acid).Our results demonstrate that dopamine alleviates Cd stress in apple trees by recruiting beneficial microorganisms to enhance the physiological resilience revealed.This study provides an effective means to reduce the harm to agricultural production caused by heavy metals.展开更多
BACKGROUND Dopamine and cyclic adenosine monophosphate(cAMP)-regulated phosphop-rotein with an apparent Mr of 32000(DARPP-32)is a protein that is involved in regulating dopamine and cAMP signaling pathways in the brai...BACKGROUND Dopamine and cyclic adenosine monophosphate(cAMP)-regulated phosphop-rotein with an apparent Mr of 32000(DARPP-32)is a protein that is involved in regulating dopamine and cAMP signaling pathways in the brain.However,recent studies have shown that DARPP-32 is also expressed in other tissues,including colorectal cancer(CRC),where its function is not well understood.AIM To explore the effect of DARPP-32 on CRC progression.METHODS The expression levels of DARPP-32 were assessed in CRC tissues using both quantitative polymerase chain reaction and immunohistochemistry assays.The proliferative capacity of CRC cell lines was evaluated with Cell Counting Kit-8 and 5-ethynyl-2’-deoxyuridine assays,while apoptosis was measured by flow cytometry.The migratory and invasive potential of CRC cell lines were deter-mined using wound healing and transwell chamber assays.In vivo studies involved monitoring the growth rate of xenograft tumors.Finally,the underlying molecular mechanism of DARPP-32 was investigated through RNA-sequencing and western blot analyses.RESULTS DARPP-32 was frequently upregulated in CRC and associated with abnormal clinicopathological features in CRC.Overexpression of DARPP-32 was shown to promote cancer cell proliferation,migration,and invasion and reduce apoptosis.DARPP-32 knockdown resulted in the opposite functional effects.Mechanistically,DARPP-32 may regulate the phosphoinositide 3-kinase(PI3K)/AKT signaling pathway in order to carry out its biological function.CONCLUSION DARPP-32 promotes CRC progression via the PI3K/AKT signaling pathway.展开更多
Pediatric autoimmune neuropsychiatric disorders associated with group A streptococcal infections (PANDAS) is a concept that is used to characterize a subset of children with neuropsychiatric symptoms, tic disorders, o...Pediatric autoimmune neuropsychiatric disorders associated with group A streptococcal infections (PANDAS) is a concept that is used to characterize a subset of children with neuropsychiatric symptoms, tic disorders, or obsessive-compulsive disorder (OCD), whose symptoms are exacerbated by group A streptococcal (GAS) infection. PANDAS has been known to cause a sudden onset of reward deficiency syndrome (RDS). RDS includes multiple disorders that are characterized by dopaminergic signaling dysfunction in the brain reward cascade (BRC), which may result in addiction, depression, avoidant behaviors, anxiety, tic disorders, and/or OCD. According to research by Blum et al., the dopamine receptor D2 (DRD2) gene polymorphisms are important prevalent genetic determinants of RDS. The literature demonstrates that infections like Borrelia and Lyme, as well as other infections like group A beta-hemolytic streptococcal (GABHS), can cause an autoimmune reaction and associated antibodies target dopaminergic loci in the mesolimbic region of the brain, which interferes with brain function and potentially causes RDS-like symptoms/behaviors. The treatment of PANDAS remains controversial, especially since there have been limited efficacy studies to date. We propose an innovative potential treatment for PANDAS based on previous clinical trials using a pro-dopamine regulator known as KB220 variants. Our ongoing research suggests that achieving “dopamine homeostasis” by precision-guided DNA testing and pro-dopamine modulation could result in improved therapeutic outcomes.展开更多
Dopamine (DA) is one of the brain's fundamental neurotransmitters. Despite the fact that the dopaminergic synapses constitute less than 1% of all brain synapses, DA is implicated in a number of critical physiologic...Dopamine (DA) is one of the brain's fundamental neurotransmitters. Despite the fact that the dopaminergic synapses constitute less than 1% of all brain synapses, DA is implicated in a number of critical physiological functions and in the pathogenesis of important psychiatric diseases such as schizophrenia, attention-deficit/hyperactivity disorder (ADHD), Parkinson's disease (PD) and others.展开更多
Objective To investigate the influence of dopamine (DA) and DA receptor's antagonist on the transmission of noxious information in the central nervous system of normal rats or morphinistic rats. Methods The influen...Objective To investigate the influence of dopamine (DA) and DA receptor's antagonist on the transmission of noxious information in the central nervous system of normal rats or morphinistic rats. Methods The influence of DA on the electric activity of the pain-excited neuron (PEN) in the caudate nucleus (Cd) of normal rats or morphinistic rats was recorded after the sciatic nerve was noxiously stimulated. Results DA shortened the average latency of the evoked discharge of PEN in the Cd of normal rats, indicating that DA could increase the activity of PEN and pain sensitivity in normal rats. This effect could be inhibited by Droperidol. DA increased the average latency of the evoked discharge of PEN in the Cd of morphinistic rats, indicating that DA could inhibit the activity of PEN and pain sensitivity in morphinistic rats. Conclusion The responses to painful stimulation were completely opposite between normal rats and morphinistic rats after the intracerebroventricular injection of DA.展开更多
Aim To investigate the effect of liriodendrin, an extract from Fraxinus sielboldiana blume belonging to the Oleaceae family, on dopamine-induced cytotoxicity in human neuroblastoma SH-SY5Y cells. Methods Cell viabilit...Aim To investigate the effect of liriodendrin, an extract from Fraxinus sielboldiana blume belonging to the Oleaceae family, on dopamine-induced cytotoxicity in human neuroblastoma SH-SY5Y cells. Methods Cell viability was processed when treated with 50 μmol·L^-1 of dopamine for 24 h by MTT assay. Early apoptosis, late apoptosis/necrosis were analyzed by flow cytometry using Annexin V-FITC and propidium iodide (PI) double-staining, respectively. Generation of reactive oxygen species (ROS) was assessed by DCFH-DA, an oxidation-sensitive fluorescent probe. To evaluate mitochondrion membrane potential (Δψm) using flow cytometry with the fluorescent dye Rhodamine 123. The transcriptional level of P53 was studied using RT- PCR. Results The dopamine-induced loss of cell viability was significantly attenuated by liriodendrin treatment at the concentration of 10^-8, 10^-7, 10^-6, 10^-5 and 10^-4 mol·L^-1. The protective effects of liriodendrin (10^-7, 10^-6 and 10^-5 mol·L^-1) on dopamine-induced cytotoxicity may be ascribed to its anti-oxidative properties by reducing ROS level and anti-apoptotic effect via protection of Δψm. In addition, the effect of liriodendrin may involve the P53 pathway in apoptosis. Conclusion Liriodendrin may provide a useful therapeutic strategy for the treatment of neurodegenerative diseases such as Parkinson's disease (PD)展开更多
To understand the regulatory mechanisms of gonadotropin secretion in Rana rugulosa ,this study investigated the effects of dopamine (DA),estradiol (E 2) and testosterone (T) on the in vitro release of luteiniz...To understand the regulatory mechanisms of gonadotropin secretion in Rana rugulosa ,this study investigated the effects of dopamine (DA),estradiol (E 2) and testosterone (T) on the in vitro release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the pituitary fragments of female Rana rugulosa using a static incubation system and radio immunoassay (RIA). The results indicated that DA at the concentration from 0 1?μmol/L to 10?μmol/L inhibited the release of LH and FSH from the pituitary fragments of sexually pre mature or hibernating individuals,and the inhibitory effects enhanced with increasing concentrations of DA. E 2 at 1?μmol/L and 10?μmol/L significantly stimulated the release of LH of sexually pre mature individuals,but inhibited their FSH release at 0 1?μmol/L to 10?μmol/L;T had no obvious effects on their FSH release,but significantly inhibited their LH release at 10?μmol/L. Neither E 2 nor T,at the concentration from 0 1?μmol/L to 100?μmol/L,had obvious effects on the release of LH and FSH of hibernating individuals. The data suggest that DA and sexual steroids may have direct regulatory actions on LH and FSH release at the pituitary level in Rana rugulosa ,and the action of sexual steroids may relate to the gonadal development stages (seasons).展开更多
基金supported by the STI 2030-Major Projects,No.2021ZD0200500the Natural Science Foundation of Shanghai,No.21ZR1419700(both to SL)。
文摘Parkinson's disease(PD)is a progressive neurodegenerative disorder with clinical symptoms of involuntary or uncontrollable movements such as tremors,rigidity,and incoordination.The learning deficit is largely overlooked in the past because it is generally less impaired in the early stages of PD than in Alzheimer's disease.
基金supported by the National Natural Science Foundation of China,No.82101263Jiangsu Province Science Foundation for Youths,No.BK20210903Research Foundation for Talented Scholars of Xuzhou Medical University,No.RC20552114(all to CT)。
文摘Parkinson’s disease can affect not only motor functions but also cognitive abilities,leading to cognitive impairment.One common issue in Parkinson’s disease with cognitive dysfunction is the difficulty in executive functioning.Executive functions help us plan,organize,and control our actions based on our goals.The brain area responsible for executive functions is called the prefrontal co rtex.It acts as the command center for the brain,especially when it comes to regulating executive functions.The role of the prefrontal cortex in cognitive processes is influenced by a chemical messenger called dopamine.However,little is known about how dopamine affects the cognitive functions of patients with Parkinson’s disease.In this article,the authors review the latest research on this topic.They start by looking at how the dopaminergic syste m,is alte red in Parkinson’s disease with executive dysfunction.Then,they explore how these changes in dopamine impact the synaptic structure,electrical activity,and connection components of the prefrontal cortex.The authors also summarize the relationship between Parkinson’s disease and dopamine-related cognitive issues.This information may offer valuable insights and directions for further research and improvement in the clinical treatment of cognitive impairment in Parkinson’s disease.
基金supported by an under-40 grant from the Italian Association for Alzheimer’s Research [AIRALZH AGYR2021]the Strategic University Projects–Young Researcher Independence grant [YRG2021] from the Università Campus Bio-Medico di Roma (Rome, Italy)(to LLB)+1 种基金Italian Ministry of Health [Research Grant:GR-2019-12370446]the American Alzheimer’s Association [AARG-22-922961](to PK)。
文摘Despite decades of dedicated resea rch,Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disorder for which the mechanisms of onset are sti unc ear.AD is cha racterized by featured histological alterations including amyloid-beta (AB) plaque deposition,accumulation of neurofibrillary to ngles of hyperphosphorylated-tau,and neuronal loss,accompanied by progressive cognitive decline and behavioral changes.
基金supported by the National Natural Science Foundation of China(31901964)the Natural Science Foundation of Hebei,China(C2021204158)+3 种基金the Science and Technology Project of Hebei Education Department,China(BJK2022012)the Introduced Talents Project of Hebei Agricultural University,China(YJ201904)the earmarked fund for Hebei Apple Innovation Team of Modern Agroindustry Technology Research System,China(HBCT2024150205)the earmarked fund for the China Agricultural Research System,China(CARS-27).
文摘Melatonin and dopamine can potentially prevent waterlogging stress in apples.The current study investigated the mechanism by which melatonin and dopamine alleviate apple waterlogging stress.This study demonstrated that melatonin and dopamine alleviated waterlogging by removing reactive oxygen species(ROS),and that the nitric oxide(NO)content and nitrate reductase(NR)activity were significantly correlated.Melatonin and dopamine were also found to recruit different candidate beneficial endophytes(melatonin:Novosphingobium,Propionivibrio,and Cellvibrio;dopamine:Hydrogenophaga,Simplicispira,Methyloversatilis,Candidatus_Kaiserbacteria,and Humicola),and these endophytes were significantly and positively correlated with plant growth.Network analyses showed that melatonin and dopamine significantly affected the endophytic bacterial and fungal communities under waterlogging stress.The metabolomic results showed that melatonin and dopamine led to waterlogging resistance by upregulating the abundance of beneficial substances such as amino acids,flavonoids,coumarins,and organic acids.In addition,melatonin and dopamine regulated the physicochemical properties of the soil,which altered the endophyte community and affected plant growth.The co-occurrence network demonstrated close and complex relationships among endophytes,metabolites,soil,and the plants.Our results demonstrate that melatonin and dopamine alleviate waterlogging stress in apples by recruiting beneficial endophytes to enhance physiological resilience.This study provides new insights into how melatonin and dopamine alleviate stress and a theoretical basis for synergistic beneficial microbial resistance to waterlogging stress.
文摘Alzheimer's disease is a common neurodegenerative disorder in older adults.Despite its prevalence,its pathogenesis remains unclea r.In addition to the most widely accepted causes,which in clude excessive amyloid-beta aggregation,tau hyperphosphorylation,and deficiency of the neurotransmitter acetylcholine,numerous studies have shown that the dopaminergic system is also closely associated with the occurrence and development of this condition.Dopamine is a crucial catecholaminergic neurotransmitter in the human body.Dopamine-associated treatments,such as drugs that target dopamine receptor D and dopamine analogs,can improve cognitive function and alleviate psychiatric symptoms as well as ameliorate other clinical manifestations.Howeve r,therapeutics targeting the dopaminergic system are associated with various adverse reactions,such as addiction and exacerbation of cognitive impairment.This review summarizes the role of the dopaminergic system in the pathology of Alzheimer's disease,focusing on currently available dopamine-based therapies for this disorder and the common side effects associated with dopamine-related drugs.The aim of this review is to provide insights into the potential connections between the dopaminergic system and Alzheimer's disease,thus helping to clarify the mechanisms underlying the condition and exploring more effective therapeutic options.
基金Funded by the National Key Research and Development(R&D) Program of China(No.2018YFB1105702)。
文摘A novel strategy was developed to prepare the methacrylic gelatin-dopamine(GelMA-DA)/Ag nanoparticles(NPs)/graphene oxide(GO) composite hydrogels with good biocompatibility,mechanical properties,and antibacterial activity.Mussel-inspired DA was utilized to modify the GelMA molecules,which imparts good adhesive performance to the hydrogels.GO,interfacial enhancer,not only improves mechanical properties of the hydrogels,but also provides anchor sites for loading Ag NPs through numerous oxygencontaining functional groups on the surface.The experimental results show that the GelMA/Ag NPs/GO hydrogels have good biocompatibility,and exhibit a swelling rate of 202±16%,the lap shear strength of 147±17 kPa,and compressive modulus of 136±53 kPa,in the case of the Ag NPs/GO content of 2 mg/mL.Antibacterial activity of the hydrogels against both gram-negative and gram-positive bacteria is dependent on the Ag NPs/GO content derived from the release of Ag^(+).Furthermore,the GelMA/Ag NPs/GO hydrogels possess good adhesive ability,which is resistant to highly twisted state when stuck on the surface of pigskin.These results demonstrate promising potential of the GelMA-DA/Ag NPs/GO hydrogels as wound dressings for biomedical applications in clinical and emergent treatment.
基金supported by the Funding Project of Chinese Central Government Guiding to the Guangxi Local Science and Technology Development(Grant No.GUIKEZY21195021)the Natural Science Fund for Distinguished Young Scholars of Guangxi Zhuang Autonomous Region of China(Grant No.2019GXNSFFA245011)+2 种基金the Funding Project of Chinese Central Government Guiding to the Nanning Local Science and Technology Development(Grant No.20231012)the Funding Projects of Guangxi Key Research and Development Plan(GUIKE AB23075173)the Funding Project of Technological Development from Angel Yeast(Chongzuo)Co.,Ltd.(Grant No.JS1006020230722019).
文摘Dopamine can be used to treat depression,myocardial infarction,and other diseases.However,few reports are available on the de novo microbial synthesis of dopamine from low-cost substrate.In this study,integrated omics technology was used to explore the dopamine metabolism of a novel marine multi-stress-tolerant aromatic yeast Meyerozyma guilliermondii GXDK6.GXDK6 was found to have the ability to biosynthesize dopamine when using glucose as the substrate.14 key genes for the biosynthesis of dopamine were identified by whole genome-wide analysis.Transcriptomic and proteomic data showed that the expression levels of gene AAT2 encoding aspartate aminotransferase(regulating dopamine anabolism)were upregulated,while gene AO-I encoding copper amine oxidase(involved in dopamine catabolism)were downregulated under 10%NaCl stress compared with non-NaCl stress,thereby contributing to biosynthesis of dopamine.Further,the amount of dopamine under 10%NaCl stress was 2.51-fold higher than that of zero NaCl,which was consistent with the multi-omics results.Real-time fluorescence quantitative PCR(RT-qPCR)and high-performance liquid chromatography(HPLC)results confirmed the metabolic model of dopamine.Furthermore,by overexpressing AAT2,AST enzyme activity was increased by 24.89%,the expression of genes related to dopamine metabolism was enhanced,and dopamine production was increased by 56.36%in recombinant GXDK6AAT2.In conclusion,Meyerozyma guilliermondii GXDK6 could utilize low-cost carbon source to synthesize dopamine,and NaCl stress promoted the biosynthesis of dopamine.
基金supported by National Natural Science Foundation of China(31901964)the Science and Technology Project of Hebei Education Department,China(BJK2022012)+3 种基金the Innovation Ability Training Project for Graduate Student of Hebei Province,China(CXZZBS2023071)the Introduced Talents Project of Hebei Agricultural University,China(YJ201904)the Key Research and Development Project of Hebei Province,China(21326308D-02-03)the Earmarked Fund for the China Agricultural Research System,China(CARS-27).
文摘Apple replant disease(ARD)is a complex agricultural problem caused by multiple stressors that can lead to increased reactive oxygen species(ROS)levels and limited nutrient utilization in plants.However,existing countermeasures cannot effectively address this challenge.Here,we used Malus hupehensis as a test organism to investigate whether the pleiotropic molecule dopamine can alleviate ARD using pot experiments.Exogenous application of 100μmol L-1 dopamine significantly promoted the growth of apple seedlings in the replanted soil,with a relative growth rate increase of 17.44%.Our results revealed two major pathways by which dopamine regulates ARD resistance in apple trees.First,dopamine effectively reduces the level of ROS and activates the expression of genes related to nitrogen(N)transport and metabolism.Among those genes,MdNLP5,MdNRT1.1,MdNLP2,MdNRT2.5,MdNLP3,MdNRT2.4,MdNADH-GAGOT,and MdFd-GAGOT were strongly regulated by dopamine.These regulatory effects promoted the uptake and utilization of soil N by the plants.Second,dopamine improved the physical and chemical properties,enhanced microbial community diversity,and promoted mutual cooperation between microbial communities in the soil.Furthermore,dopamine altered the microbial structure of rhizosphere soil(upregulating Clostridiales,Gaiellales,Sordariales and Mortierellales;downregulating Micrococcales,Longimicrobiales,Hypocreales and Cystobasidiales).Notably,dopamine significantly upregulated the abundances of Gaiella and Mortierella,both of which were positively correlated with soil urease activity,soil available N content,plant growth and N uptake.Dopamine also significantly downregulated the abundance of the plant pathogen Gibberella(by 11.71-fold)in replant soil.Our results provide insights into the mechanisms by which dopamine promotes ARD resistance,and can promote the sustainable development of the apple industry.
基金supported by the National Natural Science Foundation of China,No.82071254(to WZ).
文摘Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia.Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia.Currently,studies have reported increased oscillation power in cases of levodopa-induced dyskinesia.However,little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced dyskinesia.Furthermore,the role of the dopamine D3 receptor,which is implicated in levodopa-induced dyskinesia,in movement disorder-related changes in neural oscillations is unclear.We found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson’s disease.Furthermore,levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components,as well as bidirectional primary motor cortex(M1)↔dorsolateral striatum gamma flow.Administration of PD128907(a selective dopamine D3 receptor agonist)induced dyskinesia and excessive gamma oscillations with a bidirectional M1↔dorsolateral striatum flow.However,administration of PG01037(a selective dopamine D3 receptor antagonist)attenuated dyskinesia,suppressed gamma oscillations and cortical gamma aperiodic components,and decreased gamma causality in the M1→dorsolateral striatum direction.These findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity,and that it has potential as a therapeutic target for levodopa-induced dyskinesia.
基金supported by the Research Project of the Shanghai Health Commission,No.2020YJZX0111(to CZ)the National Natural Science Foundation of China,Nos.82021002(to CZ),82272039(to CZ),82171252(to FL)+1 种基金a grant from the National Health Commission of People’s Republic of China(PRC),No.Pro20211231084249000238(to JW)Medical Innovation Research Project of Shanghai Science and Technology Commission,No.21Y11903300(to JG).
文摘Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism.This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism.We conducted a thorough literature search using reputable databases such as PubMed and Web of Science.Selection criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical applications.The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis.Moreover,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker.This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion.In summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.
文摘AIM:To evaluate effects of endogenous dopamine induced by low concentration atropine eye drops on choroidal neovascularization(CNV)in high myopia mice.METHODS:The C57BL/6J mice were deprived of the right eye for 4wk,and the high myopia was diagnosed by optometry,the diopter was less than-6.00 D,and CNV was induced by 532 nm laser.The changes of dopamine D1 receptor(DRD1),dopamine D2 receptor(DRD2),and vascular endothelial growth factor A(VEGFA)were detected by Western blot technology at 0.5,1,2h,and 7d after 0.01%,0.05%,and 0.1%atropine eye drops,respectively,the area of CNV was measured.RESULTS:Significant increases were observed on the expression of DRD2 in mouse high myopia model at 0.5,1,2h,7d with 0.05%and 0.1%atropine eye drops(P<0.05).Significant decreases were observed on the expression of DRD1 and VEGFA in mouse high myopia model at 0.5,1,2h,7d with 0.05%and 0.1%atropine eye drops(P<0.05).The area of CNV induced by laser in the drug-treated group was significantly smaller than that in the control group,and the higher the concentration,the more significant the inhibitory effect(P<0.05).CONCLUSION:The 0.01%,0.05%,0.1%atropine eye drops can decrease the level of VEGFA and inhibit high myopia CNV indirectly by up-regulating the level of DRD2 and down-regulating the level of DRD1,and the effect of 0.05%and 0.1%atropine eye drops is more significant.
基金supported by the National Natural Science Foundation of China,Nos. 81971006 (to DSG), 82101263 (to CXT)Jiangsu Province Science Foundation for Youths,No. BK20210903 (to CXT)+2 种基金Research Foundation for Talented Scholars of Xuzhou Medical University,No. RC20552114 (to CXT)Science&Technology Program of Xuzhou,No. KC19016 (to JC)Project of Xuzhou Medical University,No. 2018KJ06 (to JC)。
文摘Studies have found that the absence of glial cell line-derived neurotrophic factor may be the primary risk factor for Parkinson’s disease. However, there have not been any studies conducted on the potential relationship between glial cell line-derived neurotrophic factor and cognitive performance in Parkinson’s disease. We first performed a retrospective case-control study at the Affiliated Hospital of Xuzhou Medical University between September 2018 and January 2020 and found that a decreased serum level of glial cell line-derived neurotrophic factor was a risk factor for cognitive disorders in patients with Parkinson’s disease. We then established a mouse model of Parkinson’s disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and analyzed the potential relationships among glial cell line-derived neurotrophic factor in the prefrontal cortex, dopamine transmission, and cognitive function. Our results showed that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex weakened dopamine release and transmission by upregulating the presynaptic membrane expression of the dopamine transporter, which led to the loss and primitivization of dendritic spines of pyramidal neurons and cognitive impairment. In addition, magnetic resonance imaging data showed that the long-term lack of glial cell line-derived neurotrophic factor reduced the connectivity between the prefrontal cortex and other brain regions, and exogenous glial cell line-derived neurotrophic factor significantly improved this connectivity. These findings suggested that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex leads to neuroplastic degeneration at the level of synaptic connections and circuits, which results in cognitive impairment in patients with Parkinson’s disease.
文摘The^(10)boron neutron-capture therapy(BNCT)is an emerging antitumoral method that shows increasing biomedical interest.BNCT is based on the selective accumulation of the^(10)boron isotope within the tumor,which is then irradiated with low-energy thermal neutrons,generating nuclear fission that produces 7lithium,4helium,andγrays.Simple catechol-borate esters have been rather overlooked as precursors of melanin biosynthesis,and therefore,a proof-of-concept approach for using dopamine-borate(DABO)as a suitable boron-containing candidate for potential BNCT is presented here.DABO can spontaneously oxidize and autopolymerize in vitro,giving a soluble,eumelaninlike brown-black poly-DABO product.Melanotic melanoma cell cultures treated with 1 mM DABO for 24 and 48 h were viable and showed no signs of damage or cell death.The stability and possible trans-esterification of DABO is shortly discussed.Chemical calculations and quantitative structure-activity relationships(QSAR)analysis of DABO and the BNCT agent BPA indicated that they should be cell permeant and accumulate within lysosomes and melanosomes.Molecular modeling allows visualization of both the DABO precursor and the structure of a borate derivative of the proposed catechol-porphycene model for eumelanin,showing interesting features from molecular orbital calculations.The main difference between DABO and other agents,such as BPA,is that it is not a boronic acid nor a boron cluster.This simple catechol-borate ester(protected from oxidation and blackening)could be administrated to living cells and organisms,in which biosynthesis of boron-melanin in melanoma melanocytes can lead to improved BNCT.
基金This work was supported by the National Natural Science Foundation of China(No.31901964)the Science and Technology Project of Hebei Education Department(No.BJK2022012)the Earmarked fund for the China Agricultural Research System(No.CARS-27).
文摘Dopamine has demonstrated promise as a stress-relief substance.However,the function of dopamine in Cd tolerance and its mechanism remains largely unknown.The current study was performed to investigate the mechanism of dopamine on alleviating apple Cd stress through regular application of CdCl2 and dopamine solution to potting soil.The results indicated that dopamine significantly reduced reactive oxygen species(ROS)and Cd accumulation and alleviated the inhibitory effect of Cd stress on the growth of apple plants through activation of the antioxidant system,enhancement of photosynthetic capacity,and regulation of gene expression related to Cd absorption and detoxification.The richness of the rhizosphere microbial community increased,and community composition and assembly were affected by dopamine treatment.Network analysis of microbial communities showed that the numbers of nodes and total links increased significantly after dopamine treatment,while the keystone species shifted.Linear discriminant analysis effect size indicated that some biomarkers were significantly enriched after dopamine treatment,suggesting that dopamine induced plants to recruit potentially beneficial microorganisms(Pseudoxanthomonas,Aeromicrobium,Bradyrhizobium,Frankia,Saccharimonadales,Novosphingobium,and Streptomyces)to resist Cd stress.The co-occurrence network showed several metabolites that were positively correlated with relative growth rate and negatively correlated with Cd accumulation,suggesting that potentially beneficial microorganisms may be attracted by several metabolites(L-threonic acid,profenamine,juniperic acid and(3β,5ξ,9ξ)-3,6,19-trihydroxyurs-12-en-28-oic acid).Our results demonstrate that dopamine alleviates Cd stress in apple trees by recruiting beneficial microorganisms to enhance the physiological resilience revealed.This study provides an effective means to reduce the harm to agricultural production caused by heavy metals.
基金Supported by Chongqing Key Diseases Research and Application Demonstration Program,No.2019ZX003General Project of Chongqing Nature Science Foundation,No.cstc2021jcyj-msxmX0283.
文摘BACKGROUND Dopamine and cyclic adenosine monophosphate(cAMP)-regulated phosphop-rotein with an apparent Mr of 32000(DARPP-32)is a protein that is involved in regulating dopamine and cAMP signaling pathways in the brain.However,recent studies have shown that DARPP-32 is also expressed in other tissues,including colorectal cancer(CRC),where its function is not well understood.AIM To explore the effect of DARPP-32 on CRC progression.METHODS The expression levels of DARPP-32 were assessed in CRC tissues using both quantitative polymerase chain reaction and immunohistochemistry assays.The proliferative capacity of CRC cell lines was evaluated with Cell Counting Kit-8 and 5-ethynyl-2’-deoxyuridine assays,while apoptosis was measured by flow cytometry.The migratory and invasive potential of CRC cell lines were deter-mined using wound healing and transwell chamber assays.In vivo studies involved monitoring the growth rate of xenograft tumors.Finally,the underlying molecular mechanism of DARPP-32 was investigated through RNA-sequencing and western blot analyses.RESULTS DARPP-32 was frequently upregulated in CRC and associated with abnormal clinicopathological features in CRC.Overexpression of DARPP-32 was shown to promote cancer cell proliferation,migration,and invasion and reduce apoptosis.DARPP-32 knockdown resulted in the opposite functional effects.Mechanistically,DARPP-32 may regulate the phosphoinositide 3-kinase(PI3K)/AKT signaling pathway in order to carry out its biological function.CONCLUSION DARPP-32 promotes CRC progression via the PI3K/AKT signaling pathway.
文摘Pediatric autoimmune neuropsychiatric disorders associated with group A streptococcal infections (PANDAS) is a concept that is used to characterize a subset of children with neuropsychiatric symptoms, tic disorders, or obsessive-compulsive disorder (OCD), whose symptoms are exacerbated by group A streptococcal (GAS) infection. PANDAS has been known to cause a sudden onset of reward deficiency syndrome (RDS). RDS includes multiple disorders that are characterized by dopaminergic signaling dysfunction in the brain reward cascade (BRC), which may result in addiction, depression, avoidant behaviors, anxiety, tic disorders, and/or OCD. According to research by Blum et al., the dopamine receptor D2 (DRD2) gene polymorphisms are important prevalent genetic determinants of RDS. The literature demonstrates that infections like Borrelia and Lyme, as well as other infections like group A beta-hemolytic streptococcal (GABHS), can cause an autoimmune reaction and associated antibodies target dopaminergic loci in the mesolimbic region of the brain, which interferes with brain function and potentially causes RDS-like symptoms/behaviors. The treatment of PANDAS remains controversial, especially since there have been limited efficacy studies to date. We propose an innovative potential treatment for PANDAS based on previous clinical trials using a pro-dopamine regulator known as KB220 variants. Our ongoing research suggests that achieving “dopamine homeostasis” by precision-guided DNA testing and pro-dopamine modulation could result in improved therapeutic outcomes.
基金supported by the Russian Science Foundation,No.17-75-20177(to IS) and No.14-50-00069(to RRG)
文摘Dopamine (DA) is one of the brain's fundamental neurotransmitters. Despite the fact that the dopaminergic synapses constitute less than 1% of all brain synapses, DA is implicated in a number of critical physiological functions and in the pathogenesis of important psychiatric diseases such as schizophrenia, attention-deficit/hyperactivity disorder (ADHD), Parkinson's disease (PD) and others.
文摘Objective To investigate the influence of dopamine (DA) and DA receptor's antagonist on the transmission of noxious information in the central nervous system of normal rats or morphinistic rats. Methods The influence of DA on the electric activity of the pain-excited neuron (PEN) in the caudate nucleus (Cd) of normal rats or morphinistic rats was recorded after the sciatic nerve was noxiously stimulated. Results DA shortened the average latency of the evoked discharge of PEN in the Cd of normal rats, indicating that DA could increase the activity of PEN and pain sensitivity in normal rats. This effect could be inhibited by Droperidol. DA increased the average latency of the evoked discharge of PEN in the Cd of morphinistic rats, indicating that DA could inhibit the activity of PEN and pain sensitivity in morphinistic rats. Conclusion The responses to painful stimulation were completely opposite between normal rats and morphinistic rats after the intracerebroventricular injection of DA.
基金National Natural Sciences Foundation of China(Grant No.30370720and No.30572343)Nationa l973 Fundamental Project of China(No.2004CB518906)
文摘Aim To investigate the effect of liriodendrin, an extract from Fraxinus sielboldiana blume belonging to the Oleaceae family, on dopamine-induced cytotoxicity in human neuroblastoma SH-SY5Y cells. Methods Cell viability was processed when treated with 50 μmol·L^-1 of dopamine for 24 h by MTT assay. Early apoptosis, late apoptosis/necrosis were analyzed by flow cytometry using Annexin V-FITC and propidium iodide (PI) double-staining, respectively. Generation of reactive oxygen species (ROS) was assessed by DCFH-DA, an oxidation-sensitive fluorescent probe. To evaluate mitochondrion membrane potential (Δψm) using flow cytometry with the fluorescent dye Rhodamine 123. The transcriptional level of P53 was studied using RT- PCR. Results The dopamine-induced loss of cell viability was significantly attenuated by liriodendrin treatment at the concentration of 10^-8, 10^-7, 10^-6, 10^-5 and 10^-4 mol·L^-1. The protective effects of liriodendrin (10^-7, 10^-6 and 10^-5 mol·L^-1) on dopamine-induced cytotoxicity may be ascribed to its anti-oxidative properties by reducing ROS level and anti-apoptotic effect via protection of Δψm. In addition, the effect of liriodendrin may involve the P53 pathway in apoptosis. Conclusion Liriodendrin may provide a useful therapeutic strategy for the treatment of neurodegenerative diseases such as Parkinson's disease (PD)
文摘To understand the regulatory mechanisms of gonadotropin secretion in Rana rugulosa ,this study investigated the effects of dopamine (DA),estradiol (E 2) and testosterone (T) on the in vitro release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the pituitary fragments of female Rana rugulosa using a static incubation system and radio immunoassay (RIA). The results indicated that DA at the concentration from 0 1?μmol/L to 10?μmol/L inhibited the release of LH and FSH from the pituitary fragments of sexually pre mature or hibernating individuals,and the inhibitory effects enhanced with increasing concentrations of DA. E 2 at 1?μmol/L and 10?μmol/L significantly stimulated the release of LH of sexually pre mature individuals,but inhibited their FSH release at 0 1?μmol/L to 10?μmol/L;T had no obvious effects on their FSH release,but significantly inhibited their LH release at 10?μmol/L. Neither E 2 nor T,at the concentration from 0 1?μmol/L to 100?μmol/L,had obvious effects on the release of LH and FSH of hibernating individuals. The data suggest that DA and sexual steroids may have direct regulatory actions on LH and FSH release at the pituitary level in Rana rugulosa ,and the action of sexual steroids may relate to the gonadal development stages (seasons).