How dopamine tunes parvalbumin interneurons in the hippocampus:new experimental observations in Alzheimer's disease

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.

Context-dependency in medicine:how neuronal excitability influences the impact of dopamine on cognition

Dopamine,often termed the"feel-good"neurotransmitter,plays a crucial role in myriad physiological and psychological brain processes.While dopamine is primarily associated with pleasure,reward,and motivation,its effects can be quite complex;and this complexity is further compounded when examining how dopamine functions in typical versus disease-affected neural circuits.In pa rticula r,epilepsy,characte rized by heightened brain excitability,is linked to cognitive dysfunction,and dopamine is implicated in elements of both its pathology and treatment.Neuroscience has been successful in describing the synaptic abnormalities believed to contribute to memory issues in epilepsy,aiding in the search for effective therapies for what persists as a major medical issue.

The dopaminergic system and Alzheimer's disease

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.

Cortico-striatal gamma oscillations are modulated by dopamine D3 receptors in dyskinetic rats

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.

Recent progress in the applications of presynaptic dopaminergic positron emission tomography imaging in 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.

The roles of serine protease, intracellular and extracellular phenoloxidase in activation of prophenoloxidase system, and characterization of phenoloxidase from shrimp haemocytes induced by lipopolysaccharide or dopamine

We investigated the effects of lipopolysaccharide （LPS） and dopamine （DA） on the activation of the prophenoloxidase （proPO） system of Litopenaeus vannamei. LPS and DA were shown with a negative dose-dependent effect on hyalne cells （HC）, semi-granular cells （SGC）, large granular cells （LGC）, and total haemocyte count （THC）. When haemocytes were treated with LPS or DA, serine proteinase activity and intracellular phenoloxidase （PO） activity were significantly reduced, but extracellular PO activity increased significantly. These findings indicated that the reduction in haemocyte counts was mainly because of the degranulation and activation of the proPO system from semi-granule and large granule cells. The PKC inhibitor, chelerythrine, and the TPK inhibitor, genistein, had an inhibitory effect on extracellular PO activity, while serine proteinase and intracellular PO activity increased. This suggests that the LPS and DA induce the activation of proPO in haemocytes via PKC and TPK-related signaling pathways, but serine proteinase may be activated only by PKC, as the genistein effects were not statistically significant. Electrophoresis analysis revealed that POs induced by LPS or DA have the same molecular mass and high diphenolase activity. Two PO bands at 526 kDa and 272 kDa were observed in PAGE, while in the haemocyte lysate supematant （HLS）, only a 272-kDa band was observed. This band was resolved after SDS-PAGE under non-reducing and reducing conditions into two groups of POs, 166 kDa and 126 kDa, and 78.1 kDa and 73.6 kDa, respectively, suggesting that PO in L. vannamei is an oligomer, which may have different compositions intra- and extracellularly.

Iron contributes to the formation of catechol isoquinolines and oxidative toxicity induced by overdose dopamine in dopaminergic SH-SY5Y cells

Objective The selective loss of dopaminergic neurons in Parkinson＇s disease is suspected to correlate with the increase of cellular iron, which may be involved in the pathogenesis of PD by promotion of oxidative stress. This research investigated dopamine-induced oxidative stress toxicity contributed by iron and the production of dopamine-derived neurotoxins in dopaminergic SH-SYSY cells. Methods After the SH-SYSY cells were pre-incubated with dopamine and Fe^2＋ for 24 h, the cell viability, hydroxyl radical, melondialdehyde, cell apoptosis, and catechol isoquinolines were measured by lactate dehydrogenase assay, salicylic acid trapping method, thiobarbuteric acid assay, Hoechst 33258 staining and HPLC-electrochemical detection （HPLC-ECD）, respectively. Results （1） Optimal dopamine （150 μmol/L） and Fe^2＋ （40 or 80 μmol/L） significantly increased the concentrations of hydroxy radicals and melondialdehyde in SH-SYSY cells. （2） Induction with dopamine alone or dopamine and Fe^2＋ （dopamine/Fe^2＋） caused cell apoptosis. （3） Compared with untreated cells, the catechol isoquinolines, salsolinol and N-methyl-salsolinol in dopamine/Fe^2＋-induced cells were detected in increasing amounts. Conclusion Due to dopamine/Fe^2＋-induced oxidative stress similar to the state in the parkinsonian substantia nigra neurons, dopamine and Fe^2＋ impaired SH-SYSY cells could be used as the cell oxidative stress model of Parkinson＇s disease. The catechol isoquinolines detected in cells may be involved in the pathogenesis of Parkinson＇s disease as potential neurotoxins.

Dopamine in the prefrontal cortex plays multiple roles in the executive function of patients with Parkinson's disease

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.

Hippocampal dopamine as a key regulator for learning deficits in Parkinson's disease

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.

Cobalt phthalocyanine-graphene complex for electro-catalytic oxidation of dopamine

Cobalt phthalocyanine-graphene （CoPc-Gr） complex are fabricated through 7r-Tr interaction of each components, with CoPc adsorbed/inserted on/in the graphene sheets. The obtained complex could be used in the electro-chemical detection of various medicines. CoPc-Gr modified glassy electrode shows excellent response to the electro-oxidation of dopamine （DA） and ascorbic acid （AA）, much better than those of CoPc, graphene oxide （GrO） or graphene （Gr） modified electrode. Significantly, the detection of dopamine is a diffusion-controlled process, highly selective, and has a low detection limit and broad linear range.

Electrocatalytic Oxidation and Simultaneous Determination of Uric Acid,Xanthine,Hypoxanthine and Dopamine Based on β-Cyclodextrin Modified Glassy Carbon Electrode

A novel covalently modified glassy carbon electrode with β-cyclodextrin was prepared via electropolymerization technique for the simultaneous determination of uric acid（UA）,xanthine（XA）,hypoxanthine（HX） and dopamine（DA）.This new electrode presented an excellent electrocatalytic activity towards the oxidation of UA,XA,HX and DA by cyclic voltammetry（CV） method.The oxidation peaks of the four compounds were well defined and had the enhanced peak currents.The separation potentials of the oxidation peaks for DA-UA,UA-XA and XA-HX were 150,390 and 360 mV in CV,respectively.By means of differential pulse voltammetry（DPV） method,the calibration curves in the ranges of 10―225,5―105,10―170 and 5―150 μmol/L were obtained for UA,XA,HX and DA,respectively.The lowest detection limits（S/N=3） were 5,1.25,5 and 1.5 μmol/L for UA,XA,HX and DA,respectively.The practical application of the modified electrode was demonstrated by the determination of DA in hydrochloride injection and UA,XA,HX in human urine samples.

Neuroprotective effects of tadalafil on gerbil dopaminergic neurons following cerebral ischemia

Impairment of dopamine function, which is known to have major effects on behaviors and cognition, is one of the main problems associated with cerebral ischemia. Tadalafil, a long-acting phosphodiesterase type-5 inhibitor, is known to ameliorate neurologic impairment induced by brain injury, but not in dopaminergic regions. We investigated the neuroprotective effects of treatment with tadalafil on cyclic guanosine monophosphate level and dopamine function following cerebral ischemia. Forty adult Mongolian gerbils were randomly and evenly divided into five groups （n = 8 in each group）： Sham-operation group, cerebral ischemia-induced and 0, 0.1, 1, and 10 mg/kg tadalafil-treated groups, respectively. Tadalafil dissolved in distilled water was administered orally for 7 consecutive days, starting 1 day after surgery. Cyclic guanosine monophosphate assay and immunohistochemistry were performed for thyrosine hydroxylase expression and western blot analysis for dopamine D2 receptor expression. A decrease in cyclic guanosine monophosphate level following cerebral ischemia was found with an increase in thyrosine hydroxylase activity and a decrease in dopamine D2 receptor expression in the striatum and substantia nigra region. However, treatment with tadalafil increased cyclic guanosine monophosphate expression, suppressed thyrosine hydroxylase expression and increased dopamine 92 receptor expression in the striatum and substantia nigra region in a dose-dependent manner. Tadalafil might ameliorate cerebral ischemia-induced dopaminergic neuron injury. Therefore, tadalafil has the potential as a new neuroprotective treatment strategy for cerebral ischemic injury.

Melatonin and dopamine alleviate waterlogging stress in apples by recruiting beneficial endophytes to enhance physiological resilience

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.

Effect of Dopamine Injection on the Hemocyte Count and Prophenoloxidase System of the White Shrimp Litopenaeus vannamei

Effects of dopamine injection on the hemocyte count, phenoloxidase activity, serine proteinase activity, proteinase in-hibitor activity and α2-macroglobulin-like activity in L. vannamei were studied. Results showed that dopamine injection resulted in a significant effect on the parameters measured (P < 0.05), while no significant difference was observed in the control group (0.85% NaCl). In the experimental groups,the hemocyte count reached the minimum in 3 h;granular and semi-granular cells became stable after 12 h and hyaline cells and the total hemocyte count became stable after 18 h. Phenoloxidase activity reached the minimum in 6 h, and then became stable after 9 h. Serine protease activity and proteinase inhibitor activity reached the minimum in 3 h, and α2-macro-globulin-like activity reached the maximum in 3 h,and all the three parameters became stable after 12 h. The results suggest that the activating mechanisms of the proPO system triggered by dopamine are different from those triggered by invasive agents or sponta-neously activated under a normal physical condition.

Effects of endogenous dopamine induced by low concentration atropine eye drops on choroidal neovascularization in high myopia mice

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.

Effect of Aqueous Extract of <i>Phoenix dactylifera</i>Pollen on Dopamine System of Nucleus Accumbens in Male Rats

Background: Dopamine has been known to facilitate male sexual function. Methods: The effect of aqueous extract (140 mg/kg) of Phoenix dactylifera date palm pollen on sexual behavior and determining of dopamine transmission in the nucleus accumbens was studied in male rats using in vivo microdialysis. Results: Releasing of dopamine increased significantly in the nucleus accumbens when a receptive female was introduced behind a screen (p 0.001). During copulation, dopamine increased markedly in control and treated rats. Phoenix dactylifera Date Palm Pollen enhanced the orientation of males towards females by increasing mounting and ano-genital investigatory behavior. Improving of sexual behavior and dopamine release was higher in treated rats in comparison with control (p 0.001). Conclusion: These results indicate a neurochemical basis for interaction between dopaminergic agents and male sexual behavior. Therefore, Phoenix dactylifera Date Palm Pollen seems to act as a dopamine agonist and to cure male infertility. It can be used as an aphrodisiac that leads to further increases in dopamine release.

Mussel-inspired Methacrylic Gelatin-dopamine/Ag Nanoparticles/Graphene Oxide Hydrogels with Improved Adhesive and Antibacterial Properties for Applications as Wound Dressings

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.

Diabetes mellitus and Parkinson's disease:dangerous liaisons between insulin and dopamine

The relationship between diabetes mellitus and Parkinson's disease has been described in several epidemiological studies over the 1960 s to date.Molecular studies have shown the possible functional link between insulin and dopamine,as there is strong evidence demonstrating the action of dopamine in pancreatic islets,as well as the insulin effects on feeding and cognition through central nervous system mechanism,largely independent of glucose utilization.Therapies used for the treatment of type 2 diabetes mellitus appear to be promising candidates for symptomatic and/or disease-modifying action in neurodegenerative diseases including Parkinson's disease,while an old dopamine agonist,bromocriptine,has been repositioned for the type 2 diabetes mellitus treatment.This review will aim at reappraising the different studies that have highlighted the dangerous liaisons between diabetes mellitus and Parkinson's disease.

Degree of dopaminergic degeneration measured by ^(99m)Tc-TRODAT-1 SPECT/CT imaging

To prevent and treat Parkinson＇s disease in its early stages,it is essential to be able to detect the degree of early dopaminergic neuron degeneration.Dopamine transporters（DAT） in the striatum regulate synaptic dopamine levels,and striatal ^99mTc-TRODAT-1 single-photon emission computed tomography（-SPECT） imaging is a marker for presynaptic neuronal degeneration.However,the association between the degree of dopaminergic degeneration and in vivo ^99mTc-TRODAT-1 SPECT imaging is unknown.Therefore,this study investigated the association between the degree of 6-hydroxydopamine（6-OHDA）-induced dopaminergic degeneration and DAT imaging using^99mTc-TRODAT-1 SPECT in rats.Different degrees of nigrostriatal dopamine depletion were generated by injecting different doses of 6-OHDA（2,4,and 8 μg） into the right medial forebrain bundle.The degree of nigrostriatal dopaminergic neuron degeneration was assessed by rotational behavior and immunohistochemical staining.The results showed that striatal ^99mTc-TRODAT-1 binding was significantly diminished both in the ipsilateral and the contralateral sides in the 4 and 8 μg 6-OHDA groups,and that DAT ^99mTc-TRODAT-1 binding in the ipsilateral striatum showed a high correlation to apomorphine-induced rotations at 8 weeks post-lesion（r = –0.887,P 〈 0.01）.There were significant correlations between DAT ^99mTc-TRODAT-1 binding in the ipsilateral striatum and the amount of tyrosine hydroxylase immunoreactive neurons in the ipsilateral substantia nigra in the 2,4,and 8 μg 6-OHDA groups at 8 weeks post-lesion（r = 0.899,P 〈 0.01）.These findings indicate that striatal DAT imaging using ^99mTc-TRODAT-1 is a useful technique for evaluating the severity of dopaminergic degeneration.

Dopamine improves apple replant disease resistance by regulating physiological resilience and rhizosphere microbial community structure

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.