Adult neurogenesis persists after birth in the subventricular zone, with new neurons migrating to the granule cell layer and glomerular layers of the olfactory bulb, where they integrate into existing circuitry as inh...Adult neurogenesis persists after birth in the subventricular zone, with new neurons migrating to the granule cell layer and glomerular layers of the olfactory bulb, where they integrate into existing circuitry as inhibitory interneurons. The generation of these new neurons in the olfactory bulb supports both structural and functional plasticity, aiding in circuit remodeling triggered by memory and learning processes. However, the presence of these neurons, coupled with the cellular diversity within the olfactory bulb, presents an ongoing challenge in understanding its network organization and function. Moreover,the continuous integration of new neurons in the olfactory bulb plays a pivotal role in regulating olfactory information processing. This adaptive process responds to changes in epithelial composition and contributes to the formation of olfactory memories by modulating cellular connectivity within the olfactory bulb and interacting intricately with higher-order brain regions. The role of adult neurogenesis in olfactory bulb functions remains a topic of debate. Nevertheless, the functionality of the olfactory bulb is intricately linked to the organization of granule cells around mitral and tufted cells. This organizational pattern significantly impacts output, network behavior, and synaptic plasticity, which are crucial for olfactory perception and memory. Additionally, this organization is further shaped by axon terminals originating from cortical and subcortical regions. Despite the crucial role of olfactory bulb in brain functions and behaviors related to olfaction, these complex and highly interconnected processes have not been comprehensively studied as a whole. Therefore, this manuscript aims to discuss our current understanding and explore how neural plasticity and olfactory neurogenesis contribute to enhancing the adaptability of the olfactory system. These mechanisms are thought to support olfactory learning and memory, potentially through increased complexity and restructuring of neural network structures, as well as the addition of new granule granule cells that aid in olfactory adaptation. Additionally, the manuscript underscores the importance of employing precise methodologies to elucidate the specific roles of adult neurogenesis amidst conflicting data and varying experimental paradigms. Understanding these processes is essential for gaining insights into the complexities of olfactory function and behavior.展开更多
A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigati...A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.展开更多
Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic nerve.Still,it is unknown whether olfactory enshea...Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic nerve.Still,it is unknown whether olfactory ensheathing glia also have neuroprotective properties.Olfactory ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion cells.Therefore,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve crush.Olfactory ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive treatments.Anatomical and gene expression analyses were performed.Olfactory bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡmolecules.Allogeneically and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an epimembrane.In axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 days.In these retinas,microglial anatomical activation was higher than after optic nerve crush alone.In intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or immunosuppression.However,neuroprotection of axotomized retinal ganglion cells did not improve with these treatments.The different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.展开更多
Changes in olfactory function are considered to be early biomarkers of Parkinson’s disease.Olfactory dysfunction is one of the earliest non-motor features of Parkinson’s disease,appearing in about 90%of patients wit...Changes in olfactory function are considered to be early biomarkers of Parkinson’s disease.Olfactory dysfunction is one of the earliest non-motor features of Parkinson’s disease,appearing in about 90%of patients with early-stage Parkinson’s disease,and can often predate the diagnosis by years.Therefore,olfactory dysfunction should be considered a reliable marker of the disease.However,the mechanisms responsible for olfactory dysfunction are currently unknown.In this article,we clearly explain the pathology and medical definition of olfactory function as a biomarker for early-stage Parkinson’s disease.On the basis of the findings of clinical olfactory function tests and animal model experiments as well as neurotransmitter expression levels,we further characterize the relationship between olfactory dysfunction and neurodegenerative diseases as well as the molecular mechanisms underlying olfactory dysfunction in the pathology of early-stage Parkinson’s disease.The findings highlighted in this review suggest that olfactory dysfunction is an important biomarker for preclinical-stage Parkinson’s disease.Therefore,therapeutic drugs targeting non-motor symptoms such as olfactory dysfunction in the early stage of Parkinson’s disease may prevent or delay dopaminergic neurodegeneration and reduce motor symptoms,highlighting the potential of identifying effective targets for treating Parkinson’s disease by inhibiting the deterioration of olfactory dysfunction.展开更多
A highly sensitive olfactory system allows insects to precisely identify and position volatile compounds from different sources in their habitats,and plays a crucial role in their foraging,mating,and oviposition activ...A highly sensitive olfactory system allows insects to precisely identify and position volatile compounds from different sources in their habitats,and plays a crucial role in their foraging,mating,and oviposition activities.During evolution,insects have successfully developed a large and complex olfactory system to adapt to heterogeneous environments,enabling the maintenance of inset population.A comprehensive examination of the olfactory system of insects may therefore yield novel insights into the development of innovative pest control and prevention strategies,as well as the study of olfactory mechanisms in vertebrates and even humans.This paper outlines the current state of research into the signal transduction mechanism by which insects perceive the olfactory molecules of their habitats.The aim of this review is to provide a reference point for future studies into the olfactory perception mechanism and its potential applications in pest management.展开更多
Objective Combine olfactory ensheathing glia (OEG) implantation with ex vivo non-viral vector-based neurotrophin- 3 (NT-3) gene therapy in attempting to enhance regeneration after thoracic spinal cord injury (SCI...Objective Combine olfactory ensheathing glia (OEG) implantation with ex vivo non-viral vector-based neurotrophin- 3 (NT-3) gene therapy in attempting to enhance regeneration after thoracic spinal cord injury (SCI). Methods Primary OEG were transfected with cationic liposome-mediated recombinant plasmid pcDNA3.1 (+)-NT3 and subsequently implanted into adult Wistar rats directly after the thoracic spinal cord (T9) contusion by the New York University impactor. The animals in 3 different groups received 4x 1050EG transfected with pcDNA3.1 (+)-NT3 or pcDNA3.1 (+) plasmids, or the OEGs without any plasmid transfection, respectively; the fourth group was untreated group, in which no OEG was implanted. Results NT-3 production was seen increased both ex vivo and in vivo in pcDNA3.1 (+)-NT3 transfected OEGs. Three months after implantation of NT-3-transfected OEGs, behavioral analysis revealed that the hindlimb function of SCI rats was improved. All spinal cords were filled with regenerated neurofilament-positive axons. Retrograde tracing revealed enhanced regenerative axonal sprouting. Conclusion Non-viral vector-mediated genetic engineering of OEG was safe and more effective in producing NT- 3 and promoting axonal outgrowth followed by enhancing SCI recovery in rats.展开更多
[ Objective ] With Cupressustorulosa, Cinnamomum camphora and Cyclobalanopsis Oerst as test materials, the paper studied the effects of different non- host plants on olfactory responses of Tomicus yunnanensis. [ Metho...[ Objective ] With Cupressustorulosa, Cinnamomum camphora and Cyclobalanopsis Oerst as test materials, the paper studied the effects of different non- host plants on olfactory responses of Tomicus yunnanensis. [ Method ] The needles of Pinus yunnanensis were mixed with the leaves of Cupressustondosa, C. cam- phora and C. Oerst according to the ratios of 0 g : 6 g, 1 g : 5 g, 2 g : 4 g, 3 g : 3 g, 4 g : 2 g, 5 g : 1 g and 6 g : 0 g, and the mixtures were put in the re- spanse arm of Y-tube olfactometer as odor source to observe the olfactory behavior of T. yunnanensis, the empty arm was set as control. [ Result ] When the needles of P. yunnanensis were mixed with the leaves of non-hest plants according to the ratio of 1 g : 5 g and 2 g : 4 g, they had less difference on attractive rate to T. yun- nanensis compared with complete P. yunnanensis needles in mixture (ratio: 6 g : 0 g), and the maximum difference was 14%. When the needles ofP. yunnanen- sis were mixed with non-host leaves according to the ratio of 1 g : 5 g, 2 g : 4 g, the attractive rate to T. yunnanensis decreased compared with complete P. yun- nanensis needles in mixture ( ratio: 6 g : 0 g), and the decrease value in maximum was 40%. [ Conclusion] When the ratio of non-host plants was relatively small in mixed leaves, non-host had less impact on olfactory responses of T. yunnanensis. As the proportion of non-hest leaves gradually increased, the attractive rate of leaf mixtures to T. yunnanensis was gradually small. The results could provide reference for determination of mixed ratio in construction of mixed forest and the de- velopment of botanical attractive and repellent of T. yunnanensis.展开更多
The purpose of this article is to detect sex and age difference in the structure of the olfactory bulb in dogs by histological methods. The thickness of the olfactory bulbs layers and its main cells were analyzed comp...The purpose of this article is to detect sex and age difference in the structure of the olfactory bulb in dogs by histological methods. The thickness of the olfactory bulbs layers and its main cells were analyzed comparatively with the methods of HE-staining and statistics, through which we studied the development course of dogs' olfactory bulb and the structural differences which affect the olfaction in both males and females. The results showed that between both male and female juveniles and adult males and females, the difference in thickness of each layer is not significant. But the difference in quantity of mitral cells between adult males and females was significant. Meanwhile, the structure of every layer in juvenile dogs was apparent while the volume and the weight of adult dogs' olfactory bulb and each layer's width increased significantly. On the other hand, the density of each layer's cells decreased apparently. Our results demonstrated that the olfactory bulb developed with age, and the apparent differences in morphology and quantity of mitral cells between males and females may be one of the reasons leading to the sexual variations of olfactory sensitivity.展开更多
Objective] The aim of this study was to investigate the electrophysiological characteristics of spontaneous electrical activities of olfactory bulb in Bufo gargarizans during postembryonic development. [Method] Microe...Objective] The aim of this study was to investigate the electrophysiological characteristics of spontaneous electrical activities of olfactory bulb in Bufo gargarizans during postembryonic development. [Method] Microelectrode technique was used to record extracellular spontaneous electrical activities of olfactory bulb in B. gar-garizans. [Result] Along with the development of olfactory bulb, the discharge types increased gradual y. Single spontaneous firing enhanced gradual y and it reached the maximum in the metamorphosis phase. The intensity of consecutive single sponta-neous firing changed slightly at the middle of post-embryonic development, but it was stil higher than in the early phase and the adult phase. Consecutive burst spontaneous firing frequency went down over time. [Conclusion] Along with the de-velopment of olfactory bulb, the neuronal excitability increases step by step and the neuronal electrical activities diversify gradualy.展开更多
Objective To investigate the effects of combined transplantation of neural stem cells (NSC) and olfactory ensheathing cells (OEC) on the motor function of rats with intracerebral hemorrhage. Methods In three days ...Objective To investigate the effects of combined transplantation of neural stem cells (NSC) and olfactory ensheathing cells (OEC) on the motor function of rats with intracerebral hemorrhage. Methods In three days after a rat model of caudate nucleus hemorrhage was established, NSCs and OEC, NSC, OEC (from embryos of Wistar rats) or normal saline were injected into bematomas of rats in combined transplantation group, NSC group, OEC group, and control group, respectively. Damage of neural function was scored before and in 3, 7, 14, 30 days after operation. Tissue after transplantation was observed by immunocytochemistry staining. Results The scores for the NSC, OEC and co-transplantation groups were significantly lower in 14 and 30 days after operation than in 3 days after operation (P〈0.05). The scores for the NSC and OEC groups were significantly lower than those for the control group only in 30 days after operation (P〈0.05), while the difference for the NSC-OEC group was significant in 14 days after operation (P〈0.05). Immunocytochemistry staining revealed that the transplanted OEC and NSC could survive, migrate and differentiate into neurons, astrocytes, and oligodendrocytes. The number of neural precursor cells was greater in the NSC and combined transplantation groups than in the control group. The number of neurons differentiated from NSC was significantly greater in the co-transplantation group than in the NSC group. Conclusion Co-transplantation of NSC and OEC can promote the repair of injured tissue and improve the motor fimction of rats with intracerebral hemorrhage.展开更多
Forty-three patients with chronic spinal cord injury for over 6 months were transplanted with bryonic olfactory ensheathing cells, 2-4 × 106, into multiple sites in the injured area under the sur-gical microscope...Forty-three patients with chronic spinal cord injury for over 6 months were transplanted with bryonic olfactory ensheathing cells, 2-4 × 106, into multiple sites in the injured area under the sur-gical microscope. The sympathetic skin response in patients was measured with an electromyo-graphy/evoked potential instrument 1 day before transplantation and 3-8 weeks after trans-tion. Spinal nerve function of patients was assessed using the American Spinal Injury Association impairment scale. The sympathetic skin response was elicited in 32 cases before olfactory en-sheathing celltransplantation, while it was observed in 34 cases after transplantation. tantly, sympathetic skin response latency decreased significantly and amplitude increased cantly after transplantation. Transplantation of olfactory ensheathing cells also improved American Spinal Injury Association scores for movement, pain and light touch. Our findings indicate that factory ensheathing celltransplantation improves motor, sensory and autonomic nerve functions in patients with chronic spinal cord injury.展开更多
The main active components extracted from Panax notoginseng are total saponins. They have been shown to inhibit platelet aggregation, increase cerebral blood flow, improve neurological behavior, decrease infarct volum...The main active components extracted from Panax notoginseng are total saponins. They have been shown to inhibit platelet aggregation, increase cerebral blood flow, improve neurological behavior, decrease infarct volume and promote proliferation and differentiation of neural stem cells in the hippocampus and lateral ventricles. However, there is a lack of studies on whether total saponins of Panax notoginsertg have potential benefits on immature neuroblasts in the olfactory bulb following ischemia and reperfusion. This study established a rat model of global cerebral ischemia and reperfusion using four-vessel occlusion. Rats were administered total sa- ponins of Panax notoginseng at 75 mg/kg intraperitoneally 30 minutes after ischemia then once a day, for either 7 or 14 days. Total saponins of Panax notoginseng enhanced the number of dou- blecortin (DCX)+ neural progenitor ceils and increased co-localization of DCX with neuronal nuclei and phosphorylated cAMP response element-binding/DCX+ neural progenitor cells in the olfactory bulb at 7 and 14 days post ischemia. These findings indicate that following global brain ischemia/reperfusion, total saponins of Panax notoginseng promote differentiation of DCX+ cells expressing immature neuroblasts in the olfactory bulb and the underlying mechanism is related to the activation of the signaling pathway of cyclic adenosine monophosphate response element binding protein.展开更多
BACKGROUND: It has been demonstrated that the transplantation of olfactory ensheathing cell (OEC) can promote the recovery of neurological function through ameliorating the local internal environment in spinal cord...BACKGROUND: It has been demonstrated that the transplantation of olfactory ensheathing cell (OEC) can promote the recovery of neurological function through ameliorating the local internal environment in spinal cord injury. OBJECTIVE: To evaluate the recent efficacy of OEC transplantation on old spinal cord injury. DESIGN: A self-controlled experiment. SETTING: Department ofNeurosurgery, Taian Rongjun Hospital of Shandong Province. PARTICIPANTS: Totally 106 inpatients with old spinal cord injury were selected from the Department of Neurosurgery, Taian Rongjun Hospital of Shandong Province from June 2004 to December 2006, including 97 males and 9 females. Inclusive criteria: ① Complete data; ② Informed with the fact; ③No further recover neurological function after drug therapy (neurotrophic factor, GM-1), traditional Chinese medicine, physiotherapy and rehabilitative exercises; ④ No obvious compression of the injured spinal cord displayed by MRI examination. METHODS: ① The olfactory bulb was obtained from embryo of induced labor in middle pregnancy above 4 months supplied voluntarily by pregnant women, and the survived cells after purification and culture for 1 - 2 weeks were collected. Dura mater was incised by posterior approach, then the cultured OEC suspension was transplanted to corresponding regions by means of multi-target injection using microscope. ② The patients were evaluated for twice with the standards suggested by American Spinal Injury Association (ASIA) at admission and 2 - 4 weeks postoperatively, in order to investigate the efficacy in different age groups, different sites and at different time points after the OEC transplantation. ③ Standards for evaluation: The International Standard for Neurological and Functional Classification of Spinal Cord Injury set by ASIA: The highest score of motor function was 100 points; The highest score of sensory function was 112 points for light touch and 112 for acupuncture sense. Frankel grading modified by ASIA in 1992: grades A, B, C, D and E (grade A for complete injury, and grade E for normal). ④ The data were statistically processed by Professor Cheng from the Department of Statistics, Taishan Medical College. MAIN OUTCOME MEASURES: Changes of motor and sensory functions postoperatively. RESULTS: All the 106 patients with old spinal cord injury were involved in the analysis of results. Grade A (n =72) at admission recovered to grade B in 31 cases and grade C in 7 cases after operation; Grade B (n =9) recovered to grade C in 2 cases; Grade C (n =15) recovered to grade D in 4 cases; Grade D (n =10) recovered to grade E in 1 cases, which referred to normal sensory and motor functions. The scores of motor, tactile sensation and pain sensation postoperatively were all obviously higher than those at admission (t =5.381, 7.036, 7.775, P 〈 0.05). The recovery of motor function had obvious difference among patients of different ages (F =5.235, P =0.001). There were no obvious differences in the recovery of motor and sensory functions among patients of different sexes, courses, injured types and sites. CONCLUSION: The neurological function can be ameliorated in a short time after OEC transplantation in patients with old spinal cord injury. The efficacy is generally the same in patients of different sexes, courses, injured types and sites, but there are differences in the effects on motor function of patients of different ages.展开更多
文摘Adult neurogenesis persists after birth in the subventricular zone, with new neurons migrating to the granule cell layer and glomerular layers of the olfactory bulb, where they integrate into existing circuitry as inhibitory interneurons. The generation of these new neurons in the olfactory bulb supports both structural and functional plasticity, aiding in circuit remodeling triggered by memory and learning processes. However, the presence of these neurons, coupled with the cellular diversity within the olfactory bulb, presents an ongoing challenge in understanding its network organization and function. Moreover,the continuous integration of new neurons in the olfactory bulb plays a pivotal role in regulating olfactory information processing. This adaptive process responds to changes in epithelial composition and contributes to the formation of olfactory memories by modulating cellular connectivity within the olfactory bulb and interacting intricately with higher-order brain regions. The role of adult neurogenesis in olfactory bulb functions remains a topic of debate. Nevertheless, the functionality of the olfactory bulb is intricately linked to the organization of granule cells around mitral and tufted cells. This organizational pattern significantly impacts output, network behavior, and synaptic plasticity, which are crucial for olfactory perception and memory. Additionally, this organization is further shaped by axon terminals originating from cortical and subcortical regions. Despite the crucial role of olfactory bulb in brain functions and behaviors related to olfaction, these complex and highly interconnected processes have not been comprehensively studied as a whole. Therefore, this manuscript aims to discuss our current understanding and explore how neural plasticity and olfactory neurogenesis contribute to enhancing the adaptability of the olfactory system. These mechanisms are thought to support olfactory learning and memory, potentially through increased complexity and restructuring of neural network structures, as well as the addition of new granule granule cells that aid in olfactory adaptation. Additionally, the manuscript underscores the importance of employing precise methodologies to elucidate the specific roles of adult neurogenesis amidst conflicting data and varying experimental paradigms. Understanding these processes is essential for gaining insights into the complexities of olfactory function and behavior.
基金supported by the National Natural Science Foundation of China,No.82001155(to LL)the Natural Science Foundation of Zhejiang Province,No.LY23H090004(to LL)+5 种基金the Natural Science Foundation of Ningbo,No.2023J068(to LL)the Fundamental Research Funds for the Provincial Universities of Zhejiang Province,No.SJLY2023008(to LL)the College Students'Scientific and Technological Innovation Project(Xin Miao Talent Plan)of Zhejiang Province,No.2022R405A045(to CC)the Student ResearchInnovation Program(SRIP)of Ningbo University,Nos.20235RIP1919(to CZ),2023SRIP1938(to YZ)the K.C.Wong Magna Fund in Ningbo University。
文摘A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.
基金supported by the Spanish Ministry of Economy and Competitiveness,No.PID2019-106498GB-I00(to MVS)the Instituto de Salud CarlosⅢ,Fondo Europeo de Desarrollo Regional“Una manera de hacer Europa”,No.PI19/00071(to MAB)+1 种基金Ministerio de Ciencia e Innovación Project,No.SAF2017-82736-C2-1-R(to MTMF)in Universidad Autónoma de MadridFundación Universidad Francisco de Vitoria(to JS)。
文摘Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic nerve.Still,it is unknown whether olfactory ensheathing glia also have neuroprotective properties.Olfactory ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion cells.Therefore,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve crush.Olfactory ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive treatments.Anatomical and gene expression analyses were performed.Olfactory bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡmolecules.Allogeneically and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an epimembrane.In axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 days.In these retinas,microglial anatomical activation was higher than after optic nerve crush alone.In intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or immunosuppression.However,neuroprotection of axotomized retinal ganglion cells did not improve with these treatments.The different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.
基金supported by the National Natural Science Foundation of China,No.82104421the China Postdoctoral Science Foundation,No.2022M721726+1 种基金the Innovation and Entrepreneurship Training Program for College Students of Jiangsu Province,No.202210304155Ythe Research Startup Fund Program of Nantong University,No.135421623023(all to XZ).
文摘Changes in olfactory function are considered to be early biomarkers of Parkinson’s disease.Olfactory dysfunction is one of the earliest non-motor features of Parkinson’s disease,appearing in about 90%of patients with early-stage Parkinson’s disease,and can often predate the diagnosis by years.Therefore,olfactory dysfunction should be considered a reliable marker of the disease.However,the mechanisms responsible for olfactory dysfunction are currently unknown.In this article,we clearly explain the pathology and medical definition of olfactory function as a biomarker for early-stage Parkinson’s disease.On the basis of the findings of clinical olfactory function tests and animal model experiments as well as neurotransmitter expression levels,we further characterize the relationship between olfactory dysfunction and neurodegenerative diseases as well as the molecular mechanisms underlying olfactory dysfunction in the pathology of early-stage Parkinson’s disease.The findings highlighted in this review suggest that olfactory dysfunction is an important biomarker for preclinical-stage Parkinson’s disease.Therefore,therapeutic drugs targeting non-motor symptoms such as olfactory dysfunction in the early stage of Parkinson’s disease may prevent or delay dopaminergic neurodegeneration and reduce motor symptoms,highlighting the potential of identifying effective targets for treating Parkinson’s disease by inhibiting the deterioration of olfactory dysfunction.
基金Supported by China Agriculture Research System of MOF and MARA(CARS-26)Innovation Platform Construction Project of Zhaoqing University(202413004)+1 种基金Innovation and Entrepreneurship Training Program Project of Guangdong Province College Student(X202310580113)Scientific Research Fund Funding Project of Zhaoqing University in 2023(QN202331).
文摘A highly sensitive olfactory system allows insects to precisely identify and position volatile compounds from different sources in their habitats,and plays a crucial role in their foraging,mating,and oviposition activities.During evolution,insects have successfully developed a large and complex olfactory system to adapt to heterogeneous environments,enabling the maintenance of inset population.A comprehensive examination of the olfactory system of insects may therefore yield novel insights into the development of innovative pest control and prevention strategies,as well as the study of olfactory mechanisms in vertebrates and even humans.This paper outlines the current state of research into the signal transduction mechanism by which insects perceive the olfactory molecules of their habitats.The aim of this review is to provide a reference point for future studies into the olfactory perception mechanism and its potential applications in pest management.
文摘Objective Combine olfactory ensheathing glia (OEG) implantation with ex vivo non-viral vector-based neurotrophin- 3 (NT-3) gene therapy in attempting to enhance regeneration after thoracic spinal cord injury (SCI). Methods Primary OEG were transfected with cationic liposome-mediated recombinant plasmid pcDNA3.1 (+)-NT3 and subsequently implanted into adult Wistar rats directly after the thoracic spinal cord (T9) contusion by the New York University impactor. The animals in 3 different groups received 4x 1050EG transfected with pcDNA3.1 (+)-NT3 or pcDNA3.1 (+) plasmids, or the OEGs without any plasmid transfection, respectively; the fourth group was untreated group, in which no OEG was implanted. Results NT-3 production was seen increased both ex vivo and in vivo in pcDNA3.1 (+)-NT3 transfected OEGs. Three months after implantation of NT-3-transfected OEGs, behavioral analysis revealed that the hindlimb function of SCI rats was improved. All spinal cords were filled with regenerated neurofilament-positive axons. Retrograde tracing revealed enhanced regenerative axonal sprouting. Conclusion Non-viral vector-mediated genetic engineering of OEG was safe and more effective in producing NT- 3 and promoting axonal outgrowth followed by enhancing SCI recovery in rats.
基金Supported by 948 Project of State Forestry Administration(2009-4-38)~~
文摘[ Objective ] With Cupressustorulosa, Cinnamomum camphora and Cyclobalanopsis Oerst as test materials, the paper studied the effects of different non- host plants on olfactory responses of Tomicus yunnanensis. [ Method ] The needles of Pinus yunnanensis were mixed with the leaves of Cupressustondosa, C. cam- phora and C. Oerst according to the ratios of 0 g : 6 g, 1 g : 5 g, 2 g : 4 g, 3 g : 3 g, 4 g : 2 g, 5 g : 1 g and 6 g : 0 g, and the mixtures were put in the re- spanse arm of Y-tube olfactometer as odor source to observe the olfactory behavior of T. yunnanensis, the empty arm was set as control. [ Result ] When the needles of P. yunnanensis were mixed with the leaves of non-hest plants according to the ratio of 1 g : 5 g and 2 g : 4 g, they had less difference on attractive rate to T. yun- nanensis compared with complete P. yunnanensis needles in mixture (ratio: 6 g : 0 g), and the maximum difference was 14%. When the needles ofP. yunnanen- sis were mixed with non-host leaves according to the ratio of 1 g : 5 g, 2 g : 4 g, the attractive rate to T. yunnanensis decreased compared with complete P. yun- nanensis needles in mixture ( ratio: 6 g : 0 g), and the decrease value in maximum was 40%. [ Conclusion] When the ratio of non-host plants was relatively small in mixed leaves, non-host had less impact on olfactory responses of T. yunnanensis. As the proportion of non-hest leaves gradually increased, the attractive rate of leaf mixtures to T. yunnanensis was gradually small. The results could provide reference for determination of mixed ratio in construction of mixed forest and the de- velopment of botanical attractive and repellent of T. yunnanensis.
基金National Natural Science Foundation of China (30370218)Shan-dong Science Fund for Distinguished Young Scholars(2005BS02005)Science Foundation for Excellent Scholars of Ministry of Education of China (NCET-07-0507)
文摘The purpose of this article is to detect sex and age difference in the structure of the olfactory bulb in dogs by histological methods. The thickness of the olfactory bulbs layers and its main cells were analyzed comparatively with the methods of HE-staining and statistics, through which we studied the development course of dogs' olfactory bulb and the structural differences which affect the olfaction in both males and females. The results showed that between both male and female juveniles and adult males and females, the difference in thickness of each layer is not significant. But the difference in quantity of mitral cells between adult males and females was significant. Meanwhile, the structure of every layer in juvenile dogs was apparent while the volume and the weight of adult dogs' olfactory bulb and each layer's width increased significantly. On the other hand, the density of each layer's cells decreased apparently. Our results demonstrated that the olfactory bulb developed with age, and the apparent differences in morphology and quantity of mitral cells between males and females may be one of the reasons leading to the sexual variations of olfactory sensitivity.
基金Supported by grants from the Liaoning Provincial Department of Education(2011196)the Experimental Center Director Fund of Shenyang Normal University(sy201003)~~
文摘Objective] The aim of this study was to investigate the electrophysiological characteristics of spontaneous electrical activities of olfactory bulb in Bufo gargarizans during postembryonic development. [Method] Microelectrode technique was used to record extracellular spontaneous electrical activities of olfactory bulb in B. gar-garizans. [Result] Along with the development of olfactory bulb, the discharge types increased gradual y. Single spontaneous firing enhanced gradual y and it reached the maximum in the metamorphosis phase. The intensity of consecutive single sponta-neous firing changed slightly at the middle of post-embryonic development, but it was stil higher than in the early phase and the adult phase. Consecutive burst spontaneous firing frequency went down over time. [Conclusion] Along with the de-velopment of olfactory bulb, the neuronal excitability increases step by step and the neuronal electrical activities diversify gradualy.
基金supported by the National Natural Science Foundation of China (30570628 & 30770751)
文摘Objective To investigate the effects of combined transplantation of neural stem cells (NSC) and olfactory ensheathing cells (OEC) on the motor function of rats with intracerebral hemorrhage. Methods In three days after a rat model of caudate nucleus hemorrhage was established, NSCs and OEC, NSC, OEC (from embryos of Wistar rats) or normal saline were injected into bematomas of rats in combined transplantation group, NSC group, OEC group, and control group, respectively. Damage of neural function was scored before and in 3, 7, 14, 30 days after operation. Tissue after transplantation was observed by immunocytochemistry staining. Results The scores for the NSC, OEC and co-transplantation groups were significantly lower in 14 and 30 days after operation than in 3 days after operation (P〈0.05). The scores for the NSC and OEC groups were significantly lower than those for the control group only in 30 days after operation (P〈0.05), while the difference for the NSC-OEC group was significant in 14 days after operation (P〈0.05). Immunocytochemistry staining revealed that the transplanted OEC and NSC could survive, migrate and differentiate into neurons, astrocytes, and oligodendrocytes. The number of neural precursor cells was greater in the NSC and combined transplantation groups than in the control group. The number of neurons differentiated from NSC was significantly greater in the co-transplantation group than in the NSC group. Conclusion Co-transplantation of NSC and OEC can promote the repair of injured tissue and improve the motor fimction of rats with intracerebral hemorrhage.
文摘Forty-three patients with chronic spinal cord injury for over 6 months were transplanted with bryonic olfactory ensheathing cells, 2-4 × 106, into multiple sites in the injured area under the sur-gical microscope. The sympathetic skin response in patients was measured with an electromyo-graphy/evoked potential instrument 1 day before transplantation and 3-8 weeks after trans-tion. Spinal nerve function of patients was assessed using the American Spinal Injury Association impairment scale. The sympathetic skin response was elicited in 32 cases before olfactory en-sheathing celltransplantation, while it was observed in 34 cases after transplantation. tantly, sympathetic skin response latency decreased significantly and amplitude increased cantly after transplantation. Transplantation of olfactory ensheathing cells also improved American Spinal Injury Association scores for movement, pain and light touch. Our findings indicate that factory ensheathing celltransplantation improves motor, sensory and autonomic nerve functions in patients with chronic spinal cord injury.
基金supported by the Hunan Provincial Innovation Foundation for Postgraduate in China,No.CX2014B099(to XH)the Science Foundation of Hunan Provincial Education Department of China,No.11C1264(to FJD),13C958(to XH)
文摘The main active components extracted from Panax notoginseng are total saponins. They have been shown to inhibit platelet aggregation, increase cerebral blood flow, improve neurological behavior, decrease infarct volume and promote proliferation and differentiation of neural stem cells in the hippocampus and lateral ventricles. However, there is a lack of studies on whether total saponins of Panax notoginsertg have potential benefits on immature neuroblasts in the olfactory bulb following ischemia and reperfusion. This study established a rat model of global cerebral ischemia and reperfusion using four-vessel occlusion. Rats were administered total sa- ponins of Panax notoginseng at 75 mg/kg intraperitoneally 30 minutes after ischemia then once a day, for either 7 or 14 days. Total saponins of Panax notoginseng enhanced the number of dou- blecortin (DCX)+ neural progenitor ceils and increased co-localization of DCX with neuronal nuclei and phosphorylated cAMP response element-binding/DCX+ neural progenitor cells in the olfactory bulb at 7 and 14 days post ischemia. These findings indicate that following global brain ischemia/reperfusion, total saponins of Panax notoginseng promote differentiation of DCX+ cells expressing immature neuroblasts in the olfactory bulb and the underlying mechanism is related to the activation of the signaling pathway of cyclic adenosine monophosphate response element binding protein.
文摘BACKGROUND: It has been demonstrated that the transplantation of olfactory ensheathing cell (OEC) can promote the recovery of neurological function through ameliorating the local internal environment in spinal cord injury. OBJECTIVE: To evaluate the recent efficacy of OEC transplantation on old spinal cord injury. DESIGN: A self-controlled experiment. SETTING: Department ofNeurosurgery, Taian Rongjun Hospital of Shandong Province. PARTICIPANTS: Totally 106 inpatients with old spinal cord injury were selected from the Department of Neurosurgery, Taian Rongjun Hospital of Shandong Province from June 2004 to December 2006, including 97 males and 9 females. Inclusive criteria: ① Complete data; ② Informed with the fact; ③No further recover neurological function after drug therapy (neurotrophic factor, GM-1), traditional Chinese medicine, physiotherapy and rehabilitative exercises; ④ No obvious compression of the injured spinal cord displayed by MRI examination. METHODS: ① The olfactory bulb was obtained from embryo of induced labor in middle pregnancy above 4 months supplied voluntarily by pregnant women, and the survived cells after purification and culture for 1 - 2 weeks were collected. Dura mater was incised by posterior approach, then the cultured OEC suspension was transplanted to corresponding regions by means of multi-target injection using microscope. ② The patients were evaluated for twice with the standards suggested by American Spinal Injury Association (ASIA) at admission and 2 - 4 weeks postoperatively, in order to investigate the efficacy in different age groups, different sites and at different time points after the OEC transplantation. ③ Standards for evaluation: The International Standard for Neurological and Functional Classification of Spinal Cord Injury set by ASIA: The highest score of motor function was 100 points; The highest score of sensory function was 112 points for light touch and 112 for acupuncture sense. Frankel grading modified by ASIA in 1992: grades A, B, C, D and E (grade A for complete injury, and grade E for normal). ④ The data were statistically processed by Professor Cheng from the Department of Statistics, Taishan Medical College. MAIN OUTCOME MEASURES: Changes of motor and sensory functions postoperatively. RESULTS: All the 106 patients with old spinal cord injury were involved in the analysis of results. Grade A (n =72) at admission recovered to grade B in 31 cases and grade C in 7 cases after operation; Grade B (n =9) recovered to grade C in 2 cases; Grade C (n =15) recovered to grade D in 4 cases; Grade D (n =10) recovered to grade E in 1 cases, which referred to normal sensory and motor functions. The scores of motor, tactile sensation and pain sensation postoperatively were all obviously higher than those at admission (t =5.381, 7.036, 7.775, P 〈 0.05). The recovery of motor function had obvious difference among patients of different ages (F =5.235, P =0.001). There were no obvious differences in the recovery of motor and sensory functions among patients of different sexes, courses, injured types and sites. CONCLUSION: The neurological function can be ameliorated in a short time after OEC transplantation in patients with old spinal cord injury. The efficacy is generally the same in patients of different sexes, courses, injured types and sites, but there are differences in the effects on motor function of patients of different ages.