Background：Glehnia littoralis,as a traditional herbal medicine to heal various health ailments in East Asia,displays various therapeutic properties including antioxidant effects.However,neuroprotective effects of G.l...Background：Glehnia littoralis,as a traditional herbal medicine to heal various health ailments in East Asia,displays various therapeutic properties including antioxidant effects.However,neuroprotective effects of G.littoralis against cerebral ischemic insults have not yet been addressed.Therefore,in this study,we first examined its neuroprotective effects in the hippocampus using a gerbil model of transient global cerebral ischemia （TGCI）.Methods：Gerbils were subjected to TGCI for 5 min.G.littoralis extract （GLE;100 and 200 mg/kg） was administrated orally once daily for 7 days before ischemic surgery.Neuroprotection was examined by neuronal nuclear antigen immunohistochemistry and Fluoro-Jade B histofluorescence staining.Gliosis was observed by immunohistochemistry for glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1.For neuroprotective mechanisms,immunohistochemistry for superoxide dismutase （SOD） 1 and brain-derived neurotrophic factor （BDNF） was done.Results：Pretreatment with 200 mg/kg of GLE protected pyramidal neurons in the cornu ammonis 1 （CA1） area from ischemic insult area （F=29.770,P 〈 0.05） and significantly inhibited activationsof astrocytes （F =22.959,P 〈 0.05） and microglia （F =44.135,P 〈 0.05） in the ischemic CA1 area.In addition,pretreatment with GLE significantly increased expressions of SOD1 （F =28.561,P 〈 0.05） and BDNF （F =55.298,P 〈 0.05） in CA1 pyramidal neurons of the sham-and ischemia-operated groups.Conclusions：Our findings indicate that pretreatment with GLE can protect neurons from ischemic insults,and we suggest that its neuroprotective mechanism may be closely associated with increases of SOD 1 and BDNF expressions as well as attenuation ofglial activation.展开更多
Temporal lobe epilepsy is a multifactorial neurological dysfunction syndrome that is refractory,resistant to antiepileptic drugs,and has a high recurrence rate.The pathogenesis of temporal lobe epilepsy is complex and...Temporal lobe epilepsy is a multifactorial neurological dysfunction syndrome that is refractory,resistant to antiepileptic drugs,and has a high recurrence rate.The pathogenesis of temporal lobe epilepsy is complex and is not fully understood.Intracellular calcium dynamics have been implicated in temporal lobe epilepsy.However,the effect of fluctuating calcium activity in CA1 pyramidal neurons on temporal lobe epilepsy is unknown,and no longitudinal studies have investigated calcium activity in pyramidal neurons in the hippocampal CA1 and primary motor cortex M1 of freely moving mice.In this study,we used a multichannel fiber photometry system to continuously record calcium signals in CA1 and M1 during the temporal lobe epilepsy process.We found that calcium signals varied according to the grade of temporal lobe epilepsy episodes.In particular,cortical spreading depression,which has recently been frequently used to represent the continuously and substantially increased calcium signals,was found to correspond to complex and severe behavioral characteristics of temporal lobe epilepsy ranging from gradeⅡto gradeⅤ.However,vigorous calcium oscillations and highly synchronized calcium signals in CA1 and M1 were strongly related to convulsive motor seizures.Chemogenetic inhibition of pyramidal neurons in CA1 significantly attenuated the amplitudes of the calcium signals corresponding to gradeⅠepisodes.In addition,the latency of cortical spreading depression was prolonged,and the above-mentioned abnormal calcium signals in CA1 and M1 were also significantly reduced.Intriguingly,it was possible to rescue the altered intracellular calcium dynamics.Via simultaneous analysis of calcium signals and epileptic behaviors,we found that the progression of temporal lobe epilepsy was alleviated when specific calcium signals were reduced,and that the end-point behaviors of temporal lobe epilepsy were improved.Our results indicate that the calcium dynamic between CA1 and M1 may reflect specific epileptic behaviors corresponding t展开更多
Synapse organizers are essential for the development,transmission,and plasticity of synapses.Acting as rare synapse suppressors,the MAM domain containing glycosylphosphatidylinositol anchor(MDGA)proteins contributes t...Synapse organizers are essential for the development,transmission,and plasticity of synapses.Acting as rare synapse suppressors,the MAM domain containing glycosylphosphatidylinositol anchor(MDGA)proteins contributes to synapse organization by inhibiting the formation of the synaptogenic neuroligin-neurexin complex.A previous analysis of MDGA2 mice lacking a single copy of Mdga2 revealed upregulated glutamatergic synapses and behaviors consistent with autism.However,MDGA2 is expressed in diverse cell types and is localized to both excitatory and inhibitory synapses.Differentiating the network versus cell-specific effects of MDGA2 loss-of-function requires a cell-type and brain region-selective strategy.To address this,we generated mice harboring a conditional knockout of Mdga2 restricted to CA1 pyramidal neurons.Here we report that MDGA2 suppresses the density and function of excitatory synapses selectively on pyramidal neurons in the mature hippocampus.Conditional deletion of Mdga2 in CA1 pyramidal neurons of adult mice upregulated miniature and spontaneous excitatory postsynaptic potentials,vesicular glutamate transporter 1 intensity,and neuronal excitability.These effects were limited to glutamatergic synapses as no changes were detected in miniature and spontaneous inhibitory postsynaptic potential properties or vesicular GABA transporter intensity.Functionally,evoked basal synaptic transmission and AMPAR receptor currents were enhanced at glutamatergic inputs.At a behavioral level,memory appeared to be compromised in Mdga2 cKO mice as both novel object recognition and contextual fear conditioning performance were impaired,consistent with deficits in long-term potentiation in the CA3-CA1 pathway.Social affiliation,a behavioral analog of social deficits in autism,was similarly compromised.These results demonstrate that MDGA2 confines the properties of excitatory synapses to CA1 neurons in mature hippocampal circuits,thereby optimizing this network for plasticity,cognition,and social behaviors.展开更多
In this study, we tried to verify the neuroprotective effect of Chrysanthemum indicum Linne（CIL） extract, which has been used as a botanical drug in East Asia, against ischemic damage and to explore the underlying m...In this study, we tried to verify the neuroprotective effect of Chrysanthemum indicum Linne（CIL） extract, which has been used as a botanical drug in East Asia, against ischemic damage and to explore the underlying mechanism involving the anti-inflammatory approach. A gerbil was given CIL extract for 7 consecutive days followed by bilateral carotid artery occlusion to make a cerebral ischemia/reperfusion model. Then, we found that CIL extracts protected pyramidal neurons in the hippocampal CA1 region（CA1） from ischemic damage using neuronal nucleus immunohistochemistry and Fluoro-Jade B histofluorescence. Accordingly, interleukin-13 immunoreactivities in the CA1 pyramidal neurons of CIL-pretreated animals were maintained or increased after cerebral ischemia/reperfusion. These findings indicate that the pre-treatment of CIL can attenuate neuronal damage/death in the brain after cerebral ischemia/reperfusion via an anti-inflammatory approach.展开更多
Background Previous studies demonstrated general anesthetics affect potassium ion channels, which may be one of the mechanisms of general anesthesia. Because the effect of etomidate on potassium channels in rat hippoc...Background Previous studies demonstrated general anesthetics affect potassium ion channels, which may be one of the mechanisms of general anesthesia. Because the effect of etomidate on potassium channels in rat hippocampus which is involved in memory function has not been studied, we investigated the effects of etomidate on both delayed rectifier potassium current （IK（DR）） and transient outward potassium current （I_K（A）） in acutely dissociated rat hippocampal pyramidal neurons.Methods Single rat hippocampal pyramidal neurons from male Wistar rats of 7-10 days were acutely dissociated by enzymatic digestion and mechanical dispersion according to the methods of Kay and Wong with slight modification. Voltage-clamp recordings were performed in the whole-cell patch clamp configuration. Currents were recorded with a List EPC-10 amplifier and data were stored in a computer using Pulse 8.5. Student＇s paired two-tail t test was used for data analysis. Results At the concentration of 100 μmol/L, etomidate significantly inhibited IK（DR） by 49.2% at ＋40 mV when depolarized from -110 mV （P 〈0.01, n=8）, while did not affect IK（A） （/1=8, P 〉0.05）. The IC50value of etomidate for blocking IK（DR）was calculated as 5.4 μmol/L, with a Hill slope of 2.45. At the presence of 10 μmol/L etomidate, the V1/2 of activation curve was shifted from （17.3±1.5） mV to （10.7±9.9） mV （n=8, P 〈0.05）, the V1/2 of inactivation curve was shifted from （-18.3±2.2） mV to （-45.3±9.4） mV （n=8, P 〈0.05）. Etomidate 10 μmol/L shifted both the activation curve and inactivation curve of IK（DR））to negative potential, but mainly affected the inactivation kinetics.Conclusions Etomidate potently inhibited IK（DR） but not IK（A） in rat hippocampal pyramidal neurons. IK（DR） was inhibited by etomidate in a concentration-dependent manner, while IK（A） remained unaffected.展开更多
The axon initial segment(AIS)is a highly specialized axonal compartment where the action potential is initiated.The heterogeneity of AISs has been suggested to occur between interneurons and pyramidal neurons(PyNs),wh...The axon initial segment(AIS)is a highly specialized axonal compartment where the action potential is initiated.The heterogeneity of AISs has been suggested to occur between interneurons and pyramidal neurons(PyNs),which likely contributes to their unique spiking properties.However,whether the various characteristics of AISs can be linked to specific PyN subtypes remains unknown.Here,we report that in the prelimbic cortex(PL)of the mouse,two types of PyNs with axon projections either to the contralateral PL or to the ipsilateral basal lateral amygdala,possess distinct AIS properties reflected by morphology,ion channel expression,action potential initiation,and axo-axonic synaptic inputs from chandelier cells.Furthermore,projection-specific AIS diversity is more prominent in the superficial layer than in the deep layer.Thus,our study reveals the cortical layer-and axon projection-specific heterogeneity of PyN AISs,which may endow the spiking of various PyN types with exquisite modulation.展开更多
The tooth belongs to the trigeminal sensory pathway. Dental damage has been associated with impairments in the central nervous system that may be mediated by injury to the trigeminal nerve. In the present study, we in...The tooth belongs to the trigeminal sensory pathway. Dental damage has been associated with impairments in the central nervous system that may be mediated by injury to the trigeminal nerve. In the present study, we investigated the effects of damage to the inferior alveolar nerve, an important peripheral nerve in the trigeminal sensory pathway, on learning and memory be-haviors and structural changes in related brain regions, in a mouse model of Alzheimer’s disease. Inferior alveolar nerve transection or sham surgery was performed in middle-aged （4-month-old） or elderly （7-month-old） senescence-accelerated mouse prone 8 （SAMP8） mice. When the middle-aged mice reached 8 months （middle-aged group 1） or 11 months （middle-aged group 2）, and the elderly group reached 11 months, step-down passive avoidance and Y-maze tests of learn-ing and memory were performed, and the cholinergic system was examined in the hippocampus （Nissl staining and acetylcholinesterase histochemistry） and basal forebrain （choline acetyltrans-ferase immunohistochemistry）. In the elderly group, animals that underwent nerve transection had fewer pyramidal neurons in the hippocampal CA1 and CA3 regions, fewer cholinergic ifbers in the CA1 and dentate gyrus, and fewer cholinergic neurons in the medial septal nucleus and vertical limb of the diagonal band, compared with sham-operated animals, as well as showing impairments in learning and memory. Conversely, no signiifcant differences in histology or be-havior were observed between middle-aged group 1 or group 2 transected mice and age-matched sham-operated mice. The present ifndings suggest that trigeminal nerve damage in old age, but not middle age, can induce degeneration of the septal-hippocampal cholinergic system and loss of hippocampal pyramidal neurons, and ultimately impair learning ability. Our results highlight the importance of active treatment of trigeminal nerve damage in elderly patients and those with Alzheimer’s disease, and indicate that tooth extract展开更多
The dysfunction of the medial prefrontal cortex is associated with affective disorders and non-motor features in Parkinson’s disease.However,the exact role of the mediodorsal thalamic nucleus in the function of the p...The dysfunction of the medial prefrontal cortex is associated with affective disorders and non-motor features in Parkinson’s disease.However,the exact role of the mediodorsal thalamic nucleus in the function of the prefrontal cortex remains unclear.To study the possible effects of the mediodorsal thalamic nucleus on the neurological function of the medial prefrontal cortex,a model of Parkinson’s disease was established by injecting 8μg 6-hydroxydopamine into the substantia nigra compacta of rats.After 1 or 3 weeks,0.3μg ibotenic acid was injected into the mediodorsal thalamic nucleus of the midbrain.At 3 or 5 weeks after the initial injury,neuronal discharge in medial prefrontal cortex of rat brain was determined electrophysiologically.The numbers of dopamine-positive neurons and tyrosine hydroxylase immunoreactivity in substantia nigra compacta and ventral tegmental area were detected by immunohistochemical staining.Results demonstrated that after injury,the immunoreactivity of dopamine neurons and tyrosine hydroxylase decreased in the substantia nigra compacta and ventral tegmental areas of rats.Compared with normal medial prefrontal cortical neurons,at 3 and 5 weeks after substantia nigra compacta injury,the discharge frequency of pyramidal neurons increased and the discharge pattern of these neurons tended to be a burst-discharge,with an increased discharge interval.The discharge frequency of interneurons decreased and the discharge pattern also tended to be a burst-discharge,but the discharge interval was only higher at 3 weeks.At 3 weeks after the combined lesions,the discharge frequency,discharge pattern and discharge interval were restored to a normal level in pyramidal neurons and interneurons in medial prefrontal cortex.These findings have confirmed that mediodorsal thalamic nucleus is involved in regulating neuronal activities of the medial prefrontal cortex.The changes in the function of the mediodorsal thalamic nucleus may be associated with the abnormal discharge activity of the medial prefron展开更多
基金This research was supported by the grants from the Bio ＆ Medical Technology Development Program of the NRF funded by the Korean government, MSIP （No. NRF-2015M3A9B6066835）, and by the Bio-Synergy Research Project （No. NRF-2015M3A9C4076322） of the Ministry of Science, ICT and Future Planning, through the National Research Foundation, and by the Natural Science Foundation of Jiangsu Province of China （No. BK20140494）.
文摘Background：Glehnia littoralis,as a traditional herbal medicine to heal various health ailments in East Asia,displays various therapeutic properties including antioxidant effects.However,neuroprotective effects of G.littoralis against cerebral ischemic insults have not yet been addressed.Therefore,in this study,we first examined its neuroprotective effects in the hippocampus using a gerbil model of transient global cerebral ischemia （TGCI）.Methods：Gerbils were subjected to TGCI for 5 min.G.littoralis extract （GLE;100 and 200 mg/kg） was administrated orally once daily for 7 days before ischemic surgery.Neuroprotection was examined by neuronal nuclear antigen immunohistochemistry and Fluoro-Jade B histofluorescence staining.Gliosis was observed by immunohistochemistry for glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1.For neuroprotective mechanisms,immunohistochemistry for superoxide dismutase （SOD） 1 and brain-derived neurotrophic factor （BDNF） was done.Results：Pretreatment with 200 mg/kg of GLE protected pyramidal neurons in the cornu ammonis 1 （CA1） area from ischemic insult area （F=29.770,P 〈 0.05） and significantly inhibited activationsof astrocytes （F =22.959,P 〈 0.05） and microglia （F =44.135,P 〈 0.05） in the ischemic CA1 area.In addition,pretreatment with GLE significantly increased expressions of SOD1 （F =28.561,P 〈 0.05） and BDNF （F =55.298,P 〈 0.05） in CA1 pyramidal neurons of the sham-and ischemia-operated groups.Conclusions：Our findings indicate that pretreatment with GLE can protect neurons from ischemic insults,and we suggest that its neuroprotective mechanism may be closely associated with increases of SOD 1 and BDNF expressions as well as attenuation ofglial activation.
基金supported by the National Natural Science Foundation of China,Nos.62027812(to HS),81771470(to HS),and 82101608(to YL)Tianjin Postgraduate Research and Innovation Project,No.2020YJSS122(to XD)。
文摘Temporal lobe epilepsy is a multifactorial neurological dysfunction syndrome that is refractory,resistant to antiepileptic drugs,and has a high recurrence rate.The pathogenesis of temporal lobe epilepsy is complex and is not fully understood.Intracellular calcium dynamics have been implicated in temporal lobe epilepsy.However,the effect of fluctuating calcium activity in CA1 pyramidal neurons on temporal lobe epilepsy is unknown,and no longitudinal studies have investigated calcium activity in pyramidal neurons in the hippocampal CA1 and primary motor cortex M1 of freely moving mice.In this study,we used a multichannel fiber photometry system to continuously record calcium signals in CA1 and M1 during the temporal lobe epilepsy process.We found that calcium signals varied according to the grade of temporal lobe epilepsy episodes.In particular,cortical spreading depression,which has recently been frequently used to represent the continuously and substantially increased calcium signals,was found to correspond to complex and severe behavioral characteristics of temporal lobe epilepsy ranging from gradeⅡto gradeⅤ.However,vigorous calcium oscillations and highly synchronized calcium signals in CA1 and M1 were strongly related to convulsive motor seizures.Chemogenetic inhibition of pyramidal neurons in CA1 significantly attenuated the amplitudes of the calcium signals corresponding to gradeⅠepisodes.In addition,the latency of cortical spreading depression was prolonged,and the above-mentioned abnormal calcium signals in CA1 and M1 were also significantly reduced.Intriguingly,it was possible to rescue the altered intracellular calcium dynamics.Via simultaneous analysis of calcium signals and epileptic behaviors,we found that the progression of temporal lobe epilepsy was alleviated when specific calcium signals were reduced,and that the end-point behaviors of temporal lobe epilepsy were improved.Our results indicate that the calcium dynamic between CA1 and M1 may reflect specific epileptic behaviors corresponding t
基金supported by the National Natural Science Foundation of China(No.31571098,32071026)Shanghai Municipal Science and Technology Major Project(No.2018SHZDZX01)+1 种基金ZJ LabShanghai Center for Brain Science and Brain-Inspired Technology。
基金supported by the National Natural Science Foundation of China(82001203,82173819,81871012,and 81571263)the Scientific Research Fund of Zhejiang Provincial Education Department(Y201839276)+3 种基金the Scientific Research Foundation of Zhejiang University City College(X-202103)the R&D Project of Zhejiang(2022C03034)the Natural Science Foundation of Zhejiang Province(LQ23C090001)a Canada Research Chair Award(P2018-0246).
文摘Synapse organizers are essential for the development,transmission,and plasticity of synapses.Acting as rare synapse suppressors,the MAM domain containing glycosylphosphatidylinositol anchor(MDGA)proteins contributes to synapse organization by inhibiting the formation of the synaptogenic neuroligin-neurexin complex.A previous analysis of MDGA2 mice lacking a single copy of Mdga2 revealed upregulated glutamatergic synapses and behaviors consistent with autism.However,MDGA2 is expressed in diverse cell types and is localized to both excitatory and inhibitory synapses.Differentiating the network versus cell-specific effects of MDGA2 loss-of-function requires a cell-type and brain region-selective strategy.To address this,we generated mice harboring a conditional knockout of Mdga2 restricted to CA1 pyramidal neurons.Here we report that MDGA2 suppresses the density and function of excitatory synapses selectively on pyramidal neurons in the mature hippocampus.Conditional deletion of Mdga2 in CA1 pyramidal neurons of adult mice upregulated miniature and spontaneous excitatory postsynaptic potentials,vesicular glutamate transporter 1 intensity,and neuronal excitability.These effects were limited to glutamatergic synapses as no changes were detected in miniature and spontaneous inhibitory postsynaptic potential properties or vesicular GABA transporter intensity.Functionally,evoked basal synaptic transmission and AMPAR receptor currents were enhanced at glutamatergic inputs.At a behavioral level,memory appeared to be compromised in Mdga2 cKO mice as both novel object recognition and contextual fear conditioning performance were impaired,consistent with deficits in long-term potentiation in the CA3-CA1 pathway.Social affiliation,a behavioral analog of social deficits in autism,was similarly compromised.These results demonstrate that MDGA2 confines the properties of excitatory synapses to CA1 neurons in mature hippocampal circuits,thereby optimizing this network for plasticity,cognition,and social behaviors.
基金supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Science,ICT and Future Planning(NRF-2013R1A2A2A01068190)Hallym University Specialization Fund(HRF-S-13)
文摘In this study, we tried to verify the neuroprotective effect of Chrysanthemum indicum Linne（CIL） extract, which has been used as a botanical drug in East Asia, against ischemic damage and to explore the underlying mechanism involving the anti-inflammatory approach. A gerbil was given CIL extract for 7 consecutive days followed by bilateral carotid artery occlusion to make a cerebral ischemia/reperfusion model. Then, we found that CIL extracts protected pyramidal neurons in the hippocampal CA1 region（CA1） from ischemic damage using neuronal nucleus immunohistochemistry and Fluoro-Jade B histofluorescence. Accordingly, interleukin-13 immunoreactivities in the CA1 pyramidal neurons of CIL-pretreated animals were maintained or increased after cerebral ischemia/reperfusion. These findings indicate that the pre-treatment of CIL can attenuate neuronal damage/death in the brain after cerebral ischemia/reperfusion via an anti-inflammatory approach.
基金This study was supported by a grant from the National Nature Science Foundation of China （No. 30672030）.
文摘Background Previous studies demonstrated general anesthetics affect potassium ion channels, which may be one of the mechanisms of general anesthesia. Because the effect of etomidate on potassium channels in rat hippocampus which is involved in memory function has not been studied, we investigated the effects of etomidate on both delayed rectifier potassium current （IK（DR）） and transient outward potassium current （I_K（A）） in acutely dissociated rat hippocampal pyramidal neurons.Methods Single rat hippocampal pyramidal neurons from male Wistar rats of 7-10 days were acutely dissociated by enzymatic digestion and mechanical dispersion according to the methods of Kay and Wong with slight modification. Voltage-clamp recordings were performed in the whole-cell patch clamp configuration. Currents were recorded with a List EPC-10 amplifier and data were stored in a computer using Pulse 8.5. Student＇s paired two-tail t test was used for data analysis. Results At the concentration of 100 μmol/L, etomidate significantly inhibited IK（DR） by 49.2% at ＋40 mV when depolarized from -110 mV （P 〈0.01, n=8）, while did not affect IK（A） （/1=8, P 〉0.05）. The IC50value of etomidate for blocking IK（DR）was calculated as 5.4 μmol/L, with a Hill slope of 2.45. At the presence of 10 μmol/L etomidate, the V1/2 of activation curve was shifted from （17.3±1.5） mV to （10.7±9.9） mV （n=8, P 〈0.05）, the V1/2 of inactivation curve was shifted from （-18.3±2.2） mV to （-45.3±9.4） mV （n=8, P 〈0.05）. Etomidate 10 μmol/L shifted both the activation curve and inactivation curve of IK（DR））to negative potential, but mainly affected the inactivation kinetics.Conclusions Etomidate potently inhibited IK（DR） but not IK（A） in rat hippocampal pyramidal neurons. IK（DR） was inhibited by etomidate in a concentration-dependent manner, while IK（A） remained unaffected.
基金supported by the National Natural Science Foundation of China(82071450,31972903,and 32000681)Shanghai Pujiang Program(20PJ1401000)+3 种基金the Natural Science Foundation of Shanghai(20ZR1405700)Shanghai Municipal Science and Technology Major Project(No.2018SHZDZX01)ZJ Lab,the Shanghai Center for Brain Science and Brain-Inspired Technologythe Fudan Undergraduate Research Opportunities Program(Wangdao 20046).
文摘The axon initial segment(AIS)is a highly specialized axonal compartment where the action potential is initiated.The heterogeneity of AISs has been suggested to occur between interneurons and pyramidal neurons(PyNs),which likely contributes to their unique spiking properties.However,whether the various characteristics of AISs can be linked to specific PyN subtypes remains unknown.Here,we report that in the prelimbic cortex(PL)of the mouse,two types of PyNs with axon projections either to the contralateral PL or to the ipsilateral basal lateral amygdala,possess distinct AIS properties reflected by morphology,ion channel expression,action potential initiation,and axo-axonic synaptic inputs from chandelier cells.Furthermore,projection-specific AIS diversity is more prominent in the superficial layer than in the deep layer.Thus,our study reveals the cortical layer-and axon projection-specific heterogeneity of PyN AISs,which may endow the spiking of various PyN types with exquisite modulation.
基金supported by the National Natural Science Foundation of China,No.81371107,81470760the Natural Science Foundation of Guangdong Province in China,No.S2013010015888+1 种基金the Foundation of Open Laboratory of Sun Yat-sen University in China,No.KF201312a grant from Translational Medicine Center,Guangdong Department of Science&Technology,No.2011A080300002
文摘The tooth belongs to the trigeminal sensory pathway. Dental damage has been associated with impairments in the central nervous system that may be mediated by injury to the trigeminal nerve. In the present study, we investigated the effects of damage to the inferior alveolar nerve, an important peripheral nerve in the trigeminal sensory pathway, on learning and memory be-haviors and structural changes in related brain regions, in a mouse model of Alzheimer’s disease. Inferior alveolar nerve transection or sham surgery was performed in middle-aged （4-month-old） or elderly （7-month-old） senescence-accelerated mouse prone 8 （SAMP8） mice. When the middle-aged mice reached 8 months （middle-aged group 1） or 11 months （middle-aged group 2）, and the elderly group reached 11 months, step-down passive avoidance and Y-maze tests of learn-ing and memory were performed, and the cholinergic system was examined in the hippocampus （Nissl staining and acetylcholinesterase histochemistry） and basal forebrain （choline acetyltrans-ferase immunohistochemistry）. In the elderly group, animals that underwent nerve transection had fewer pyramidal neurons in the hippocampal CA1 and CA3 regions, fewer cholinergic ifbers in the CA1 and dentate gyrus, and fewer cholinergic neurons in the medial septal nucleus and vertical limb of the diagonal band, compared with sham-operated animals, as well as showing impairments in learning and memory. Conversely, no signiifcant differences in histology or be-havior were observed between middle-aged group 1 or group 2 transected mice and age-matched sham-operated mice. The present ifndings suggest that trigeminal nerve damage in old age, but not middle age, can induce degeneration of the septal-hippocampal cholinergic system and loss of hippocampal pyramidal neurons, and ultimately impair learning ability. Our results highlight the importance of active treatment of trigeminal nerve damage in elderly patients and those with Alzheimer’s disease, and indicate that tooth extract
基金supported by the Key Research Project of Science and Technology of Henan Province of China,No.14B180007(to LLF)the Development Project of Science and Technology of Luoyang Municipality of China,No.1401087A-5(to LLF)
文摘The dysfunction of the medial prefrontal cortex is associated with affective disorders and non-motor features in Parkinson’s disease.However,the exact role of the mediodorsal thalamic nucleus in the function of the prefrontal cortex remains unclear.To study the possible effects of the mediodorsal thalamic nucleus on the neurological function of the medial prefrontal cortex,a model of Parkinson’s disease was established by injecting 8μg 6-hydroxydopamine into the substantia nigra compacta of rats.After 1 or 3 weeks,0.3μg ibotenic acid was injected into the mediodorsal thalamic nucleus of the midbrain.At 3 or 5 weeks after the initial injury,neuronal discharge in medial prefrontal cortex of rat brain was determined electrophysiologically.The numbers of dopamine-positive neurons and tyrosine hydroxylase immunoreactivity in substantia nigra compacta and ventral tegmental area were detected by immunohistochemical staining.Results demonstrated that after injury,the immunoreactivity of dopamine neurons and tyrosine hydroxylase decreased in the substantia nigra compacta and ventral tegmental areas of rats.Compared with normal medial prefrontal cortical neurons,at 3 and 5 weeks after substantia nigra compacta injury,the discharge frequency of pyramidal neurons increased and the discharge pattern of these neurons tended to be a burst-discharge,with an increased discharge interval.The discharge frequency of interneurons decreased and the discharge pattern also tended to be a burst-discharge,but the discharge interval was only higher at 3 weeks.At 3 weeks after the combined lesions,the discharge frequency,discharge pattern and discharge interval were restored to a normal level in pyramidal neurons and interneurons in medial prefrontal cortex.These findings have confirmed that mediodorsal thalamic nucleus is involved in regulating neuronal activities of the medial prefrontal cortex.The changes in the function of the mediodorsal thalamic nucleus may be associated with the abnormal discharge activity of the medial prefron
