Cognitive impairment is the most common complication in patients with temporal lobe epilepsy with hippocampal scle rosis.There is no effective treatment for cognitive impairment.Medial septum cholinergic neurons have ...Cognitive impairment is the most common complication in patients with temporal lobe epilepsy with hippocampal scle rosis.There is no effective treatment for cognitive impairment.Medial septum cholinergic neurons have been reported to be a potential target for controlling epileptic seizures in tempo ral lobe epile psy.However,their role in the cognitive impairment of temporal lobe epilepsy remains unclear.In this study,we found that patients with temporal lobe epile psy with hippocampal sclerosis had a low memory quotient and severe impairment in verbal memory,but had no impairment in nonverbal memory.The cognitive impairment was slightly correlated with reduced medial septum volume and medial septum-hippocampus tra cts measured by diffusion tensor imaging.In a mouse model of chronic temporal lobe epilepsy induced by kainic acid,the number of medial septum choline rgic neurons was reduced and acetylcholine release was reduced in the hippocampus.Furthermore,selective apoptosis of medial septum cholinergic neurons mimicked the cognitive deficits in epileptic mice,and activation of medial septum cholinergic neurons enhanced hippocampal acetylcholine release and restored cognitive function in both kainic acid-and kindling-induced epile psy models.These res ults suggest that activation of medial septum cholinergic neurons reduces cognitive deficits in temporal lobe epilepsy by increasing acetylcholine release via projections to the hippocampus.展开更多
BACKGROUND： It has beenshown that ginsenoside, the effective component of ginseng, can enhance expression of choline acetyl transferase, as well as brain-derived neurotrophic factor （BDNF） and its receptor tyrosine...BACKGROUND： It has beenshown that ginsenoside, the effective component of ginseng, can enhance expression of choline acetyl transferase, as well as brain-derived neurotrophic factor （BDNF） and its receptor tyrosine kinase B （TrkB）, in cholinergic neurons of the basal forebrain. OBJECTIVE： To qualitatively and quantitatively verify the influence of ginsenoside on expression of BDNF and its receptor, TrkB, in the medial septum of aged rats, and to provide a molecular basis for clinical application. DESIGN~ TIME AND SETTING： A contrast study, which was performed in the Department of Anatomy, China Medical University, and the Department of Anatomy, Shenyang Medical College between December 2005 and May 2007. MATERIALS： Thirty-five, healthy, female, Sprague Dawley rats were selected for this study. Ginsenoside （81% purity） was provided by Jilin Ji＇an Wantai Chinese Medicine Factory; anti-BDNF antibody, anti-TrkB antibody, and their kits were provided by Wuhan Boster Company. METHODS： A total of 35 rats were divided into three groups： young （four months old）, aging （26 months old）, and ginsenoside. Rats in the ginsenoside group were administered ginsenoside （25 mg/kg/d） between 17 months and 26 months. MAIN OUTCOME MEASURES： Immunohistochemistry and in situ hybridization were used to measure expression of BDNF and TrkB in the medial septum of aged rats, and the detected results were expressed as gray values. RESULTS： （1） Qualitative detection： using microscopy, degenerative neurons were visible in the medial septum in the aging group. However, neuronal morphology in the ginsenoside group was similar to neurons in the young group. （2） Quantitative detection： the mean gray value of BDNF-positive and TrkB-positive products in the aging group were significantly higher than in the young group （t = 3.346, 4.169, P 〈 0.01）; however, the mean gray value in the ginsenoside group was significantly lower than in the aging group （t = 2.432, 2.651, P 〈 0.01）. CONCLUSION： Ginsenoside can increase expression of BDNF and TrkB in the medial septum and delay the natural degeneration in aged rats.展开更多
Olfactory bulbectomy (OBX) causes cognitive dysfunction by degeneration of cholinergic neurons in the medial septum. Here, we define an involvement of nicotinic acetylcholine receptor (nAChR) in neuroprotective effect...Olfactory bulbectomy (OBX) causes cognitive dysfunction by degeneration of cholinergic neurons in the medial septum. Here, we define an involvement of nicotinic acetylcholine receptor (nAChR) in neuroprotective effect of donepezil in the septum neurons of OBX mice. Neuroprotective effects on the medial septal cholinergic neurons were assessed after chronic donepezil administration in OBX mice. We also measured Akt and ERK phosphorylation to define the neuroprotective mechanism of donepezil. We found that treatment with donepezil (1 - 3 mg/kg) for 15 consecutive days completely rescued cholinergic neurons in the OBX mice with concomitant improved memory. Reduction of both protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) phosphorylation were restored by chronic donepezil administration (1 - 3 mg/kg) in OBX mouse medial septum. Both phosphorylated Akt and ERK immunoreactivities were localized in cell bodies of choline acetyltransferase (ChAT)-positive cholinergic cells in the medial septum. Enhancement of Akt and ERK phosphorylation seen following donepezil administration was totally blocked by pre-administration of mecamylamine (10 μM), a nicotinic acetylcholine receptor antagonist. Donepezil increases phosphorylation of Akt and ERK via nAChR stimulation in the medial septum cholinergic neurons. The Akt and ERK stimulation by donepezil is associated with its ability of neuroprotection in the medial septum and memory improvement.展开更多
目的探讨内侧隔斜角带复合体(medial septum-diagonal band of Broca complex,MS-DB)中5-HT1A受体在帕金森病(Parkinson's disease,PD)认知功能中的作用及机制。方法以6-羟基多巴胺(6-hydroxydopamine,6-OHDA)损毁单侧内侧前脑束(me...目的探讨内侧隔斜角带复合体(medial septum-diagonal band of Broca complex,MS-DB)中5-HT1A受体在帕金森病(Parkinson's disease,PD)认知功能中的作用及机制。方法以6-羟基多巴胺(6-hydroxydopamine,6-OHDA)损毁单侧内侧前脑束(medial forebrain bundle,MFB)的PD模型大鼠为对象,采用行为学和电生理学方法,观察激活或阻断MS-DB中5-HT1A受体对PD认知功能和海马theta节律的影响。结果 (1)单侧MFB损毁降低了大鼠在T-迷宫实验中的选择正确率,MS-DB局部注射5-HT1A受体激动剂8-OH-DPAT进一步降低模型组大鼠在T-迷宫实验中的选择正确率,而MS-DB局部注射选择性5-HT1A受体拮抗剂WAY100635升高模型组大鼠的选择正确率;(2)单侧MFB损毁使海马theta节律的峰频率降低,MS-DB局部注射8-OH-DPAT抑制海马theta节律,降低theta节律的标准化功率,而MS-DB局部注射WAY100635诱发海马theta节律,并使theta节律的标准化功率升高。结论阻断MS-DB中的5-HT1A受体可改善模型组大鼠的工作记忆,这可能是通过兴奋海马theta节律来实现的。展开更多
基金National Natural Science Foundation of China,Nos.82003 729 (to Ying W),82022071 (to YiW)Natural Science Foundation of Shandong Province of China,No.ZR2020QH357 (to Ying W)Public Welfare Technology Research Program of Zhejiang Province,No.LGF20H09001 1 (to JF)。
文摘Cognitive impairment is the most common complication in patients with temporal lobe epilepsy with hippocampal scle rosis.There is no effective treatment for cognitive impairment.Medial septum cholinergic neurons have been reported to be a potential target for controlling epileptic seizures in tempo ral lobe epile psy.However,their role in the cognitive impairment of temporal lobe epilepsy remains unclear.In this study,we found that patients with temporal lobe epile psy with hippocampal sclerosis had a low memory quotient and severe impairment in verbal memory,but had no impairment in nonverbal memory.The cognitive impairment was slightly correlated with reduced medial septum volume and medial septum-hippocampus tra cts measured by diffusion tensor imaging.In a mouse model of chronic temporal lobe epilepsy induced by kainic acid,the number of medial septum choline rgic neurons was reduced and acetylcholine release was reduced in the hippocampus.Furthermore,selective apoptosis of medial septum cholinergic neurons mimicked the cognitive deficits in epileptic mice,and activation of medial septum cholinergic neurons enhanced hippocampal acetylcholine release and restored cognitive function in both kainic acid-and kindling-induced epile psy models.These res ults suggest that activation of medial septum cholinergic neurons reduces cognitive deficits in temporal lobe epilepsy by increasing acetylcholine release via projections to the hippocampus.
文摘BACKGROUND： It has beenshown that ginsenoside, the effective component of ginseng, can enhance expression of choline acetyl transferase, as well as brain-derived neurotrophic factor （BDNF） and its receptor tyrosine kinase B （TrkB）, in cholinergic neurons of the basal forebrain. OBJECTIVE： To qualitatively and quantitatively verify the influence of ginsenoside on expression of BDNF and its receptor, TrkB, in the medial septum of aged rats, and to provide a molecular basis for clinical application. DESIGN~ TIME AND SETTING： A contrast study, which was performed in the Department of Anatomy, China Medical University, and the Department of Anatomy, Shenyang Medical College between December 2005 and May 2007. MATERIALS： Thirty-five, healthy, female, Sprague Dawley rats were selected for this study. Ginsenoside （81% purity） was provided by Jilin Ji＇an Wantai Chinese Medicine Factory; anti-BDNF antibody, anti-TrkB antibody, and their kits were provided by Wuhan Boster Company. METHODS： A total of 35 rats were divided into three groups： young （four months old）, aging （26 months old）, and ginsenoside. Rats in the ginsenoside group were administered ginsenoside （25 mg/kg/d） between 17 months and 26 months. MAIN OUTCOME MEASURES： Immunohistochemistry and in situ hybridization were used to measure expression of BDNF and TrkB in the medial septum of aged rats, and the detected results were expressed as gray values. RESULTS： （1） Qualitative detection： using microscopy, degenerative neurons were visible in the medial septum in the aging group. However, neuronal morphology in the ginsenoside group was similar to neurons in the young group. （2） Quantitative detection： the mean gray value of BDNF-positive and TrkB-positive products in the aging group were significantly higher than in the young group （t = 3.346, 4.169, P 〈 0.01）; however, the mean gray value in the ginsenoside group was significantly lower than in the aging group （t = 2.432, 2.651, P 〈 0.01）. CONCLUSION： Ginsenoside can increase expression of BDNF and TrkB in the medial septum and delay the natural degeneration in aged rats.
文摘Olfactory bulbectomy (OBX) causes cognitive dysfunction by degeneration of cholinergic neurons in the medial septum. Here, we define an involvement of nicotinic acetylcholine receptor (nAChR) in neuroprotective effect of donepezil in the septum neurons of OBX mice. Neuroprotective effects on the medial septal cholinergic neurons were assessed after chronic donepezil administration in OBX mice. We also measured Akt and ERK phosphorylation to define the neuroprotective mechanism of donepezil. We found that treatment with donepezil (1 - 3 mg/kg) for 15 consecutive days completely rescued cholinergic neurons in the OBX mice with concomitant improved memory. Reduction of both protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) phosphorylation were restored by chronic donepezil administration (1 - 3 mg/kg) in OBX mouse medial septum. Both phosphorylated Akt and ERK immunoreactivities were localized in cell bodies of choline acetyltransferase (ChAT)-positive cholinergic cells in the medial septum. Enhancement of Akt and ERK phosphorylation seen following donepezil administration was totally blocked by pre-administration of mecamylamine (10 μM), a nicotinic acetylcholine receptor antagonist. Donepezil increases phosphorylation of Akt and ERK via nAChR stimulation in the medial septum cholinergic neurons. The Akt and ERK stimulation by donepezil is associated with its ability of neuroprotection in the medial septum and memory improvement.
文摘目的探讨内侧隔斜角带复合体(medial septum-diagonal band of Broca complex,MS-DB)中5-HT1A受体在帕金森病(Parkinson's disease,PD)认知功能中的作用及机制。方法以6-羟基多巴胺(6-hydroxydopamine,6-OHDA)损毁单侧内侧前脑束(medial forebrain bundle,MFB)的PD模型大鼠为对象,采用行为学和电生理学方法,观察激活或阻断MS-DB中5-HT1A受体对PD认知功能和海马theta节律的影响。结果 (1)单侧MFB损毁降低了大鼠在T-迷宫实验中的选择正确率,MS-DB局部注射5-HT1A受体激动剂8-OH-DPAT进一步降低模型组大鼠在T-迷宫实验中的选择正确率,而MS-DB局部注射选择性5-HT1A受体拮抗剂WAY100635升高模型组大鼠的选择正确率;(2)单侧MFB损毁使海马theta节律的峰频率降低,MS-DB局部注射8-OH-DPAT抑制海马theta节律,降低theta节律的标准化功率,而MS-DB局部注射WAY100635诱发海马theta节律,并使theta节律的标准化功率升高。结论阻断MS-DB中的5-HT1A受体可改善模型组大鼠的工作记忆,这可能是通过兴奋海马theta节律来实现的。
