老年学习记忆减退大鼠的海马GABA能神经元数量变化
作者：柯尊记 姚志彬
单位：中山医科大学解剖学教研室、脑研究室，广州510089
关键词：老年性学习记忆减退；GABA能神经元；海马结构；Morris水迷宫；大鼠
解剖科学进展000215摘 要：为探讨γ-氨基丁酸(GABA)能神经元在老年脑的改变及其与老年性学习记忆减退间的关系。本研究通过Morris水迷宫测试将老年大鼠分为学习记忆正常和损害组，用免疫细胞化学和体现视学方法定量描述GABA能神经元的改变。结果显示，老年记忆正常和损害组海马本部各区的GABA能神经元均较年轻组明显减少，但正常组和损害组海马之间无显著性差异。齿状回分子层的GABA阳性神经元的数量仅在老年学习记忆损害组明显减少，且GABA神经元数量与搜寻平台的游泳时间呈负相关(r＝-0.91，P<0.01)。提示老年学习记忆能力减退可能与齿状回分子层的GABA能神经元丢失有关。
, http://www.100md.com
Change of GABAergic Neurons in Hippocampus of Aged Learning and Memory Impaired Rats
Ke Zunji ,Yao Zhibin
(Department of Anatomy and Brain Research, Sun Yat-sen University of Medical Sciences, Guangzhou 510089)
Abstract：The propose of this study was to explore the behavioral features and its relation to GABAergic neurons in the hippocampal formation of the aged rat. 40 aged SD rats (24 months) were divided into agedimpaired group and aged-unimpaired group according to the swim time of platform trial performance in the Morris water maze. 15 young rats (3 months) were used as control. The changes of GABAergic neurons in the hippocampus of the rats were estimated by immunocytochemical and stereological methos. The results showed that the average area densities (NA) of GABAergie neurons in subiculum, field CA1, field CAS, and field CA4 decreased in aged rats compared to the young rats , but no significant differences in the two aged groups. In the dentate gyrus, decrease of GABAergic neurons occurred only in aged impaired rats. Correlative analysis showed that the Na of GABAergic neurons in the molecular layer of dentate gyrus had a negative correlation with the mean escape latency in place discrimination learning (γ=-0. 91, P<0. 01). The results suggest that the loss of GABAergic neurons in the molecular layer of dentste gyrus is an important cause for the decline of learning and memory in the aged rat.
, 百拇医药
Keywords：memory impairment; GABAergic neurons; hippocampu; aged rats
基金项目：国家自然科学基金，广东省科学基金资助项目
参考文献：
[1]Sarter M, Bruno JP. Cognitive functions of cortical Ach: lessins from studies on transsynaptic modulation of activated efflux. TINS, 1994, 17(6): 217
[2]Sarter M, Schneider HH, Stephens DN. Treatment strategies for senile dementia; antagonist β-carbolines. TINS, 1988, 11:13
, 百拇医药
[3]Freund TF, Antal M, GABA-containing neurons in the septum control inhibitiry interneurons in the hippccampus. Nature,1988, 336:170
[4]Abdulla FA, Abu-Bakra MAJ, Calaminici MR, et al. Importance of forebrain cholingergic and GABAergic system to the age-related deficits in eater maze performance of rats. Neurobiol Aging, 1995, 16:41
[5]Griffith WH, Murchison DA. enhancement of GABA-activated membrane currents in aged Fisher-344 rat basal forebrain neurons. J Neurosci, 1995, 15:2407
, 百拇医药
[6]Nagahara AH, Brioni JD, McGaugh JL. Effects of intraseptal infusion of mascimol on inhibitory avoidance and spatial learning: differential effects of pretraining and posttraining administration.Psychobiology, 1992, 20:198
[7]Chavez ME, Salado CR, Sanchez AM, et al. Post-training injection of GABAergic antagonists into the striatum produces retrograde amnesia. Neurobiol Learning Memory, 1995, 63:296
[8]Hannila T, Sirvio J, Riekkinen PJ. The effects of γ-vinyl-GABA on the performance of nucleus basalis-lesinoed rats in spatial navigation task. Brain Res, 1990, 537:363
, http://www.100md.com
[9]Marczynski TJ, Artwohl J, Maczynska B. Chronic administration of flumazenil increses life-spen and protects rats from agerelated loss of cognitive function; a benzodiazepine/GABA hypothesis of brain aging. Neurobiol Aging, 1994, 15:69
[10]Gage FH, Bjorklund A. Cholinergic spetal grafts into the hippocampal formation improve spatial learning and memory in aged rats by an atropinesensitive mechanism. J Neurosci, 1986, 6:2837
, http://www.100md.com [11]Aika Y, Ren Jq, Kosaka K, et al. Quantitative analysis of GABA-Like immunoreactive and parvalbumin-containing neurons in the CA1 region of the rat hippocampus using a stereological method, the disector. Exp Brain Res, 1994, 99:267
[12]Krzywkowski P, De Bilbao F, Senut MC, et al. Age-related change in parvalbumin-and GABA-immunoreactive cells in the rat septum. Neurobiol Aging, 1995, 16:29
[13]Duter P, Potier B, Lamour Y, et al. Loss of calbindin-28K immunoreactivity in hippocampal slices from aged rats: a role for calcium? Eur J Neurosci, 1991, 3:839
, 百拇医药
[14]Sloviter RS. Decreased hippocampal inhibition and a selective loss of interneurons in experimental epilepsy. Science, 1987,235:73
[15]Marty S, Berninger B, Carroll P, et al. GABAergic stimulation regulates the phenotype of hippocampal interneurons througy the regulation of brainderived neuotrophic factors. Neuron 1996, 16:565, 百拇医药
单位：中山医科大学解剖学教研室、脑研究室，广州510089
关键词：老年性学习记忆减退；GABA能神经元；海马结构；Morris水迷宫；大鼠
解剖科学进展000215摘 要：为探讨γ-氨基丁酸(GABA)能神经元在老年脑的改变及其与老年性学习记忆减退间的关系。本研究通过Morris水迷宫测试将老年大鼠分为学习记忆正常和损害组，用免疫细胞化学和体现视学方法定量描述GABA能神经元的改变。结果显示，老年记忆正常和损害组海马本部各区的GABA能神经元均较年轻组明显减少，但正常组和损害组海马之间无显著性差异。齿状回分子层的GABA阳性神经元的数量仅在老年学习记忆损害组明显减少，且GABA神经元数量与搜寻平台的游泳时间呈负相关(r＝-0.91，P<0.01)。提示老年学习记忆能力减退可能与齿状回分子层的GABA能神经元丢失有关。
, http://www.100md.com
Change of GABAergic Neurons in Hippocampus of Aged Learning and Memory Impaired Rats
Ke Zunji ,Yao Zhibin
(Department of Anatomy and Brain Research, Sun Yat-sen University of Medical Sciences, Guangzhou 510089)
Abstract：The propose of this study was to explore the behavioral features and its relation to GABAergic neurons in the hippocampal formation of the aged rat. 40 aged SD rats (24 months) were divided into agedimpaired group and aged-unimpaired group according to the swim time of platform trial performance in the Morris water maze. 15 young rats (3 months) were used as control. The changes of GABAergic neurons in the hippocampus of the rats were estimated by immunocytochemical and stereological methos. The results showed that the average area densities (NA) of GABAergie neurons in subiculum, field CA1, field CAS, and field CA4 decreased in aged rats compared to the young rats , but no significant differences in the two aged groups. In the dentate gyrus, decrease of GABAergic neurons occurred only in aged impaired rats. Correlative analysis showed that the Na of GABAergic neurons in the molecular layer of dentate gyrus had a negative correlation with the mean escape latency in place discrimination learning (γ=-0. 91, P<0. 01). The results suggest that the loss of GABAergic neurons in the molecular layer of dentste gyrus is an important cause for the decline of learning and memory in the aged rat.
, 百拇医药
Keywords：memory impairment; GABAergic neurons; hippocampu; aged rats
基金项目：国家自然科学基金，广东省科学基金资助项目
参考文献：
[1]Sarter M, Bruno JP. Cognitive functions of cortical Ach: lessins from studies on transsynaptic modulation of activated efflux. TINS, 1994, 17(6): 217
[2]Sarter M, Schneider HH, Stephens DN. Treatment strategies for senile dementia; antagonist β-carbolines. TINS, 1988, 11:13
, 百拇医药
[3]Freund TF, Antal M, GABA-containing neurons in the septum control inhibitiry interneurons in the hippccampus. Nature,1988, 336:170
[4]Abdulla FA, Abu-Bakra MAJ, Calaminici MR, et al. Importance of forebrain cholingergic and GABAergic system to the age-related deficits in eater maze performance of rats. Neurobiol Aging, 1995, 16:41
[5]Griffith WH, Murchison DA. enhancement of GABA-activated membrane currents in aged Fisher-344 rat basal forebrain neurons. J Neurosci, 1995, 15:2407
, 百拇医药
[6]Nagahara AH, Brioni JD, McGaugh JL. Effects of intraseptal infusion of mascimol on inhibitory avoidance and spatial learning: differential effects of pretraining and posttraining administration.Psychobiology, 1992, 20:198
[7]Chavez ME, Salado CR, Sanchez AM, et al. Post-training injection of GABAergic antagonists into the striatum produces retrograde amnesia. Neurobiol Learning Memory, 1995, 63:296
[8]Hannila T, Sirvio J, Riekkinen PJ. The effects of γ-vinyl-GABA on the performance of nucleus basalis-lesinoed rats in spatial navigation task. Brain Res, 1990, 537:363
, http://www.100md.com
[9]Marczynski TJ, Artwohl J, Maczynska B. Chronic administration of flumazenil increses life-spen and protects rats from agerelated loss of cognitive function; a benzodiazepine/GABA hypothesis of brain aging. Neurobiol Aging, 1994, 15:69
[10]Gage FH, Bjorklund A. Cholinergic spetal grafts into the hippocampal formation improve spatial learning and memory in aged rats by an atropinesensitive mechanism. J Neurosci, 1986, 6:2837
, http://www.100md.com [11]Aika Y, Ren Jq, Kosaka K, et al. Quantitative analysis of GABA-Like immunoreactive and parvalbumin-containing neurons in the CA1 region of the rat hippocampus using a stereological method, the disector. Exp Brain Res, 1994, 99:267
[12]Krzywkowski P, De Bilbao F, Senut MC, et al. Age-related change in parvalbumin-and GABA-immunoreactive cells in the rat septum. Neurobiol Aging, 1995, 16:29
[13]Duter P, Potier B, Lamour Y, et al. Loss of calbindin-28K immunoreactivity in hippocampal slices from aged rats: a role for calcium? Eur J Neurosci, 1991, 3:839
, 百拇医药
[14]Sloviter RS. Decreased hippocampal inhibition and a selective loss of interneurons in experimental epilepsy. Science, 1987,235:73
[15]Marty S, Berninger B, Carroll P, et al. GABAergic stimulation regulates the phenotype of hippocampal interneurons througy the regulation of brainderived neuotrophic factors. Neuron 1996, 16:565, 百拇医药