NGF预防大鼠额叶皮质损伤后基底前脑胆碱能神经元变性

目的：为了观察神经生长因子（NGF）对大鼠额叶皮质损伤后基底前脑胆碱能神经元变性的预防效果。方法：24只SD大鼠,随机平均分为3组：（1）实验组（NGF）,（2）对照组（等容量的生理盐水）,（3）正常组（假手术）,用外科手术造成双侧额叶皮质局限性损伤,动物的学习,记忆机能及基底前脑含乙酰胆碱酯酶（AChE)活性神经元则分别用Y型迷宫和组织化学方法进行检测。结果：额叶皮质损伤4周后,动物的学习,记忆机能明显下降（P＜0．01）,基底前脑含AChE活性神经元明显减少（P＜0．01）,NGI治疗可有效地防止额叶皮质损伤大鼠学习,记忆障碍的发生及基底前脑含AChE活性神经元的减少（P＜0．05）。结论：NGF对双侧额叶皮质损伤大鼠的学习,记忆机能障碍及基底前脑胆碱能神经元变性有预防效果。     

神经干细胞移植对192-IgG-saporin阿尔茨海默病模型鼠基底前脑神经元p75NGFR阳性神经元和行为学的影响

神经干细胞能够在体外持续扩增,具有较强的增殖能力和较强的可塑性,能够在成年宿主中枢神经系统中存活、迁移、分化以及与宿主组织整合较好。 目的：分析神经干细胞移植对侧脑室注射192-IgG-saporin 老年性阿尔茨海默病模型鼠基底前脑神经元p75NGFR阳性神经元和行为学的影响。 方法：24只SD大鼠随机数字表法均分为3组：对照组、模型组、移植组。10只新生SD鼠(<24 h)用于神经干细胞分离培养。模型组及移植组192-IgG-saporin侧脑室注射SD大鼠建立阿尔茨海默病模型。造模后,移植组行基底前脑神经干细胞移植。4周后行Y迷宫检测,结合图像分析技术观察大鼠基底前脑p75NGFR阳性神经元数目和形态学参数的变化。 结果与结论：注射192-IgG-saporin 1个月,模型组损伤侧基底前脑内侧隔核和斜角带垂直支p75NGFR阳性神经元数明显减少(P < 0.01),移植组分别恢复到对照组的74.85%和71.66%,与模型组损伤侧相比较,差异显著(P < 0.01)。Y迷宫测试结果显示,移植组大鼠的空间学习能力和记忆能力有改善(P < 0.05),基底前脑p75NGFR阳性神经元细胞数与大鼠的空间学习记忆能力呈正相关。提示,神经干细胞移植对注射192-IgG-saporin致阿尔茨海默病鼠基底前脑胆碱能神经元有明显的补充和保护作用,可改善大鼠的学习记忆能力。     

IL—1β对大鼠胆碱能神经元的影响

目的探讨IL-1β对大鼠胆碱能神经元的损伤作用及机制。方法将IL-1β缓慢释放颗粒（IL-1βpellet）植入大鼠右侧Meynert核(nbM,基底核),复制胆碱能系统受损的动物模型;将不同剂量的人重组白细胞介素-1β（rhIL-1β）加入培养大鼠前脑基底神经元中,复制rhIL-1β诱导神经元损伤模型,检测（乙酰胆碱酯酶）AchE活性和脂质过氧化物（LPO）含量的变化。结果IL-1β损伤侧皮质AchE活性较未损伤侧、正常组及假手术组均显著降低（P<0.01）。50-500U/mlrhIL-1β可引起培养的神经元AchE活性明显下降（P<0.05）;100-500U/mlrhIL-1β可引起神经元LPO含量明显升高（P<0.01）。结论IL-1β慢性作用可以造成大鼠中枢胆碱能系统的损害,其机制可能是通过脂质过氧化作用。     

依达拉奉对沙鼠前额叶切除后学习与记忆的影响

目的 探讨依达拉奉对沙鼠前额叶切除后学习记忆的影响及其机制.方法 40只蒙古沙土鼠随机分为4组,假手术组、前额叶切除组、对照组、依达拉奉治疗组,每组10只.7 d后应用4-PTT (4-pellet taking test)旱路迷宫对各组沙鼠学习记忆功能进行评定.完成迷宫实验的沙鼠取脑组织行HE染色和胆碱能神经元免疫组化染色,观察海马 CA1 区神经元损伤程度,用锥体细胞密度评价,CHAT阳性胆碱能神经元细胞用真彩色图像分析系统定量和半定量分析.结果 4-PTT旱路迷宫实验显示,前额叶切除组中沙鼠参照记忆指标和工作记忆指标与假手术组有明显的差异(P＜0.05),依达拉奉治疗组上述指标显著改善(P＜0.05).假手术组未见坏死神经元,前额叶皮质切除组每个高倍视野中锥体细胞数和阳性胆碱能神经元数均少于假手术组,差异均有统计学意义(P＜0.05).依达拉奉治疗组每个高倍视野中锥体细胞数和阳性胆碱能神经元数均多于对照组,差异有统计学意义(P＜0.05).结论 依达拉奉能改善前额叶切除沙鼠的学习记忆能力,与其对胆碱能神经元的保护有关.     

大鼠脑损伤后NMDAR1表达及其认知障碍变化的关系

目的同步考量脑损伤后大鼠与认知功能较为密切的脑区N-甲基-D-天冬氨酸受体1（NMDAR1）表达与认知功能的变化。方法参照Feeney法建立大鼠创伤性脑损伤模型,伤后1d,2d,4d,7d1）．2免疫组化SABC法检测大鼠额叶皮质、海马区、基底前脑区NMDAR1表达,以行走实验、平衡实验及记忆功能测定评估大鼠认知障碍变化。结果轻、中型脑损伤组大鼠于伤后2d认知障碍最严重,分别于伤后3,7d基本恢复正常。轻型、中型脑损伤组脑额叶皮质、海马区、基底前脑区NMDAR1均于伤后1d升高,于2d降至较低水平后再呈缓慢增高趋势,与认知障碍变化趋势呈同步变化,且中型脑损伤组NMDAR1表达高于假手术组与轻型脑损伤组（P〈0．05）。结论大鼠经创伤性脑损伤后,额叶皮质、海马区、基底前脑区细胞中的NMDAR1含量和损伤后认知障碍的变化趋势有相似性;创伤性脑损伤后表达增加的NMDAR1对大鼠认知功能有加重损害作用。     

神经干细胞移植对老年痴呆模型鼠基底前脑小白蛋白阳性神经元和 学习记忆能力的影响*☆

目的：基底前脑是老年性痴呆患者脑皮质下神经元丢失最严重的区域，实验拟验证经神经干细胞移植治疗后老年痴呆鼠基底前脑小白蛋白阳性神经元的变化以及对其空间学习记忆能力方面的影响。 方法：实验于2005-12/2006-07在广州医学院解剖学教研室完成。①动物：清洁级SD雄性大鼠28只，随机数字表法分为3组：正常对照组8只、模型对照组8只、细胞移植组12只。另取10只新生SD鼠用于神经干细胞的分离培养。实验过程中对动物的处置符合动物伦理学标准。②实验方法：模型对照组、细胞移植组大鼠切断左侧穹隆海马伞，建立老年性痴呆动物模型。利用无血清培养技术获得鼠基底前脑神经干细胞，吸取2.5×1010 L－1细胞悬液4 μL，术后即刻细胞移植组损伤侧行细胞移植，坐标为前囟+0.6 mm，外侧+0.6 mm插入，腹侧-5.5 mm。③实验评估：移植后4周，采用Y型迷宫对各组动物进行学习记忆能力检测。麻醉后取脑制备组织切片，ABC法免疫组化染色结合图像分析观察各组大鼠基底前脑小白蛋白阳性神经元的变化。 结果：①对空间学习记忆能力的影响：细胞移植组空间学习能力、记忆能力均显著高于模型对照组（P < 0.05或P < 0.01），基本达到正常水平（P > 0.05）。②对小白蛋白阳性神经元的影响：与正常对照组比较，模型对照组损伤侧内侧隔核和斜角带核的小白蛋白阳性神经元数目分别减少62.5%和30.4%；细胞移植组降低幅度明显小于模型对照组（P < 0.01）。与正常对照组比较，模型对照组损伤侧内侧隔核、斜角带核小白蛋白阳性神经元的面积、周长、灰度均显著降低（P < 0.05或0.01）；细胞移植组上述指标较模型对照组均显著增加（P < 0.05或0.01）。③相关性分析：小白蛋白阳性神经元数目与大鼠在Y型迷宫中的学习次数呈显著负相关（r =-0.76~-0.79，P < 0.01），与记忆能力呈显著正相关（r = 0.78~0.84，P < 0.01）。 结论：神经干细胞移植对老年性痴呆模型鼠基底前脑退变的小白蛋白阳性神经元具有补充和保护作用，并能够明显改善其学习记忆能力，二者呈正性相关。     

卡因酸对大鼠学习记忆和P物质表达的影响

目的 :探讨卡因酸对大鼠学习记忆能力的影响 ,观察其基底前脑皮质 P物质表达的变化。方法 :大鼠腹腔注射卡因酸为实验组 ,注射磷酸缓冲生理盐水 (PBS)为对照组。用 Y迷宫测试大鼠学习记忆 ,用乙酰胆碱酯酶 (Ach E)化学染色检测神经元丢失情况 ,免疫组化检测 P物质表达水平的变化。结果 :实验组大鼠的学习记忆能力明显低于对照组 (P<0 .0 5 ) ,乙酰胆碱酯酶表达水平明显低于对照组 (P<0 .0 1) ,P物质表达水平明显高于对照组 (P<0 .0 1)。结论 :腹腔注射卡因酸可以损害大鼠的学习记忆能力 ,导致胆碱能神经元损害。过高浓度的 P物质可能参与卡因酸导致学习记忆受损的发病机制     

去卵巢大鼠胆碱能神经系统改变及雌激素保护作用机制的研究

目的观察去卵巢大鼠胆碱能神经系统的改变及雌激素对其影响。方法利用免疫组织化学染色结合图像分析方法观察去卵巢大鼠海马CA1区胆碱乙酰转移酶(ChAT)的变化;利用RT—PCR方法检测去卵巢大鼠基底前脑神经生长因子(NGF)mRNA表达的变化。结果去卵巢大鼠海马CA1区ChAT的积分光密度(OD)值降低,基底前脑NGFmRNA平均表达水平明显降低,补充雌激素后以上各项指标均明显提高。结论(1)去卵巢大鼠海马CA1区胆碱能神经元ChAT活性下降,基底前脑胆碱能神经元NGFmRNA表达水平降低。(2)雌激素能够上调去卵巢大鼠NGFmRNA表达．而NGF能够增强ChAT的活性。促进乙酰胆碱(Ach)的合成和释放,改善学习记忆能力。     

胚基底前脑和胚大脑皮质植入老年性痴呆模型鼠大脑皮质的研究

本文取15～17天胚龄的SD大鼠胚基底前脑和胚大脑皮质分别制成悬液植入老年性痴呆同种模型鼠的大脑额、顶叶皮质,存活10个月后进行主动和被动迷宫学习和记忆行为的测试以及组织学检查。结果表明移植入的胆碱能神经元在模型鼠脑中发挥功效,为脑移植治疗老年性痴呆提供一定的实验和理论依据。     

选择性5-HT1A受体拮抗剂WAY-100635抑制帕金森病模型大鼠腹内侧前额叶皮质的神经活动

目的 腹内侧前额叶皮质在随意运动的起始和控制、情感以及认知中具有重要作用.然而,黑质-纹状体通路变性后腹内侧前额叶皮质的神经活动和5-HT1A受体的作用仍不清楚.本研究观察了6-羟基多巴胺(6-hydroxydopamine,6-OHDA)损毁黑质致密部(substantia nigra pars compacta,SNc)后大鼠腹内侧前额叶皮质神经活动的变化和体循环给予选择性5-HT1A受体拮抗剂WAY-100635后神经元活动的改变.方法 采用在体玻璃微电极细胞外记录方法,记录正常大鼠和SNc单侧损毁大鼠的腹内侧前额叶皮质神经元的活动.结果 6-OHDA损毁SNc大鼠的腹内侧前额叶皮质神经元放电频率显著增加,放电形式没有明显改变.体循环给予WAY-100635(0.1 mg/kg,i.v.)不改变正常大鼠腹内侧前额叶皮质神经元的平均放电频率和放电形式,而显著降低了SNc损毁大鼠前额叶皮质神经元的平均放电频率.结论 黑质-纹状体通路的变性可导致腹内侧前额叶皮质神经活动增强,5-HT1A受体拮抗剂WAY-100635可以抑制这种活动增强,提示可能存在腹内侧前额叶皮质5-HT1A受体功能失调.     

Loss of NGF receptor immunoreactivity in basal forebrain neurons of aged rats: correlation with spatial memory impairment

Nerve growth factor (NGF) has recently been implicated as a trophic agent in the survival and maintenance of basal forebrain cholinergic neurons. To test the hypothesis that NGF may play a role in the age-related decline of cerebral cholinergic function and loss of cognitive ability, we investigated the possible correlation between the loss of basal forebrain neurons that stain for NGF receptor, and impairment of spatial reference memory performance in aged rats. Our results suggest that NGF receptor-positive basal forebrain neurons undergo marked cell atrophy and loss of neuropil staining in aged rats exhibiting impaired spatial learning and memory performance. Conversely, numerous, densely immunoreactive perikarya and a profuse neuritic plexus within the basal forebrain nuclei was consistently observed in behaviorally intact rats. Overall, the mean number of NGF receptor-positive basal forebrain neurons both in the nucleus of the diagonal band and nucleus basalis correlated with retention of the spatial task (r = 0.84 and r = 0.67, respectively; P less than 0.01). Our results support the view that progressive failure of retrograde trophic support due to the age-related loss of NGF receptors may promote degenerative changes in basal forebrain cholinergic neurons, and contribute to deterioration of cognitive ability in senescence.     

Cholinergic basal forebrain is critical for social transmission of food preferences

Studies using selective lesions of basal forebrain cholinergic neurons suggest that these neurons play a role in attentional processing, but not learning and memory. However, the tests of learning and memory used thus far have been restricted largely to spatial tasks. In the present study, we examined whether the cholinergic basal forebrain plays a role in a form of nonspatial associative memory, the social transmission of food preferences. Sham-operated control rats were compared to rats with 192 IgG-saporin lesions of the medial septum/diagonal band cholinergic projections to hippocampus or nucleus basalis magnocellularis/substantia innominata cholinergic projections to neocortex. Both lesions impaired 24-h retention of a learned social food preference relative to controls, despite performance on an immediate retention trial that was indistinguishable from controls. Moreover, 24-h retention of the socially learned food preference correlated strongly with cholinergic enzymatic activity in the neocortex, but not in the hippocampus. Immunohistochemical data confirmed significant and selective lesion-induced cholinergic depletions in the intended brain regions. These data provide evidence that the cholinergic basal forebrain, particularly the cholinergic projection to neocortex, is involved in the formation and/or retrieval of social memories related to food preference, and suggest a role for cortical acetylcholine in consolidation of associative memory processes.     

The cholinergic nuclei of the basal forebrain of the hamster (Mesocricetus auratus): a combined Golgi- and AChE-topochemical investigation

The cholinergic basal forebrain nuclear complex of the golden hamster was investigated Golgi-architectonically and AChE-topochemically using enzymehistochemical and immunohistochemical methods. We demonstrated 12 different classes of neurons in the whole basal forebrain complex with the Golgi-Kopsch-technique. The classical anatomical subdivision of the septal-region into nucleus medialis septi and nucleus tractus diagonalis has not been confirmed by results elaborated with this method. We found at least one class of neurons with varicose dendrites in every part of the cholinergic basal forebrain complex. The varicosities reacted positively for AChE. This morphological feature might be characteristic for cholinergic neurons in the nuclei of the basal forebrain complex.     

Loss of neurons in the rat basal forebrain cholinergic projection system after prolonged intake of ethanol

A reduction in the number of acetylcholinesterase (AChE)-positive neurons in the basal nucleus of Meynert complex (NbM, Ch 1 to Ch4) to 83% of control values was observed in rat after ethanol intake (20% v/v) for 12 weeks. Activity of choline acetyltransferase (ChAT) and AChE in the basal forebrain was simultaneously reduced to 74% and 81% and content of acetylcholine (ACh) to 56% of control values respectively. Neuronal loss showed a gradient over the rostro-caudal extension of the cholinergic projection system being most pronounced in the septal-diagonal band area and reaching 27% in the medial septum (Ch1). Number of AChE-positive neurons was insignificantly reduced in the pedunculopontine nucleus (Ch5) and unchanged in the laterodorsal tegmental gray of the periventricular area (Ch6). ACh content and activity of AChE was significantly reduced in target areas of the NbM such as cortex, hippocampus and amygdala, but changes were less pronounced than in the basal nucleus. The results indicate a neurotoxic effect of prolonged intake of ethanol on cholinergic neurons in the NbM leading to a partial cholinergic denervation of cortex, hippocampus and amygdala. Chronic intake of ethanol in rat is suggested to represent an animal model suitable to test the cholinergic hypothesis of geriatric memory dysfunction and to develop strategies for an amelioration of the impairment in memory and cognitive function in dementing disorders associated with a degeneration in the NbM such as postalcoholic dementia and Alzheimer's disease.     

Neurofibrillary degeneration of cholinergic and noncholinergic neurons of the basal forebrain in Alzheimer's disease

Two principal features of Alzheimer's disease (AD) are (1) the occurrence of neurofibrillary tangles (NFTs) and senile plaques, and (2) the loss of cortical cholinergic activity because of dysfunction of neurons in the basal forebrain cholinergic system. The relationship of these two abnormalities is an unresolved issue in the pathology of AD. We used polyclonal antibodies specific for paired helical filaments (PHFs), combined with acetylcholinesterase (AChE) histochemistry, to assess the cytoskeletal changes of cholinergic and noncholinergic neurons in the basal forebrain in AD. In both sporadic and familial AD, the nucleus basalis of Meynert (nbM) showed a marked decrease in AChE-positive (AChE+) perikarya and abundant immunoreactive NFTs. In double-labeling studies of the nbM, PHF reactivity was found both in surviving AChE+ neurons and in many AChE- NFTs that were not associated with microscopically recognizable cell structures. Some surviving AChE+ perikarya did not contain NFTs. Numerous NFTs and senile plaques were identified by PHF immunoreactivity in other basal forebrain areas, including subnuclei of the amygdala that showed low or absent AChE activity. We conclude that the dysfunction and death of cholinergic neurons in the nbM is associated with extensive NFT formation, including apparently residual NFTs in loci where nbM neurons once existed; and many noncholinergic neurons and neurites in the basal forebrain show NFT and senile plaque formation. The cytopathology of AD involves neurons of varying transmitter specificities, including cholinergic neurons in the basal forebrain.     

Developmental change in the nerve growth factor action from induction of choline acetyltransferase to promotion of cell survival in cultured basal forebrain cholinergic neurons from postnatal rats

Nerve growth factor (NGF), a well-characterized target-derived growth factor, has been postulated to promote neuronal differentiation and survival of the basal forebrain cholinergic neurons. In the present paper, we demonstrate that a developmental change in NGF action occurs in postnatal rat basal forebrain cholinergic neurons in culture. Firstly, NGF acts as maturation factor by increasing choline acetyltransferase (ChAT) activity and acts later as a survival factor. In dissociated cell cultures of septal neurons from early postnatal (P1-4) rats, ChAT activities were increased by the addition of NGF. That is, ChAT activities in P1 septal cells cultured for 7 days was increased 4-fold in the presence of NGF at a concentration of 100 ng/ml. However, the number of the acetylcholinesterase (AChE)-positive neurons was not significantly different between these groups. In contrast, septal neurons from P8 to P14 rats showed different responses to NGF. Although the P14 septal neurons in culture for 7 days without NGF lost about half of the ChAT activity during a 7-day cultivation, cells cultured with NGF retained the activity at the initial level. The number of AChE-positive neurons counted in cultures with NGF was much greater than the number without NGF. These results suggest that, during the early postnatal days, the action of NGF on the septal cholinergic neurons in culture changes from induction of ChAT activity to the promotion of cholinergic neuronal cell survival. During this developmental period in vivo, septal neurons are terminating their projections to the hippocampal formation. Similar NGF-regulated changes in cholinergic neurons were observed in cultured postnatal neurons from vertical limb of diagonal band. An analogy has been pointed out between the neuronal death of the basal forebrain cholinergic neurons and a similar neuronal death in senile dementia, especially Alzheimer's type. The work reported here might present a possibility that NGF could play a role in preventing the loss of the basal forebrain cholinergic neurons in this disease.     

Neurochemical and behavioral recovery after colchicine lesions of the nucleus basalis magnocellularis in rats

Experimentally-induced lesions of the basal forebrain have been used to test the hypothesis that the cholinergic system plays a critical role in learning and memory. In the present study, a basal forebrain infusion of colchicine, a microtubule assembly inhibitor, was used to characterize the relationship between a cholinergic marker and behavioral function. Bilateral infusions were made in the nucleus basalis magnocellularis (NBM) of male Long-Evans rats. At 4 weeks post-lesion, behavioral assessments were made on half of the rats in each group. These rats were sacrificed 1 week later and regional choline acetyltransferase (ChAT) activity was measured. The remaining rats were behaviorally tested 11 weeks post-lesion and sacrificed 12 weeks post-lesion. The brains of additional rats were studied for Nissl-staining, ChAT-, GAD- and metEnk immunoreactivity (IR) and AChE histochemistry. At 5 weeks after colchicine infusion, there was a significant decrease in parietal and frontal cortical ChAT activity, impaired acquisition of a water maze spatial navigation task and decreased passive avoidance cross-over latency. At 12 weeks after colchicine infusion, ChAT activity was decreased in frontal but not parietal cortex; acquisition of the water maze task was not significantly different from vehicle-infused rats, and a significant deficit was observed in passive avoidance latency. ChAT-IR in the NBM showed a significant decrease at both time points, while changes in AChE-stained cortical fibers paralleled the ChAT activity. GAD- and metEnk-IR were decreased but were not different between the two time points. These data show task-specific behavioral recovery associated in time with recovery of regional cholinergic markers.     

Cholinergic innervation of the song control nuclei by the ventral paleostriatum in the zebra finch: a double-labeling study with retrograde fluorescent tracers and choline acetyltransferase immunohistochemistry

During the sensitive period of song learning, the content of acetylcholine and the enzyme activity of choline acetyltransferase (ChAT) increase remarkably in the song control nuclei of a young male zebra finch. Cholinergic fibers innervate the two main song control nuclei of the forebrain: the higher vocal center (HVC) and the robust nucleus of the archistriatum (RA). The present study combines the retrograde tracer, Fluoro-Red (FRe), with ChAT immunohistochemistry. The results indicate that the cholinergic fibers which innervate the RA and HVC originate from the ventral paleostriatum (VP) in the basal forebrain, and that there is an anterior-posterior topography in the location of the cholinergic neurons in the VP that project to the HVC and RA, although there are a few neurons which project to both nuclei. These findings suggest that the VP is homologous to the nucleus basalis of Meynert of the basal forebrain cholinergic system of mammals which is associated with learning and memory processes, and that the cholinergic neurons in the VP play an important role in avian song learning.     

Lesions of the basal forebrain impair reversal learning but not shifting of attentional set in rats

The cholinergic neurons of the basal forebrain, which project to cortex, the thalamic reticular nucleus and the amygdala, are implicated in many aspects of attentional function, while the intrinsic neurons of the basal forebrain are implicated in learning and memory. This study compared the effects of lesions of the basal forebrain made with either the immunotoxin 192-IgG-saporin (which selectively destroys cholinergic neurons), or the non-selective excitotoxin, ibotenic acid (which destroys both cholinergic and non-cholinergic neurons) on a task which measure the acquisition and shifting of attentional set as well as the ability to learn reversals of specific stimulus-reward pairings. Rats learned to obtain food reward by digging in small bowls containing distinctive digging media that were differentially scented with distinct odours. They performed a series of two-choice discriminations, with the bait associated with either the odour or the digging medium. Rats with 192-IgG-saporin lesions of the basal forebrain were not impaired relative to control rats at any stage of the task. Rats with ibotenic acid lesions of the basal forebrain were impaired the first time stimulus-reward contingencies were reversed. They were not impaired in acquisition of new discriminations, even when an attentional-shift was required. These data are consistent with data from marmosets and so highlight the functional similarity of monkey and rodent basal forebrain. They also confirm the likely involvement of non-cholinergic neurons of the basal forebrain in reversal learning.     

Experimental immune-mediated damage of septal cholinergic neurons

Degeneration of cholinergic neurons in the medial septum and the diagonal band of Broca is a frequent neuropathological feature of Alzheimer's disease. To determine whether an immune process can injure these basal forebrain cholinergic neurons, we serially immunized guinea pigs with septal cholinergic hybrid cells (SN-56). Following immunization, a relatively selective damage of septal cholinergic neurons, reduction in septal choline acetyltransferase (ChAT) activity and decrease in acetylcholine release in hippocampus were detected. Serum IgG from guinea pigs immunized with SN-56 cells and stereotactically injected into the medial septal region of rats produced a loss of ChAT activity in the medial septum, frontal cortex and hippocampus, together with impairment of learning and long term spatial memory. These data suggest that relatively selective damage to septal cholinergic neurons can be caused by an immune-mediated process in experimental animals.