胆碱能系损伤老化鼠的脑神经肽表达与学习能力改变

The change of brain neuropeptide expression and learning ability for aged rat with damaged brain cholinergic neuron system

目的 探讨兴奋性神经毒素定位损伤脑胆碱能神经元的老化大鼠行为及脑组化改变 ,及在 AD发病中兴奋性毒素脑损伤的机制。方法 分别用兴奋性毒素鹅膏蕈氨酸 (IBA)、N-甲基 - D-天冬氨酸 (NMDA)定位损伤老化大鼠脑右侧 Meynert核。用 Y型迷宫法和分光光度法检测损伤大鼠学习能力和脑胆碱酯酶 (Ach E)活性改变 ,并用免疫组化染色法测定损伤动物脑神经肽 :β-淀粉样肽前体 (β- APP)、生长抑素 (SOM)及 P物质(SP)的表达。结果 脑损伤大鼠与对照组比较 ,表现学习能力及脑胆碱酯酶活性显著降低 (均 P<0 .0 5) ;鼠脑额叶皮层和海马区显示β- APP的表达明显升高 ;而生长抑素阳性神经元数量则显著减少。用 IBA及 β- AP2 5- 3 5同时或 NMDA损伤鼠脑时 ,可显示脑皮质区 P物质过表达 (均 P<0 .0 1 ) ;用IBA单独注射时 ,SP表达无显著改变。结论 以 IBA、NMDA定位损伤老化大鼠脑 Meynert核后 ,显示鼠脑胆碱能系统损伤 ,学习能力障碍 ,β- APP、P物质表达明显增多 ,可能与脑中 β- AP的沉积有关。神经肽 SOM表达降低可能致动物学习能力下降。该 AD模型动物表现 AD类似临床和病理特征。

Objective To determine the change of behaviour and brain histochemistry of the aged rats with site-specificly destruction of the brain cholinergic neurons system by excitatory neurotoxin. And to study the brain damage mechanism by excitatory neurotoxin in Alzheimer's disease. Methods To destroy the right nucleus of Meynert of old rats' brain site-specificly with excitatory neurotoxin ibotenic acid (IBA) and N-methyl-D-asparate(NMDA), then for the damaged rats the learning ability and brain acetylcholinesterase (AchE) activity was measured by Y-maze and spectrophotography method, and the expression of brain neuropeptide: β-amyloid peptide precursor (β-APP), somatostatin (SOM) and substance P (SP) were determined using immunohistochemistry method.Results Compared with the control group, the old rats undergoing brain damage show that their learning ability and the brain acetylcholinesterase activity is lower notably (all are P<0.05), in their brain frontal cortex and hippocampus the β-APP expression is higher but SOM positive neurons is less, and the SP expression is higher only in IBA andβ-AP 25-35 co-damaged and NMDA damaged groups , but not in IBA damaged , than that in control group significantly (all are P<0.01). Conclusions The old rats injured the brain Meynert nucleus with IBA and NMDA site-specificly display the damage of the brain cholinergic system and the learning desfunction. In addition they showed that β-APP is overexpressed and SP expression is higher significantly, that may be related to β-AP deposition in brain, the neuropeptide SOM expression is lower may cause to reduce their learning ability. The aforesaid characteristics of this AD animal model are similar to some AD patients' clinical and pathologic features.