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大鼠基底前脑注射HC-3:迷宫学习缺陷与神经病理学

Basal forebrain infusion of HC-3 in rats: maze learning deficits and neuropathology.

作者信息

Hurlbut B J, Lubar J F, Switzer R, Dougherty J, Eisenstadt M L

出版信息

Physiol Behav. 1987;39(3):381-93. doi: 10.1016/0031-9384(87)90239-3.

DOI:10.1016/0031-9384(87)90239-3
PMID:3575480
Abstract

Ten adult male Sprague-Dawley rats were infused with hemicholinium (HC-3) using mini-osmotic pumps over a 14 day period through bilateral, chronically implanted cannulae in the nucleus basalis magnocellularis (nbm). Ten matched controls were infused in the same fashion with saline. HC-3 rats receiving implants demonstrated a significant deficit in maze-learning ability compared with individual and group performances before receiving the implants. In saline rats there was no significant difference in maze-learning ability before and after receiving implants. The HC-3 group receiving implants demonstrated a significant deficit in maze-learning ability compared with the saline control group. Serial sections through nbm from control and HC-3 rats indicated that all cannulae were located within infusion range of nbm. In HC-3 subjects, cholinergic cell bodies were destroyed with concurrent degeneration of terminal fields in cortex. Except for cannula insertion damage, the cholinergic neurotransmitter system appeared unharmed in controls. Stains for neuritic plaques and neurofibrillary damage were negative in both groups. The memory deficit in experimental subjects supported by the demonstrated destruction of nbm cholinergic neurons suggests that HC-3 may be useful in the development of an animal model for Alzheimer's Disease.

摘要

十只成年雄性斯普拉格-道利大鼠通过双侧长期植入基底大细胞核(nbm)的套管,使用微型渗透泵在14天内输注了半胆碱(HC-3)。十只匹配的对照大鼠以同样的方式输注生理盐水。与接受植入前的个体和群体表现相比,接受植入的HC-3大鼠在迷宫学习能力上表现出显著缺陷。在生理盐水组大鼠中,接受植入前后的迷宫学习能力没有显著差异。与生理盐水对照组相比,接受植入的HC-3组在迷宫学习能力上表现出显著缺陷。对对照大鼠和HC-3大鼠的nbm进行连续切片显示,所有套管都位于nbm的输注范围内。在HC-3组中,胆碱能细胞体被破坏,同时皮质终末场发生变性。除了套管插入造成的损伤外,对照组的胆碱能神经递质系统似乎未受损害。两组的神经炎性斑块和神经原纤维损伤染色均为阴性。nbm胆碱能神经元的破坏支持了实验对象的记忆缺陷,这表明HC-3可能有助于开发阿尔茨海默病的动物模型。

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Hemicholinium-3 impairs spatial learning and the deficit is reversed by cholinomimetics.半胱氨酸-3会损害空间学习能力,而拟胆碱药可逆转这种缺陷。
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