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[单侧基底前脑损伤大鼠抗痴呆疗法的研究——盐酸比呋美林给药或迷走神经结状神经节自体移植后胆碱能标志物活性及事件相关电位的系列变化]

[Study on the anti-dementia therapies for rats with a unilateral basal forebrain lesion--serial changes of the cholinergic markers' activities and event-related potentials after the administration of bifemelane hydrochloride or autotransplantation of the vagal nodosal ganglion].

作者信息

Ikeda K, Yamashita J, Egashira T, Takayama F, Yamanaka Y

机构信息

Department of Neurosurgery, Kanazawa University School of Medicine, Japan.

出版信息

No To Shinkei. 1995 May;47(5):455-63.

PMID:7786622
Abstract

Using rats with a unilateral lesion in the nucleus basalis magnocellularis (NBM), we examined electrophysiologically the therapeutic effects of bifemelane (BIF) and autotransplantation of the vagal nodosal ganglion (X) on the event-related potential (P300) serially for 4 weeks, and also neurochemically their effects on cholinergic markers--the specific binding of 3H-QNB (quinuclidinyl benzilate) on muscarinic acetyl-choline receptor (mAChR) and the activities of acetylcholinesterase (AChE) and choline acetyltransferase (CAT). The latency of P300 was continuously delayed and its amplitude remained low voltage until 4 weeks in the NBM-lesioned rats (No-Tx group). Whereas the latency and amplitude returned to normal after 2-3 weeks in the rats given daily intraperitoneal injection of 15 mg/kg BIF (BIF group) and autotransplanted ones (X group). The cortical CAT and AChE levels on the lesion side did not recover until 4 weeks in No-Tx group, but the CAT levels recovered after 3 weeks in both BIF and X group; the AChE levels, after 1 week in BIF group and after 3 weeks in X group. The cortical mAChR on the lesion side was within or more than normal range in all rats. These results might indicate as follows: 1) Compensatory postsynaptic process such as cortical mAChR increase and AChE decrease occurred after acute cholinergic depletion. 2) Administration of BIF and X autotransplantation recovered cortical CAT and AChE levels and normalized cholinergic neuronal activity of P300.

摘要

我们使用在基底大细胞核(NBM)有单侧损伤的大鼠,连续4周通过电生理学方法检测了比呋内酰胺(BIF)和迷走神经结节状神经节自体移植(X)对事件相关电位(P300)的治疗效果,还通过神经化学方法检测了它们对胆碱能标志物——3H-QNB(甲基东莨菪碱)与毒蕈碱型乙酰胆碱受体(mAChR)的特异性结合以及乙酰胆碱酯酶(AChE)和胆碱乙酰转移酶(CAT)活性的影响。在NBM损伤的大鼠(未治疗组)中,P300的潜伏期持续延迟,其波幅在4周内一直保持低电压。而在每天腹腔注射15mg/kg BIF的大鼠(BIF组)和自体移植的大鼠(X组)中,潜伏期和波幅在2 - 3周后恢复正常。在未治疗组中,损伤侧皮质的CAT和AChE水平直到4周时才恢复,但在BIF组和X组中,CAT水平在3周后恢复;AChE水平在BIF组1周后恢复,在X组3周后恢复。所有大鼠损伤侧皮质的mAChR均在正常范围内或高于正常范围。这些结果可能表明:1)急性胆碱能耗竭后发生了诸如皮质mAChR增加和AChE减少等代偿性突触后过程。2)给予BIF和进行X自体移植可恢复皮质CAT和AChE水平,并使P300的胆碱能神经元活动恢复正常。

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