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A study on the facilitation of learning and memory elicited by food intake.

一项关于食物摄入促进学习和记忆的研究。

基本信息

批准号：
06454151
负责人：
SASAKI Kazuo
金额：
$ 4.61万
依托单位：
Toyama University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1996
项目状态：
已结题

项目摘要

(1) Intracerebroventricular (i.c.v.) infusion of some N-terminal fragments of acidic fibroblast growth factor (aFGF) such as aFGF (1-20) and aFGF (1-29) had no effect on food intake in rtas. However, infusion of [Ala^<16>] aFGF (1-29), in which a cysteine residue at position 16 was replaced by an alanine residue, significantly decreased food intake. In contrast, intrahypothalamic infusion of anti-FGF receptor-1 antibody increased food intake.(2) Intraperitoneal (i.p.) injection of glucose, which increases aFGF level in the cerebrospinal fluid, facilitates learning and memory in mice when tested by passive avoidance and Morris water maze tasks. This glucose effect was abolished by i.c.v.anti-aFGF antibody infusion 30 min before the i.p.glucose injection.(3) Effect of aFGF and aFGF(1-15) on neuronal activity in the parvocellular part of the paraventricular nucleus (PPPVN) in the hypothalamus was investigated in rat slice experiment. Both peptides increased the activity in more than half of PPPVN neurons. The result suggest that aFGF and aFGF (1-15) activate the hypothalamo-pituitary-adrenal axis, since PPPVN includes many CRF-containing neurons.(4) In senescence accelerated mouse (SAMP/8) which is known in deteriorating ability of learning and memory with age, subcutaneous injection of aFGF and [Ala^<16>] aFGF (1-29) was continued for 9 months at a frequency of once a week. In control SAMP/8, cell death and decrease of ChAT activity were observed in medial septum cholinergic neurons. These deficits were blocked in peptide-treated SAMP/8 and impairment of learning and memory seen in control SAMP/8 was ameliorated.

(1)脑室内(i.c.v.)输注酸性成纤维细胞生长因子N端片段，如aFGF(1-20)和aFGF(1-29)，对RTAS的摄食量没有影响。然而，注射[Ala^&lt；16&gt；]aFGF(1-29)，其中16位的半胱氨酸残基被丙氨酸残基取代，显著减少了食物的摄入量。相反，下丘脑内注射抗成纤维细胞生长因子受体-1抗体可增加摄食量。(2)腹膜内注射(I.P.)在被动回避和Morris水迷宫测试中，注射葡萄糖会增加脑脊液中aFGF的水平，从而促进小鼠的学习和记忆。(3)在大鼠脑片实验中，观察了aFGF1-15对下丘脑室旁核(PPPVN)小细胞部神经元活动的影响。这两种多肽都能增强一半以上的PPPVN神经元的活性。结果提示，由于PPPVN中含有大量的CRF能神经元，故其激活了下丘脑-垂体-肾上腺轴。(4)对学习记忆能力随增龄而下降的衰老加速小鼠(SAMP/8)，皮下注射aFGF和[Ala^&lt；16&gt；]aFGF(1-29)，每周1次，连续9个月。对照组SAMP/8中隔内侧胆碱能神经元细胞死亡，ChAT活性降低。多肽治疗的SAMP/8组这些缺陷被阻断，而对照组SAMP/8组的学习和记忆障碍得到改善。