Impairment of long-term potentiation and spatial memory in leptin receptor-deficient rodents
Impairment of long-term potentiation and spatial memory in leptin receptor-deficient rodents
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DOI：
10.1016/s0306-4522(02)00162-8
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发表时间：
2002-01-01
期刊：
影响因子：
3.3
通讯作者：
Hori, T
中科院分区：
文献类型：
--
作者：
Li, XL;Aou, S;Hori, T
众所周知，瘦素通过其对下丘脑的作用参与控制摄食、生殖和神经内分泌功能。然而，瘦素受体存在于下丘脑以外的大脑区域（包括海马和大脑皮层），表明下丘脑外功能。我们研究了两种瘦素受体缺陷啮齿动物（Zucker大鼠和db/db小鼠）的海马长时程增强（LTP）和长时程抑制（LTD）以及空间记忆功能。在脑切片中，两种品系的海马CA 1区均显示LTP和LTD的损伤;瘦素（10（-12）M）对两种品系的这些损伤均无改善作用。这些菌株还表现出较低的基础水平的Ca 2 +/钙调蛋白依赖性蛋白激酶II活性在CA 1区比各自的控制，和水平没有响应强直刺激。这些品系在Morris水迷宫测试中也表现出受损的空间记忆（即，在训练期间较长的游泳路径长度和在探针测试中较不频繁地穿过平台的原始位置。从这些结果中，我们认为瘦素受体缺陷动物在CA 1中表现出受损的LTP和差的空间记忆，至少部分是由于海马中瘦素受体的缺陷。(C)2002年IBRO。由爱思唯尔科技有限公司出版。保留所有权利。
Leptin is well known to be involved in the control of feeding, reproduction and neuroendocrine functions through its action on the hypothalamus. However, leptin receptors are found in brain regions other than the hypothalamus (including the hippocampus and cerebral cortex) suggesting extrahypothalamic functions. We investigated hippocampal long-term potentiation (LTP) and long-term depression (LTD), and the spatial-memory function in two leptin receptor-deficient rodents (Zucker rats and db/db mice). In brain slices, the CA1 hippocampal region of both strains showed impairments of LTP and LTD; leptin (10(-12) M) did not improve these impairments in either strain. These strains also showed lower basal levels of Ca2+/calmodulin-dependent protein kinase II activity in the CA1 region than the respective controls, and the levels did not respond to tetanic stimulation. These strains also showed impaired spatial memory in the Morris water-maze test (i.e. longer swim-path lengths during training sessions and less frequent crossings of the platform's original location in the probe test.From these results we suggest that the leptin receptor-deficient animals show impaired LTP in CA1 and poor spatial memory due, at least in part, to a deficiency in leptin receptors in the hippocampus. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved.