Leptin facilitates learning and memory performance and enhances hippocampal CA1 long-term potentiation and CaMK II phosphorylation in rats
Leptin facilitates learning and memory performance and enhances hippocampal CA1 long-term potentiation and CaMK II phosphorylation in rats
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DOI：
10.1016/j.peptides.2006.07.001
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发表时间：
2006-11-01
期刊：
影响因子：
3
通讯作者：
Sasaki, K.
中科院分区：
文献类型：
--
作者：
Oomura, Y.;Hori, N.;Sasaki, K.
瘦素是一种由肥胖基因编码的脂肪细胞因子，在脂肪组织中表达，通过分布在大脑特别是下丘脑的瘦素受体影响摄食行为、产热和神经内分泌状态。瘦素还可能调节与学习和记忆相关的突触可塑性和行为表现，因为：瘦素受体存在于海马区，瘦素及其受体在结构和功能上与调节海马长时程增强(LTP)的白介素6细胞因子家族有相似之处。因此，我们研究了瘦素对(1)情绪和空间学习任务中的行为表现，(2)Schaffer侧支-CA1突触的LTP，(3)海马CA1神经元的突触前和突触后活动，(4)CA1神经元的细胞内钙浓度([Ca2+])，以及(5)表现LTP的海马CA1组织的钙/钙调蛋白激酶11(CaMK II)的活性的影响。静脉注射5和/或50微克/公斤的瘦素，但不注射500微克/公斤的瘦素，可促进被动回避和Morris水迷宫任务中的行为表现。脑片实验中应用10(-12)M瘦素可增强LTP，增加突触前递质的释放，而10(-10)M Leptin则抑制LTP，降低突触后受体对N-甲基-D-天冬氨酸的敏感性。10(-12)M瘦素引起的[Ca~(2+)]升高是10(-12)M瘦素引起的[Ca~(2+)]升高两倍。此外，瘦素对LTP的促进(10(-12)M)和抑制(10(-10)M)与CaMK II钙非依赖性活性的增减密切相关。我们的结果表明，瘦素不仅影响下丘脑的功能(如摄食、产热和神经内分泌状态)，还调节高级神经功能，如与学习和记忆相关的行为表现和海马突触可塑性。(C)2006年，由爱思唯尔公司出版。
Leptin, an adipocytokine encoded by an obesity gene and expressed in adipose tissue, affects feeding behavior, thermogenesis, and neuroendocrine status via leptin receptors distributed in the brain, especially in the hypothalamus. Leptin may also modulate the synaptic plasticity and behavioral performance related to learning and memory since: leptin receptors are found in the hippocampus, and both leptin and its receptor share structural and functional similarities with the interleukin-6 family of cytokines that modulate long-teen potentiation (LTP) in the hippocampus. We therefore examined the effect of leptin on (1) behavioral performance in emotional and spatial learning tasks, (2) LTP at Schaffer collateral-CA1 synapses; (3) presynaptic and postsynaptic activities in hippocampal CA1 neurons, (4) the intracellular Ca2+ concentration ([Ca2+];) in CA1 neurons, and (5) the activity of Ca2+/calmodulin protein kinase 11 (CaMK II) in the hippocampal CA1 tissue that exhibits LTP. Intravenous injection of 5 and/or 50 mu g/kg, but not of 500 mu g/kg leptin, facilitated behavioral performance in passive avoidance and Morris water-maze tasks. Bath application of 10(-12) M leptin in slice experiments enhanced LTP and increased the presynaptic transmitter release, whereas 10(-10) M leptin suppressed LTP and reduced the postsynaptic receptor sensitivity to N-methyl-D-aspartic acid. The increase in the [Ca2+], induced by 10(-12) M leptin was two times greater than that induced by 10(-12) M leptin. In addition, the facilitation (10(-12) M) and suppression (10(-10) M) of LTP by leptin was closely associated with an increase and decrease in Ca2+-independent activity of CaMK II. Our results show that leptin not only affects hypothalamic functions (such as feeding, thermogenesis, and neuroendocrine status), but also modulates higher nervous functions, such as the behavioral performance related to learning and memory and hippocampal synaptic plasticity. (c) 2006 Published by Elsevier Inc.