TY - JOUR
T1 - Leptin facilitates learning and memory performance and enhances hippocampal CA1 long-term potentiation and CaMK II phosphorylation in rats
AU - Oomura, Y.
AU - Hori, N.
AU - Shiraishi, T.
AU - Fukunaga, K.
AU - Takeda, H.
AU - Tsuji, M.
AU - Matsumiya, T.
AU - Ishibashi, M.
AU - Aou, S.
AU - Li, X. L.
AU - Kohno, D.
AU - Uramura, K.
AU - Sougawa, H.
AU - Yada, T.
AU - Wayner, M. J.
AU - Sasaki, K.
N1 - Funding Information:
This work was partly supported by the Japanese Ministry of Education, Culture, Sports, Science and Technology via Grants-in-Aid for Scientific Research (to NH, KS, TY, and TS), and by a Special Coordination Funds for Prompting Science and Technology (to KS). One of the authors (KS) would particularly like to thank Mr. Chikamitsu Nakayama for his encouragement throughout the present work.
PY - 2006/11
Y1 - 2006/11
N2 - 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-term 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+]i) in CA1 neurons, and (5) the activity of Ca2+/calmodulin protein kinase II (CaMK II) in the hippocampal CA1 tissue that exhibits LTP. Intravenous injection of 5 and/or 50 μg/kg, but not of 500 μg/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+]i induced by 10-10 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.
AB - 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-term 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+]i) in CA1 neurons, and (5) the activity of Ca2+/calmodulin protein kinase II (CaMK II) in the hippocampal CA1 tissue that exhibits LTP. Intravenous injection of 5 and/or 50 μg/kg, but not of 500 μg/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+]i induced by 10-10 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.
KW - CaMK II
KW - Hippocampus
KW - LTP
KW - Morris water maze
KW - Passive avoidance conditioning
KW - [Ca]
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UR - http://www.scopus.com/inward/citedby.url?scp=33750091967&partnerID=8YFLogxK
U2 - 10.1016/j.peptides.2006.07.001
DO - 10.1016/j.peptides.2006.07.001
M3 - Article
C2 - 16914228
AN - SCOPUS:33750091967
VL - 27
SP - 2738
EP - 2749
JO - Peptides
JF - Peptides
SN - 0196-9781
IS - 11
ER -
