| Co-Investigator(Kenkyū-buntansha) |
YASAKA Toshiharu Kyushu University, Dept.of Physiology, JSPS Research Fellow, 大学院・医学研究院, 学長・特別研究員
TAKE Sachiko Kyushu University, Dept.of Physiology, Assistant Professor, 大学院・医学研究院, 助手 (80253425)
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| Research Abstract |
It is well known that a variety of cytokines, growth factors and cell adhesion molecules are synthesised in the brain, and affect the neuronal activities, thereby playing a role in the mechanisms of homeostasis and stress responses. Receptor tyrosine kinase, c-kit, is expressed in mast cells and their precursor cells, and involved in the differentiation and proliferation of mast cells by the action of its ligand, stem cell factor (SCF). However, recent anatomical studies have shown that both c-kit and SCF are found in the hippocampus of the adult rat and mouse. In the present study, therefore, we investigated a role of c-kit/SCF signaling in learning and memory, and found the following results.
(1) The homozygous (Ws/Ws)mutant rats, that have deletion of 4 amino acids in the tyrosine kinase domain of c-kit receptors and a very low kinase activity, shown a deficit in spatial learning and memory in Morris water maze.
(2) The c-kit mutant rats also demonstrated an impariment of paired-pulse
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facilitation (PPF) and the tetanus-induced long-term potentiation (LTP) in the hippocampal mossy fiber (MF)-CA3 pathway but not in the Schaffer collateral/commissural (S/C)-CA1 pathway.
(3) When recombinant mouse SCF was applied to the hippocampal slices of normal mice, SCF acted on the postsynaptic c-kit receptors, then activated PI3'-kinase and phospholipased A2, As a result, PPF in the MF-CA3 pathway was affected as it was after the establishment of LTP.It is considered that arachidonic acid plays a role as a retrograde neurotransmitter in the action of SCF.
(4) In mouse slice preparations, the contents of SCF and c-kit mRNA were decreased after the tenic stimulation was applied to the MF-CA3 pathway. The quantitative measurement of mRNA levels were performed by a real-time capillary RT-PCR method.
(5) The amount of SCF and c-kit mRNA in the mouse brain decreased after 8 days isolation stress.
Thus it is concluded that c-kit/SCF signaling plays a significant role in the hippocampal synaptic potentiation and learning and memory in adult animals and that stressful stimuli affected the expression of SCF amd c-kit mRNA, which may result in the impairment of learing and memory during stress responses. Less
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