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Dematuration in the adult brain

開催日 2014/9/12
時間 15:00 - 17:00
会場 Room D(503)
Chairperson(s) 小林 克典 / Katsunori Kobayashi (日本医科大学大学院医学研究科薬理学分野 / Department of Pharmacology, Nippon Medical School, Japan)
宮川 剛 / Tsuyoshi Miyakawa (藤田保健衛生大学 総合医科学研究所 システム医科学研究部門 / Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Japan)

Activity-dependent reduction of expression of neuronal maturation markers in the adult hippocampal neurons

  • S2-D-1-4
  • 瀬木(西田) 恵里 / Eri Segi-Nishida:1 
  • 1:京都大学 / Center for Integrative Edu. Grad.Sch.of Pharm.Sci., Kyoto Univ., Kyoto, Japan 

Neuronal excitation has been demonstrated to promote adult neurogenesis including maturation of immature neurons of dentate gyrus (DG) in adult mice. We are exploring a distinct possibility that enhanced neuronal activity reverses the state of maturation in mature adult neurons. To examine the mechanisms to induce neuronal "dematuration", we examined the effect of electroconvulsive stimulation (ECS) that can activate excitatory glutamatergic signaling in the hippocampus on mature granule cells of adult DG. To evaluate the state of neuronal maturation, we focused on expression of markers of mature granule cells including calbindin (Calb1). A single as well as repeated ECS significantly reduced the expression of Calb1 in the DG. The reduction of Calb1 expression was transient after a single ECS, while repeated ECS continually down-regulated Calb1 expression, indicating that ECS rapidly initiates dematuration of granule cells, and repeated ECS treatments convert it into a long-lasting form. We then examined the signaling pathway involved in the rapid induction of granule cell dematuration by ECS. NMDA receptor antagonists and a protein synthesis inhibitor attenuated the reduction of maturation markers by a single ECS, suggesting that NMDA receptor activation and de novo protein synthesis are required for induction of neuronal activity-dependent dematuration in the DG. We also explored the mechanisms supporting long-lasting dematuration and found that pharmacological augmentation of GABAergic signaling by diazepam significantly reversed the reduction of maturation markers by repeated ECS. These findings suggest that neuronal excitation causes a robust reversal of the established state of maturation of granule cells by glutamatergic signaling at least in part. Together with the fact that neuronal excitation generally promotes the process of maturation in adult-born immature neurons, neuronal activity increases the proportion of younger neurons in the adult DG at both directions, i.e. increase of newborn neurons and dematuration of mature neurons.

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