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Synaptic Plasticity

開催日 2014/9/12
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

Allopregnanolone increases the density of drebrin clusters along dendrite

  • P2-049
  • 清水 英雄 / Hideo Shimizu:1 石塚 佑太 / Yuta Ishizuka:1 白尾 智明 / Tomoaki Shirao:1 
  • 1:群馬大学・院医・神経薬理 / Dept of Neurobiol & Behav, Gunma Univ Grad Sch of Med, Gunma, Japan 

Allopregnanolone (APα; 5α-pregnan-3α-ol-20-one) is a derivative of progesterone that is produced in both the periphery and the central nervous system (CNS) via enzymatic conversions of progesterone. APα has been shown to be stress sensitive in rat models, with CNS levels rising quickly following acute stress. It is known that various stresses, such as physical stress and psychological stress, cause neurological disorders including depression. Although the molecular mechanism of pathogenesis of these disorders is not yet clarified, the impairment of synapses is thought to be common pathological change of these disorders. APα is shown to positively modulate GABAA receptor-evoked responses. APα promotes neurogenesis in the hippocampal subgranular zone in mouse model of Alzheimer ’s disease. But the effect of APα on excitatory synapses is not clarified. In this study, we examined whether APα is involved in the dendritic spine function. We prepared primary hippocampal cultured neurons according to Banker ’s method, and treated them with APα at 13 and 20 days in vitro (DIV). At 24 hours after the treatment, the cells were fixed and immunostained with the antibody against drebrin, which is a postsynaptic actin cytoskeleton marker. Drebrin plays a pivotal role in the dendritic spine formation of neurons during development and is known to facilitate the accumulation of other postsynaptic proteins into dendritic spines. We defined the cluster of drebrin as a round staining region with a peak fluorescent level that was twofold greater than the averaged fluorescent level of the dendrites, and measured them along dendrites. At 20 DIV, 0.1 μM APα treatment for 24 hours had no effect on number of the clusters. On the other hand, both of 0.3 and 1 μM APα treatment for 24 hours significantly increased the density of drebrin clusters. Furthermore, At 13 DIV, 1 μM APα treatment increased the density of dendritic spines. These results suggest that APα modulates actin cytoskeleton on dendritic spines.

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