SAK3-Induced neuroprotection is mediated by nicotinic acetylcholine receptors

Koji Fukunaga, Yasushi Yabuki

研究成果: Chapter

3 被引用数 (Scopus)

抄録

Cholinergic neurotransmission plays a critical role in neuronal plasticity and cell survival in the central nervous system (CNS). Two types of acetylcholine receptors (AChRs), muscarinic AChRs (mAChRs) and nicotinic AChRs (nAChRs), trigger intracellular signaling through G protein activity and ion influx, respectively. To assess mechanisms underlying neuroprotection through nAChRs, we developed SAK3, a novel modulator of nAChR activity. Recently, we found that SAK3 enhances T-type calcium channel activity, promoting ACh release in the hippocampal CA1 region of olfactory-bulbectomized mice. Here, we observed potent SAK3 neuroprotective activity in mice with 20-min bilateral common carotid artery occlusion (BCCAO) or hypothyroidism. Treatment of mice with the α7 nAChR-selective inhibitor methyllycaconitine (0.5 mg/kg/day, p.o.) antagonized SAK3-mediated neuroprotection and memory improvement in BCCAO mice. Single administration of the anti-Graves' disease therapeutic methimazole (MMI) to female mice disrupted olfactory bulb (OB) glomerular structure, and cholinergic neurons largely disappeared in the medial septum followed by memory loss. Chronic SAK3 (0.5-1 mg/kg, p.o.) administration significantly rescued the number of cholinergic medial septum neurons in MMI-treated mice and improved cognitive deficits seen in those mice. Overall, our study suggests that, in mice, the novel nAChR modulator SAK3 can rescue neurons impaired by transient ischemia and hypothyroidism. We also address mechanisms common to SAK3-induced neuroprotection in both conditions.

本文言語English
ホスト出版物のタイトルNicotinic Acetylcholine Receptor Signaling in Neuroprotection
出版社Springer Singapore
ページ159-171
ページ数13
ISBN(電子版)9789811084881
ISBN(印刷版)9789811084874
DOI
出版ステータスPublished - 2018 4 4

ASJC Scopus subject areas

  • 医学(全般)
  • 神経科学(全般)
  • 薬理学、毒性学および薬学(全般)

フィンガープリント

「SAK3-Induced neuroprotection is mediated by nicotinic acetylcholine receptors」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル