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DHHC2调节恐惧记忆的形成,LTP和AKAP150在海马体中的信号传递
Meng-Die Li1, Lu Wang2, Yu-Qi Zheng1
1Department of Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou 350122, China.
iScience
|September 4, 2023
概括
棕酸转移酶 (PAT),特别是DHHC2,对于海马中的恐惧记忆和长期潜能 (LTP) 是至关重要的. DHHC2通过控制AKAP150的棕化来调节记忆,从而影响突触可塑性.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 生物化学 生化学
背景情况:
- 棕酸转移酶 (PAT) 参与学习和记忆,但它们的确切作用和机制尚不清楚.
- 了解记忆形成的分子基础对于解决认知障碍至关重要.
研究的目的:
- 研究DHHC2,一种特定的PAT在恐惧记忆和突触可塑性中的作用.
- 阐明DHHC2影响学习和记忆过程的分子机制.
主要方法:
- 恐惧调节在动物中,以评估记忆形成.
- 河马切片电生理学测量长期潜能 (LTP).
- 生物化学试验分析蛋白质棕化,化和相互作用 (例如AKAP150,PSD-95,GluA1).
- 基因操纵 (DHHC2淘汰) 和药物抑制 (2-甲酸).
主要成果:
- 在恐惧调节和突触刺激 (HFS,甘氨酸) 后,DHHC2活性和突触表达增加.
- DHHC2的淘汰损害了恐惧记忆和LTP,并在Ser845.5下降了GluA1酸化.
- 恐惧学习有选择地增加了AKAP150的手掌化,这种影响取决于DHHC2.2.
- 棕化抑制降低了AKAP150的棕化及其与PSD-95.5的相互作用.
结论:
- DHHC2是恐惧记忆和海马体LTP的关键调节者.
- DHHC2通过AKAP150的棕化介导其作用,影响突触可塑性和记忆巩固.
- 这些发现凸显了DHHC2作为与记忆相关疾病的潜在治疗点.
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