硫化和多硫化诱导GABA/谷氨酸/D-血清的释放,促进海马的LTP,并调节行为过度活跃
Hiroki Furuie1, Yuka Kimura2, Tatsuhiro Akaishi3
1Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
硫化 (H2S) 和多硫化 (H2Sn) 是影响记忆和大脑功能的关键信号分子. 它们在神经递质释放中的作用以及对认知缺陷的潜在治疗应用现在更加清晰.
科学领域:
- 神经科学是一个神经科学.
- 生物化学 生化学
- 分子生物学分子生物学
背景情况:
- 硫化 (H2S) 和多硫化 (H2Sn) 是内生信号分子.
- 3-mercaptopyruvate硫转移酶 (3MST) 产生H2S/H2Sn,通过N-甲基-D-酸盐 (NMDA) 受体活性影响记忆形成等生理作用.
- 在神经递质释放,长期强化 (LTP) 调节和行为方面,H2S/H2Sn的前突触功能仍然在很大程度上未被阐明.
研究的目的:
- 研究H2S/H2Sn对神经递质释放和LTP诱导的前突触作用.
- 探索3MST和短暂受体潜在基林1 (TRPA1) 通道在H2S/H2Sn信号传输中的作用.
- 评估改变H2S/H2Sn信号的行为后果,特别是与NMDA受体对抗和精神疾病有关的行为后果.
主要方法:
- 在老鼠海马体内进行体内微透析以测量神经递质释放.
- 基因淘汰模型 (3MST和TRPA1) 研究这些分子的生理作用.
- 评估与NMDA受体功能相关的LTP诱导和行为测试.
主要成果:
- 应用H2S/H2S2诱导了海马体中GABA,谷氨酸和D-的释放.
- 3MST或TRPA1的遗传删除损害了LTP诱导,突出了它们的关键作用.
- 缺乏3MST导致对NMDA受体对抗剂的行为过敏,模仿精神分裂症类型的表型.
结论:
- H2S/H2Sn,3MST和TRPA1通道对于海马的LTP诱导和神经递质调节至关重要.
- 这种途径的失调与精神疾病相关的行为变化有关.
- 针对H2S/H2Sn-3MST-TRPA1轴为认知缺陷和精神疾病提供了潜在的治疗策略.
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