HSPA12A控制大脑乳酸平衡,以维持海马神经发生和情绪稳定
Jialing Wang1,2, Ting Lu1, Yali Gui1
1Department of Anesthesiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Translational psychiatry
|August 14, 2023
概括
热冲击蛋白A12A (HSPA12A) 通过维持大脑乳酸平衡来调节情绪稳定. 失去HSPA12A会损害神经发生并导致情绪不稳定,但乳酸盐的使用对情绪障碍具有治疗潜力.
科学领域:
- 神经科学是一个神经科学.
- 精神病学是一个精神病学.
- 分子生物学分子生物学
背景情况:
- 情绪不稳定是主要抑郁症和双相情感障碍的一个关键症状.
- 在精神分裂症患者中,热冲击蛋白A12A (HSPA12A) 的表达减少.
- 对于HSPA12A在精神疾病中的确切作用尚不清楚.
研究的目的:
- 调查HSPA12A对情绪稳定的因果关系.
- 探索涉及大脑乳酸和神经发生的潜在机制.
- 评估HSPA12A在情绪调节方面的治疗潜力.
主要方法:
- 使用了Hspa12a淘汰赛小鼠和野生类型的 littermates.
- 使用开放场地,强迫游泳,升高加迷宫和糖糖偏好测试来评估行为表型.
- 通过BrdU标记测量了CSF和成人海马神经发生 (AHN) 中的大脑乳酸盐水平.
主要成果:
- Hspa12a淘汰赛的小鼠表现出情绪不稳定,AHN受损,脑液中乳酸水平降低.
- 神经元中的HSPA12A过度表达增加了乳酸盐的产生和糖解酶的表达.
- 乳酸盐的使用改善了麻小鼠的情绪不稳定性和AHN缺陷.
结论:
- HSPA12A对于维持大脑乳酸平衡和情绪稳定至关重要.
- HSPA12A通过抑制海马神经元中的GSK3β而起作用,支持AHN和情绪调节.
- HSPA12A代表了情绪障碍的新型治疗标.
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