乳酸酸的急性管理通过cAMP依赖的蛋白质合成产生抗抑郁药效应
Liang Zhang1, Jing Zheng2, Shi-Yan Liu2
1Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Faculty of Basic Medical Sciences, Guilin Medical University, Guilin, Guangxi 541199, China; Department of Anesthesiology, National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, Shenzhen, Guangdong 518112, China; Department of Anesthesiology, Nanhua Affiliated Hospital, University of South China, Hengyang, Hunan 421001, China.
急性乳酸输液通过循环腺单酸盐 (cAMP) 途径促进脑衍生神经营养因子 (BDNF) 蛋白质合成,独立于基因表达或HCAR1激活,显示抗抑郁作用.
科学领域:
- 神经科学是一个神经科学.
- 生物化学 生物化学
- 药理学 药理学是指药理学的学科.
背景情况:
- 乳酸是大脑中重要的代谢基质和信号分子.
- 以前的研究表明,外周乳酸剂的使用具有抗抑郁作用.
- 急性乳酸的抗抑郁作用的精确神经机制仍然不清楚.
研究的目的:
- 为了研究激烈抗抑郁药效应的基础的神经机制的脑内静脉 (ICV) 乳酸输液.
- 阐明涉及乳酸诱导抗抑郁药效应的分子途径.
主要方法:
- 在238只雄性Sprague Dawley大鼠中使用强迫游泳测试 (FST).
- 通过ICV输注给予乳酸.
- 评估剂量和时间依赖性,蛋白质合成,基因表达,代谢效应和HCAR1激活.
- 在海马体中测量了真核延长因子2 (eEF2) 脱化和来自大脑的神经营养因子 (BDNF) 蛋白质合成.
- 研究了循环腺单酸盐 (cAMP) 信号传输的作用.
主要成果:
- 乳酸氨酸表现出剂量和时间依赖的抗抑郁药类效果,降低了FST的不运动性.
- 抗抑郁药的效果取决于新的蛋白质合成,而不是新的基因表达,代谢效应或HCAR1激活.
- 乳糖酸迅速通过eEF2脱化以cAMP依赖的方式在海马体中增加BDNF蛋白质合成.
- 抑制cAMP的产生取消了乳酸的抗抑郁药效应.
结论:
- 急性脑内静脉乳酸剂的使用会产生类似抗抑郁药的效果.
- 该机制涉及cAMP依赖的蛋白质合成,特别是在海马中促进BDNF的产生.
- 这一途径独立于基因表达,乳酸的直接代谢作用或HCAR1信号传递.
更多相关视频
10:45Simultaneous Electroencephalography, Real-time Measurement of Lactate Concentration and Optogenetic Manipulation of Neuronal Activity in the Rodent Cerebral Cortex
Published on: December 19, 2012
09:51Recording Synaptic Plasticity in Acute Hippocampal Slices Maintained in a Small-volume Recycling-, Perfusion-, and Submersion-type Chamber System
Published on: January 1, 2018
相关概念视频
Long-term Depression
Calcium Ion Concentration Mechanism
If over...
Long-term Potentiation
Hebbian LTP
LTP can occur when...
Muscle Recovery and Fatigue
Ligand-Gated Ion Channel Receptor: Gating Mechanism
cAMP-dependent Protein Kinase Pathways
Local Anesthetics: Mechanism of Action
Local anesthetics are amphiphilic molecules consisting of a hydrophobic aromatic part linked to a hydrophilic group by an ester or amide linkage. They are weak bases and are usually available as salts, which increases their solubility and stability. Once administered, LAs exist in the body either...
