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| Astrocytic lactate dehydrogenase A regulates neuronal excitability and depressive-like behaviors through lactate homeostasis in mice | |
| 2023-02 | |
| Source Publication | NATURE COMMUNICATIONS
 |
| ISSN | 2041-1723 |
| EISSN | 2041-1723 |
| Volume | 14Issue:1 |
| Status | 已发表 |
| DOI | 10.1038/s41467-023-36209-5 |
| Abstract | ["The role of glycolysis in depression is unclear. Here the authors report a glycolytic deficit under social stress and demonstrate that astrocytic LDHA affects neuronal excitability and depressive-like behaviours via lactate homeostasis in mice.","Alterations in energy metabolism are associated with depression. However, the role of glycolysis in the pathogenesis of depression and the underlying molecular mechanisms remain unexplored. Through an unbiased proteomic screen coupled with biochemical verifications, we show that the levels of glycolysis and lactate dehydrogenase A (LDHA), a glycolytic enzyme that catalyzes L-lactate production, are reduced in the dorsomedial prefrontal cortex (dmPFC) of stress-susceptible mice in chronic social defeat stress (CSDS) model. Conditional knockout of LDHA from the brain promotes depressive-like behaviors in both male and female mice, accompanied with reduced L-lactate levels and decreased neuronal excitability in the dmPFC. Moreover, these phenotypes could be duplicated by knockdown of LDHA in the dmPFC or specifically in astrocytes. In contrast, overexpression of LDHA reverses these phenotypic changes in CSDS-susceptible mice. Mechanistic studies demonstrate that L-lactate promotes neuronal excitability through monocarboxylic acid transporter 2 (MCT2) and by inhibiting large-conductance Ca2+-activated potassium (BK) channel. Together, these results reveal a role of LDHA in maintaining neuronal excitability to prevent depressive-like behaviors."] |
| URL | 查看原文 |
| Indexed By | SCOPUS ; SCI |
| Language | 英语 |
| Funding Project | Natural Science Foundation of China["82271555","91949117","31871044","32100822"] ; Natural Science Foundation of Guangdong["2020B1515020006","2017A030310157"] |
| WOS Research Area | Science & Technology - Other Topics |
| WOS Subject | Multidisciplinary Sciences |
| WOS ID | WOS:001023549000013 |
| Publisher | NATURE PORTFOLIO |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/276764 |
| Collection | 生命科学与技术学院 生命科学与技术学院_PI研究组_李磊组 |
| Corresponding Author | Sun, Xiang-Dong |
| Affiliation | 1.Guangzhou Med Univ, Affiliated Hosp 2, Inst Neurosci, Dept Neurol,Key Lab Neurogenet & Channelopathies G, Guangzhou 510260, Peoples R China 2.Guangzhou Med Univ, Sch Basic Med Sci, Minist Educ China, Guangzhou 510260, Peoples R China 3.Guangzhou Med Univ, Sch Basic Med Sci, Dept Physiol, Guangzhou 511436, Peoples R China 4.Guangxi Univ Sci & Technol, Dept Physiol, Liuzhou 545005, Peoples R China 5.Nanchang Univ, Inst Life Sci, Nanchang 330031, Peoples R China 6.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China |
| Recommended Citation GB/T 7714 | Yao, Shan,Xu, Min-Dong,Wang, Ying,et al. Astrocytic lactate dehydrogenase A regulates neuronal excitability and depressive-like behaviors through lactate homeostasis in mice[J]. NATURE COMMUNICATIONS,2023,14(1). |
| APA | Yao, Shan.,Xu, Min-Dong.,Wang, Ying.,Zhao, Shen-Ting.,Wang, Jin.,...&Sun, Xiang-Dong.(2023).Astrocytic lactate dehydrogenase A regulates neuronal excitability and depressive-like behaviors through lactate homeostasis in mice.NATURE COMMUNICATIONS,14(1). |
| MLA | Yao, Shan,et al."Astrocytic lactate dehydrogenase A regulates neuronal excitability and depressive-like behaviors through lactate homeostasis in mice".NATURE COMMUNICATIONS 14.1(2023). |
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