Key Laboratory of CNS Regeneration (Ministry of Education), Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, 510600 Guangzhou, China.
College of Life Science and Technology, Jinan University, 510600 Guangzhou, China.
Cell Metab. 2024 Sep 3;36(9):2104-2117.e4. doi: 10.1016/j.cmet.2024.07.018. Epub 2024 Aug 19.
Lactate is a critical metabolite during the body's adaption to exercise training, which effectively relieves anxiety-like disorders. The biological mechanism of lactate in the exercise-mediated anxiolytic effect has, however, not been comprehensively investigated. Here, we report that exercise-induced lactate markedly potentiates the lactylation of multiple synaptic proteins, among which synaptosome-associated protein 91 (SNAP91) is the critical molecule for synaptic functions. Both anatomical evidence and in vivo recording data showed that the lactylation of SNAP91 confers resilience against chronic restraint stress (CRS) via potentiating synaptic structural formation and neuronal activity in the medial prefrontal cortex (mPFC). More interestingly, exercise-potentiated lactylation of SNAP91 is necessary for the prevention of anxiety-like behaviors in CRS mice. These results collectively suggest a previously unrecognized non-histone lactylation in the brain for modulating mental functions and provide evidence for the brain's metabolic adaption during exercise paradigms.
乳酸是机体适应运动训练的关键代谢物，能有效缓解焦虑样障碍。然而，运动介导的抗焦虑作用中乳酸的生物学机制还没有被全面研究。在这里，我们报告运动诱导的乳酸显著增强了多种突触蛋白的乳酰化作用，其中突触小体相关蛋白 91（SNAP91）是突触功能的关键分子。解剖学证据和体内记录数据表明，SNAP91 的乳酰化通过增强内侧前额叶皮质（mPFC）中的突触结构形成和神经元活动，赋予对慢性束缚应激（CRS）的抵抗能力。更有趣的是，运动增强的 SNAP91 乳酰化对于预防 CRS 小鼠的焦虑样行为是必要的。这些结果共同表明，大脑中存在一种以前未被识别的非组蛋白乳酰化，可调节精神功能，并为运动范式下大脑的代谢适应提供证据。
