Francés Raquel, Rabah Yasmine, Preat Thomas, Plaçais Pierre-Yves
Energy & Memory, Brain Plasticity (UMR 8249), CNRS, ESPCI Paris, PSL Research University, Paris, France.
Nat Commun. 2024 Dec 2;15(1):10467. doi: 10.1038/s41467-024-54778-x.
An essential role of glial cells is to comply with the large and fluctuating energy needs of neurons. Metabolic adaptation is integral to the acute stress response, suggesting that glial cells could be major, yet overlooked, targets of stress hormones. Here we show that Dh44 neuropeptide, Drosophila homologue of mammalian corticotropin-releasing hormone (CRH), acts as an experience-dependent metabolic switch for glycolytic output in glia. Dh44 released by dopamine neurons limits glial fatty acid synthesis and build-up of lipid stores. Although basally active, this hormonal axis is acutely stimulated following learning of a danger-predictive cue. This results in transient suppression of glial anabolic use of pyruvate, sparing it for memory-relevant energy supply to neurons. Diverting pyruvate destination may dampen the need to upregulate glial glycolysis in response to increased neuronal demand. Although beneficial for the energy efficiency of memory formation, this mechanism reveals an ongoing competition between neuronal fuelling and glial anabolism.
神经胶质细胞的一个重要作用是满足神经元对能量的巨大且波动的需求。代谢适应是急性应激反应不可或缺的一部分，这表明神经胶质细胞可能是应激激素的主要但被忽视的靶点。在这里，我们表明Dh44神经肽，即哺乳动物促肾上腺皮质激素释放激素（CRH）的果蝇同源物，作为神经胶质细胞糖酵解输出的经验依赖性代谢开关。多巴胺神经元释放的Dh44限制了神经胶质细胞脂肪酸的合成和脂质储存的积累。尽管该激素轴在基础状态下就有活性，但在学习到危险预测线索后会被急性刺激。这导致神经胶质细胞对丙酮酸的合成代谢利用暂时受到抑制，从而将其节省下来用于为与记忆相关的神经元提供能量。改变丙酮酸的去向可能会减少因神经元需求增加而上调神经胶质细胞糖酵解的必要性。尽管这对记忆形成的能量效率有益，但这种机制揭示了神经元供能与神经胶质细胞合成代谢之间持续存在的竞争。
