Sleep Research Laboratory, Eastern Virginia Medical School, Norfolk, VA, USA.
Center for Integrative Neuroscience and Inflammatory Diseases, Eastern Virginia Medical School, Norfolk, VA, USA.
Sci Prog. 2024 Apr-Jun;107(2):368504241253692. doi: 10.1177/00368504241253692.
The brain regulates every physiological process in the body, including metabolism. Studies investigating brain metabolism have shown that stress can alter major metabolic processes, and that these processes can vary between regions. However, no study has investigated how metabolic pathways may be altered by stressor perception, or whether stress-responsive brain regions can also regulate metabolism. The basolateral amygdala (BLA), a region important for stress and fear, has reciprocal connections to regions responsible for metabolic regulation. In this study, we investigated how BLA influences regional metabolic profiles within the hippocampus (HPC) and medial prefrontal cortex (mPFC), regions involved in regulating the stress response and stress perception, using optogenetics in male C57BL/6 mice during footshock presentation in a yoked shuttlebox paradigm based on controllable (ES) and uncontrollable (IS) stress. RNA extracted from HPC and mPFC were loaded into NanoString® Mouse Neuroinflammation Panels, which also provides a broad view of metabolic processes, for compilation of gene expression profiles. Results showed differential regulation of carbohydrate and lipid metabolism, and insulin signaling gene expression pathways in HPC and mPFC following ES and IS, and that these differences were altered in response to optogenetic excitation or inhibition of the BLA. These findings demonstrate for the first time that individual brain regions can utilize metabolites in a way that are unique to their needs and function in response to a stressor, and that vary based on stressor controllability and influence by BLA.
大脑调节着身体的每一个生理过程，包括新陈代谢。研究大脑代谢的研究表明，压力可以改变主要的代谢过程，而且这些过程在不同的区域之间是不同的。然而，没有研究调查过代谢途径可能如何被压力感知改变，或者应激反应性大脑区域是否也能调节代谢。外侧杏仁核（BLA）是一个与压力和恐惧有关的区域，它与负责代谢调节的区域有相互联系。在这项研究中，我们使用光遗传学方法，在可控（ES）和不可控（IS）应激的基于配对穿梭箱范式的足部电击中，研究了 BLA 如何影响海马体（HPC）和内侧前额叶皮层（mPFC）内的区域代谢特征，这两个区域参与调节应激反应和应激感知。从 HPC 和 mPFC 中提取的 RNA 被加载到 NanoString®小鼠神经炎症面板上，该面板还提供了代谢过程的广泛视图，用于编译基因表达谱。结果表明，在 ES 和 IS 后，HPC 和 mPFC 中的碳水化合物和脂质代谢以及胰岛素信号基因表达途径的差异调节，并且这些差异响应于 BLA 的光遗传学兴奋或抑制而改变。这些发现首次表明，单个大脑区域可以以一种与其需求和功能相适应的独特方式利用代谢物来应对压力源，并且这种方式还因压力源的可控性和 BLA 的影响而有所不同。
