Santos Camila Leite, Bobermin Larissa Daniele, Quincozes-Santos André
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Aging Brain. 2023 Dec 23;5:100104. doi: 10.1016/j.nbas.2023.100104. eCollection 2024.
The aging process induces neurochemical alterations in different brain regions, including hypothalamus. This pivotal area of the central nervous system (CNS) is crucial for detection and integration of nutritional and hormonal signals from the periphery of the body to maintain metabolic homeostasis. Astrocytes support the CNS homeostasis, energy metabolism, and inflammatory response, as well as increasing evidence has highlighted a critical role of astrocytes in orchestrating hypothalamic functions and in gliocrine system. In this study, we aimed to investigate the age-dependent mRNA expression of adenosine receptors, the insulin-like growth factor 1 receptor (IGF1R), and the hypoxia-inducible factor 1α (HIF1α), in addition to the levels of IGF1 and HIF1α in hypothalamic astrocyte cultures derived from newborn, adult, and aged rats. Our results revealed age-dependent changes in adenosine receptors, as well as a decrease in IGF1R/IGF1 and HIF1α. Of note, adenosine receptors, IGF1, and HIF1α are affected by inflammatory, redox, and metabolic processes, which can remodel hypothalamic properties, as observed in aging brain, reinforcing the role of hypothalamic astrocytes as targets for understanding the onset and/or progression of age-related diseases.
衰老过程会在包括下丘脑在内的不同脑区引发神经化学变化。中枢神经系统（CNS）的这个关键区域对于检测和整合来自身体外周的营养和激素信号以维持代谢稳态至关重要。星形胶质细胞支持中枢神经系统的稳态、能量代谢和炎症反应，而且越来越多的证据表明星形胶质细胞在协调下丘脑功能和胶质细胞分泌系统中起着关键作用。在本研究中，我们旨在调查源自新生、成年和老年大鼠的下丘脑星形胶质细胞培养物中腺苷受体、胰岛素样生长因子1受体（IGF1R）和缺氧诱导因子1α（HIF1α）的年龄依赖性mRNA表达，以及IGF1和HIF1α的水平。我们的结果揭示了腺苷受体的年龄依赖性变化，以及IGF1R/IGF1和HIF1α的减少。值得注意的是，腺苷受体、IGF1和HIF1α受炎症、氧化还原和代谢过程的影响，这些过程可重塑下丘脑特性，如在衰老大脑中观察到的那样，这强化了下丘脑星形胶质细胞作为理解与年龄相关疾病的发病和/或进展的靶点的作用。
