Aging changes the expression of adenosine receptors, insulin-like growth factor 1 (IGF1), and hypoxia-inducible factor 1α (HIF1α) in hypothalamic astrocyte cultures

IF 1.7 Q3 CLINICAL NEUROLOGY Aging brain Pub Date : 2023-12-23 DOI:10.1016/j.nbas.2023.100104
Camila Leite Santos , Larissa Daniele Bobermin , André Quincozes-Santos
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Abstract

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.

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衰老会改变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 (IGF1) 和缺氧诱导因子 1α (HIF1α) 的表达
衰老过程会诱发包括下丘脑在内的不同脑区的神经化学变化。中枢神经系统(CNS)的这一关键区域对于检测和整合来自身体外围的营养和激素信号以维持代谢平衡至关重要。星形胶质细胞支持中枢神经系统的平衡、能量代谢和炎症反应,越来越多的证据表明星形胶质细胞在协调下丘脑功能和神经胶质系统中发挥着关键作用。在这项研究中,我们旨在研究新生大鼠、成年大鼠和老龄大鼠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mRNA表达以及IGF1和HIF1α的水平随年龄的变化。我们的研究结果表明,腺苷受体的变化与年龄有关,IGF1R/IGF1 和 HIF1α 的变化也与年龄有关。值得注意的是,腺苷受体、IGF1和HIF1α会受到炎症、氧化还原和新陈代谢过程的影响,这些过程会重塑下丘脑的特性,正如在衰老大脑中观察到的那样,这加强了下丘脑星形胶质细胞作为了解与年龄相关疾病的发生和/或进展的靶标的作用。
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Aging brain
Aging brain Neuroscience (General), Geriatrics and Gerontology
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