Neurobiology and Molecular Chronobiology Laboratory, Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana, 500046, India.
Biogerontology. 2024 Nov 15;26(1):9. doi: 10.1007/s10522-024-10150-6.
The suprachiasmatic nucleus (SCN) in the hypothalamus regulates circadian timing system (CTS) by co-ordinating peripheral tissue clocks and extra-SCN oscillators in the brain. Aging disrupts the CTS, impairing physiological functions and reducing antioxidant defences, which contribute to neurodegeneration. The brain is vulnerable to oxidative damage due to its high metabolic activity, oxygen consumption, and levels of iron and lipids. Antioxidant enzymes, such as catalase (CAT), glutathione S-transferase (GST), superoxide dismutase (SOD), and lipid peroxidation (LPO), help against oxidative damage. In this study, we examined the temporal patterns of these antioxidant stress indicators in the SCN and extra-SCN brain regions (frontal cortex, cerebellum, and hippocampus) at various time points in male Wistar rats 3, 12, and 24 months. The rhythmicity of GST and LPO levels persisted across brain regions with aging, while CAT rhythmicity was lost in the SCN and hippocampus of older rats. SOD rhythmicity persisted in cortex, cerebellum, and hippocampus but was lost in the SCN. The daily rhythm parameters of CAT were affected most significantly, followed by SOD, GST, and LPO. Our findings demonstrate that aging leads to desynchronization of oxidative stress indicators potentially contributing to neurodegeneration and circadian dysfunction with varying effects across different brain tissues.
视交叉上核（SCN）位于下丘脑，通过协调外周组织时钟和大脑中的 SCN 振荡器来调节昼夜节律系统（CTS）。衰老会破坏 CTS，损害生理功能并降低抗氧化防御能力，从而导致神经退行性变。由于大脑代谢活动高、耗氧量高、铁和脂质水平高，因此容易受到氧化损伤。抗氧化酶，如过氧化氢酶（CAT）、谷胱甘肽 S-转移酶（GST）、超氧化物歧化酶（SOD）和脂质过氧化（LPO），有助于对抗氧化损伤。在这项研究中，我们检查了雄性 Wistar 大鼠在 3、12 和 24 个月时不同时间点 SCN 和大脑外 SCN 区域（额叶皮层、小脑和海马体）中这些抗氧化应激指标的时间模式。随着年龄的增长，GST 和 LPO 水平的节律性在大脑区域中持续存在，而 CAT 节律性在老年大鼠的 SCN 和海马体中丧失。SOD 节律性在皮层、小脑和海马体中持续存在，但在 SCN 中丧失。CAT 的昼夜节律参数受到的影响最为显著，其次是 SOD、GST 和 LPO。我们的研究结果表明，衰老会导致氧化应激指标失同步，可能导致神经退行性变和昼夜节律功能障碍，不同的大脑组织受到的影响不同。
