International Journal of Molecular Zoology 2024, Vol.14, No.3, 166-181 http://animalscipublisher.com/index.php/ijmz 169 3 Physiological Mechanisms of Circadian Rhythms 3.1 Neural pathways involved in circadian regulation The central pacemaker of the mammalian circadian timing system is located in the suprachiasmatic nuclei (SCN) of the hypothalamus. This master clock coordinates the timing of oscillators throughout the brain and body, ensuring synchronization with the external environment, primarily through light-dark (LD) cycles (Mohawk et al., 2012; Eckel-Mahan and Sassone-Corsi, 2013; Panda, 2016). The SCN receives photic information from the retina via the retinohypothalamic tract, which transmits signals through neurotransmitters such as glutamate and pituitary adenylate cyclase-activating polypeptide (PACAP) (Eckel-Mahan and Sassone-Corsi, 2013). These signals activate intracellular pathways in SCN neurons, leading to changes in clock gene expression and neuronal activity (Eckel-Mahan and Sassone-Corsi, 2013; Pitsillou et al., 2020). Additionally, the SCN communicates with peripheral clocks through both neuronal and humoral pathways, ensuring that physiological processes are synchronized across the entire organism (Panda, 2016; Pitsillou et al., 2020; Guan and Lazar, 2021). The SCN's ability to integrate external light information and adapt cellular clocks in all tissues is crucial for maintaining circadian rhythms (Pitsillou et al., 2020). 3.2 Hormonal control of circadian rhythms Hormones play a significant role in the regulation of circadian rhythms, acting as mediators between the central clock and peripheral tissues. The SCN influences the release of various hormones, including melatonin, cortisol, and insulin, which help synchronize peripheral clocks with the central pacemaker (Panda, 2016; Pitsillou et al., 2020; Guan and Lazar, 2021). Melatonin, produced by the pineal gland, is a well-known marker of circadian rhythms and is regulated by the SCN through sympathetic nervous system pathways (Panda, 2016). Cortisol, a glucocorticoid hormone, follows a circadian pattern with peak levels in the early morning, driven by the SCN's influence on the hypothalamic-pituitary-adrenal (HPA) axis (Panda, 2016; Pitsillou et al., 2020). Insulin secretion is also under circadian control, with the SCN modulating pancreatic function to align glucose metabolism with feeding cycles. These hormonal signals ensure that physiological processes such as sleep-wake cycles, metabolism, and immune function are appropriately timed with the external environment (Eckel-Mahan and Sassone-Corsi, 2013; Pitsillou et al., 2020; Guan and Lazar, 2021). 3.3 Interaction between circadian rhythms and metabolic processes Circadian rhythms are intricately linked with metabolic processes, with the central clock in the SCN coordinating metabolic functions across various tissues. The SCN regulates feeding-fasting cycles, energy expenditure, and glucose homeostasis through its influence on peripheral clocks in organs such as the liver, pancreas, and adipose tissue (Mohawk et al., 2012; Tsang et al., 2013; Guan and Lazar, 2021). Clock genes, such as Period (PER) and Cryptochrome (CRY), play a crucial role in this regulation by modulating the expression of genes involved in metabolic pathways8 9. For instance, the clock component PER2 interacts with nuclear receptors like PPARalpha and REV-ERBalpha, coordinating the expression of genes involved in glucose metabolism and lipid homeostasis (Asher and Schibler, 2011). Disruptions in circadian rhythms can lead to metabolic disorders, highlighting the importance of maintaining synchrony between the central clock and peripheral metabolic processes (Asher and Schibler, 2011; Robles et al., 2017). Recent studies have also shown that redox reactions and transcriptional loops are interconnected, further linking circadian rhythms with metabolic regulation (Robles et al., 2017). Understanding these interactions is essential for developing therapeutic strategies to address metabolic diseases associated with circadian disruption (Asher and Schibler, 2011; Robles et al., 2017). The physiological mechanisms of circadian rhythms involve complex interactions between neural pathways, hormonal signals, and metabolic processes. The SCN serves as the central pacemaker, integrating external light information and coordinating peripheral clocks through neuronal and humoral pathways. Hormones such as melatonin, cortisol, and insulin play crucial roles in synchronizing physiological processes with the central clock. Additionally, circadian rhythms are tightly linked with metabolic functions, with clock genes modulating the expression of genes involved in metabolism. Disruptions in these mechanisms can lead to various health issues, emphasizing the importance of maintaining circadian synchrony.
RkJQdWJsaXNoZXIy MjQ4ODYzNA==