Differential role of melatonin in restoration of age-induced alterations in daily rhythms of expression of various clock genes in suprachiasmatic nucleus of male Wistar rats

Abstract

Aging is associated with changes in several basic parameters of circadian rhythms in mammals leading to circadian dysfunction. The hypothalamic Suprachiasmatic nucleus (SCN) regulates neuronal, endocrine and behavioral rhythms through the expression of various clock genes and release of melatonin from pineal gland. In the present study, we investigated the effect of aging on daily rhythms of various clock genes such as rPer1, rPer2, rCry1, rCry2 and rBmal1 in the SCN of male Wistar rats. The m-RNA expression levels of these genes were studied by using quantitative Polymerase Chain Reaction (qPCR) in 3 age groups [3 (adult), 12 and 24month (m)] at variable time points (Zeitgeber time (ZT)-0, 6, 12 and 18). The m-RNA expression for all genes studied was rhythmic in SCN of adult rats with maximum for rPer1 at ZT-6, rPer2, rCry1 and rCry2 at ZT-12 and rBmal1 at ZT-18. However in 12 and 24m, the phases of expression of these genes were significantly altered with abolition of daily rhythms of rCry1, rCry2 and rBmal1 in 24m. Melatonin, messenger of darkness, an endogenous synchronizer of rhythm, an antioxidant and an antiaging drug, declines with aging. We therefore studied the effects of melatonin administered subcutaneously at 1h before the onset of darkness (ZT-11) for 11days on age induced desynchronization in expression of these genes. We report here differential restoration of daily rhythm, phase, levels and stoichiometric interaction of m-RNA expression of these genes in various age groups in rat SCN with melatonin treatment.