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

Biogerontology. 2014 Jun;15(3):257-68. doi: 10.1007/s10522-014-9495-2. Epub 2014 Mar 12.


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 24 month (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 24 m, the phases of expression of these genes were significantly altered with abolition of daily rhythms of rCry1, rCry2 and rBmal1 in 24 m. 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 1 h before the onset of darkness (ZT-11) for 11 days 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors / genetics*
  • ARNTL Transcription Factors / metabolism
  • Aging / physiology*
  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / physiology
  • Circadian Rhythm / drug effects
  • Circadian Rhythm / genetics
  • Circadian Rhythm / physiology*
  • Circadian Rhythm Signaling Peptides and Proteins / genetics*
  • Circadian Rhythm Signaling Peptides and Proteins / metabolism
  • Cryptochromes / genetics
  • Cryptochromes / metabolism
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Male
  • Melatonin / pharmacology
  • Melatonin / physiology*
  • Morphinans / metabolism
  • Period Circadian Proteins / genetics
  • Period Circadian Proteins / metabolism
  • Rats, Wistar
  • Suprachiasmatic Nucleus / metabolism
  • Suprachiasmatic Nucleus / physiology*


  • ARNTL Transcription Factors
  • Antioxidants
  • Circadian Rhythm Signaling Peptides and Proteins
  • Cry1 protein, rat
  • Cry2 protein, rat
  • Cryptochromes
  • Morphinans
  • Per1 protein, rat
  • Per2 protein, rat
  • Period Circadian Proteins
  • Mr 1257 MS
  • Melatonin