Aging abolishes circadian rhythms and disrupts temporal organization of antioxidant-prooxidant status, endogenous clock activity and neurotrophin gene expression in the rat temporal cortex

Neuroscience. 2024 Nov 1:559:125-138. doi: 10.1016/j.neuroscience.2024.09.008. Epub 2024 Sep 5.

Abstract

Disruption of circadian rhythms contributes to deficits in cognitive functions during aging. Up to date, the biochemical, molecular and chronobiological bases of such deterioration have not been completely elucidated. Here, we aim: 1) to investigate the endogenous nature of 24 h-rhythms of antioxidant defenses, oxidative stress, clocḱ's, and neurotrophic factors expression, in the rat temporal cortex (TC), and 2) to study the consequences of aging on the circadian organization of those factors. We observed a circadian organization of antioxidant enzymes activity, lipoperoxidation and the clock, BMAL1 and RORa, proteins, in the TC of young rats. Such temporal organization suggests the existence of a two-way communication among clock transcription factors and antioxidant defenses. This might generate the rhythmic and circadian expression of Bdnf and Rc3 genes involved in the TC-depending cognitive function. Noteworthy, such circadian organization disappears in the TC of aged rats. Aging also reduces glutathione peroxidase activity and expression, and it increases lipid peroxidation, throughout a 24 h-period. An increased oxidative stress makes the cellular redox environment change into an oxidative status which alters the endogenous clock activity and disrupts the circadian organization of, at least part, of the molecular basis of the synaptic plasticity in the TC.

Keywords: Aging; Antioxidant Enzyme; Bdnf; Circadian Rhythm; Rc3; Temporal Cortex.

MeSH terms

  • ARNTL Transcription Factors* / genetics
  • ARNTL Transcription Factors* / metabolism
  • Aging* / metabolism
  • Aging* / physiology
  • Animals
  • Antioxidants / metabolism
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism
  • CLOCK Proteins* / genetics
  • CLOCK Proteins* / metabolism
  • Circadian Rhythm* / physiology
  • Gene Expression
  • Glutathione Peroxidase / genetics
  • Glutathione Peroxidase / metabolism
  • Lipid Peroxidation* / physiology
  • Male
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / metabolism
  • Nuclear Receptor Subfamily 1, Group F, Member 1 / genetics
  • Nuclear Receptor Subfamily 1, Group F, Member 1 / metabolism
  • Oxidative Stress* / physiology
  • Rats
  • Rats, Wistar*
  • Temporal Lobe* / metabolism

Substances

  • CLOCK Proteins
  • ARNTL Transcription Factors
  • Brain-Derived Neurotrophic Factor
  • Antioxidants
  • Glutathione Peroxidase
  • Nerve Growth Factors
  • Arntl protein, rat
  • Nuclear Receptor Subfamily 1, Group F, Member 1
  • Clock protein, rat