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Review
. 2023 Jan 19:16:1059229.
doi: 10.3389/fncir.2022.1059229. eCollection 2022.

Circadian rhythms as modulators of brain health during development and throughout aging

Rachel Van Drunen  1 , Kristin Eckel-Mahan  1
Affiliations
Review

Circadian rhythms as modulators of brain health during development and throughout aging

Rachel Van Drunen et al. Front Neural Circuits. .

Abstract

The circadian clock plays a prominent role in neurons during development and throughout aging. This review covers topics pertinent to the role of 24-h rhythms in neuronal development and function, and their tendency to decline with aging. Pharmacological or behavioral modification that augment the function of our internal clock may be central to decline of cognitive disease and to future chronotherapy for aging-related diseases of the central nervous system.

Keywords: aging; chronotherapy; circadian; memory; suprachiasmatic nucleus; synaptic plasticity.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Circadian rhythms across the body are entrained by the 24-h environment. Diurnal light exposure entrains the “master clock”, known as the suprachiasmatic nucleus (SCN). The SCN coordinates daily rhythms in the brain as well as the periphery via a combination of neuronal signals and hormones, including cortisol and melatonin, which fluctuate opposite to each other and promote sleep/wake cycles. At the cellular level, the core transcription translational feedback loop in the nucleus is characterized by BMAL1 and CLOCK binding to E-box containing genes to regulate transcription of numerous clock controlled genes (CCGs) including their own repressors, PERIOD (PER) and CRYPTOCHROME (CRY). Heterodimers PER and CRY translocate back into the nucleus to inhibit the CLOCK:BMAL1 complex, thereby inhibiting their own production.
FIGURE 2
FIGURE 2
The development of the circadian system is initiated prior to birth. Between 18 and 24 weeks of age, melatonin and dopamine receptors are detectable in the SCN. Soon after birth, many entrainment cues are passed to the baby through breast milk. At 8 weeks of age, cortisol rhythms have emerged in the infant, and by 14 weeks of age, most babies show a diurnal sleep pattern. Finally, at 9 months of age, the baby is thought to have a fully functional SCN.
FIGURE 3
FIGURE 3
Synaptic mechanisms under circadian control. Glutamate released from the presynaptic terminal binds to NMDA and AMPA receptors stimulating an influx of Na+ and Ca2+, respectively. Ca2+- activated adenylyl cyclases lead to increased cAMP, ultimately resulting in CREB phosphorylation and activation of gene transcription. This pathway is both light-responsive in the SCN and under circadian control in the hippocampus, where it regulates learning and memory. Meanwhile the clock-controlled gene, GSK3β, regulates post-synaptic dendritic growth. Astrocytes play an important role in circadian timing in the SCN, where their circadian nighttime activity suppresses activity of SCN neurons by regulation of extrasynaptic glutamate levels. Intracellular calcium levels in astrocytes are also highly dynamic over the 24-h cycle.
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