The brain, circadian rhythms, and clock genesBMJ 1998; 317 doi: https://doi.org/10.1136/bmj.317.7174.1704 (Published 19 December 1998) Cite this as: BMJ 1998;317:1704
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Hastings (1) seems to have missed a vital point in the ticking of the
biological clock. Biological rhythms are a fundamental feature of all
living organisms. Most of these rhythms are synchronised by the 24 - hour
light/day (L/D) cycle so that our physiological and biochemical functions
as wel as behaviors follow a 24 hour rhythmicity. Some rhythms also
display annual variations. The self-sustaining oscillatory activity of the
circadian clocks is synchronised by the L/D cycle. In mammals, the clock,
which is situated in the suprachiasmatic nuclei of the hypothalamus,
receives input from the retina. Melatonin, produced in the pineal gland,
is now considered to be the time-keeping molecule of the circadian clock.
It has been suggested that the clock machinery resides in the
photoreceptor, and that each photoreceptor may be a cellular circadian
system in itself (2). Studies have also shown that retinal and pineal
photoreceptors possess voltage-gated dihydropyridine-sensitive calcium
channels which open in the dark, allowing entry of calcium into the cell
and contributing to a stimulation of melatonin production, in part through
the modulation of cAMP production (3).
The circadian clock may tick quite late in life too. Melatonin levels
are found to decrease with age (4) and the ability of the pineal gland to
produce and release melatonin vaies greatly with age (5). Elderly patients
who suffer from Seasonal Affective Disorders (SAD) become depressed during
times of the year when daylight hours are diminished. Therapy using high
intensity light has proven to increase melatonin production and to relieve
these feelings of depression. Melatonin is an inexpensive and non-toxic
non-prescription substance which is available over the counter in the US.
Interestingly, melatonin has also been used effectively and safely in low
doses to treat insomnia in elderly patients (6).
Surely the Drosophila does not know that there is more to the
biological clock than meets the brain!
1. Hastings M. The brain, circadian rhythm and clock genes. BMJ.
1998; 317: 1704-07
2. Bolliet V, Bejay V, Taraquat C, et al. The photoreceptor cell of the
pike pineal organ as a cellular circadian system. Eur. J Neurosci. 1997;
3. Bejay V, Collin JP, Falcon J. Calciproteins regulate cyclic AMP content
and melatonin secretion in trout pineal photoreceptors. Neuroreport. 1994;
4. Reiter RJ, Ricjardson BA, Johnson CY, et al. Pineal melatonin rhythm:
reduction in agingSrian Hamsters. Science, 1980; 210: 1372-73
5. Reiter RJ. The aging pineal gland and its physiological consequences.
BioEssays. 1992; 14: 169-75
6. Amazing medicines the drug companies don't want you to discover.
University Medical Research Publishers, empe, Arizona: 1993; p73
Competing interests: No competing interests