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Body and mind

Flaw in our internal clock can make us depressed

Of all the clocks we humans surround ourselves with, our internal clock is probably the most important. This helps to synchronize our biological functions with the astronomical day. Researchers have now studied the molecular mechanics of our internal clock and discovered that a flaw in part of our molecular clock can make us depressed.

The human internal rhythm based on a 24-hour cycle is called the circadian rhythm. This ensures that we are tired when it gets dark and refreshed when dawn breaks. The eyes are the window that filters light into the cerebral clock. If it malfunctions, we can get sick. Because of its central location and function, we still do not know the molecular mechanics that ensure that our clock works as it should. A Danish research group has discovered more about this.

In humans and other mammals, this central clock is in the hypothalamus in the diencephalon. This is also the part of the brain that regulates other key functions such as temperature, thirst, fear and metabolism. A growing number of studies, however, suggest that the neocortex hosts other parts of the mechanics of the internal clock. The neocortex is the part of the brain that enable humans to connect thoughts and plan.

The Danish researchers therefore attempted to delete a gene in the mouse neocortex that is believed to regulate the circadian rhythm to see how this would affect the mice. Although this genetic change did not seem to affect their normal activities based on the circadian rhythm, the mice had more difficulty in resetting their internal clock when exposed to artificial changes equivalent to jet lag in humans.

Even more striking was the fact that the mice displayed depressive tendencies, including both more passive behaviour and a reduced amount of norepinephrine in the cerebral cortex: a stress hormone that is important for enabling the body’s fight-or-flight response.

The researchers believe that this newly discovered part of the human clock plays an important role in regulating our circadian rhythm and our mood. The new results are especially interesting because it has been recently shown that people with severe depression have similar changes in the genes in the same part of the brain that is associated with the internal clock. Improving understanding of and the potential for resetting this part of the internal clock may therefore be useful for treating depression.

The circadian oscillator of the cerebral cortex: molecular, biochemical and behavioral effects of deleting the Arntl clock gene in cortical neurons” has been published in Cerebral Cortex. In 2015, the Novo Nordisk Foundation awarded a grant to Martin Fredensborg Rath, Associate Professor at the Department of Neuroscience and Pharmacology of the University of Copenhagen, for the project Homeobox Genes in Development and Adult Function of the Mammalian Circadian Neuroendocrine System.