Summary: Light therapy activates the circadian rhythm associated Per1 gene in the lateral habenula, a brain area associated with mood regulation.

Source: PLOS

Light therapy can help improve the mood of people with seasonal affective disorder (SAD) during short winter days, but exactly how this therapy works is not well understood.

A new study by Urs Albrecht at the University of Fribourg, published July 8th in the journal PLOS Genetics, finds that light therapy’s beneficial effects come from activating the circadian clock gene Period1 in a part of the brain involved in mood and sleep-wake cycles.

Nighttime light has strong effects on the physiology and behavior of mammals. It can reset an animal’s circadian rhythms, and in the form of light therapy, affect mood in humans. Albrecht and his colleagues investigated how nighttime light impacts mood using mice as a model. They exposed mice to a pulse of light at different points during the night and then tested them for depressive behavior.

The researchers discovered that light exposure at the end of the dark period–two hours before daytime–had an antidepressant effect on the animals. The pulse of light activated the Period1 gene in a brain region called the lateral habenula, which plays a role in mood. Light at other times, however, had no effect. When they deleted the Period1 gene, the mice no longer experienced the light’s beneficial effects.

The new results provide evidence that turning on Period1 in the lateral habenula is the key to light’s mood-boosting powers. The discovery that mice appeared to be less depressed when exposed to light at the end of the dark period than the beginning is similar to findings in humans.

Per1 gene expression (yellow color) before (left panel) and after a 15 minute light pulse (right panel) given in the dark at zeitgeber time 22 in the lateral habenula (area visualized by hatched lines). The blue color depicts cell nuclei. The white line bottom left indicates the scale and corresponds to 200 μm. Credit: Iwona Olejniczak, 2021, PLOS Genetics

Light therapy is more efficient in the early morning than in the evening for patients with SAD. However, the researchers caution against making too many direct comparisons to humans since mice are nocturnal animals.

The researchers add, “Light perceived in the late part of the night induces expression of the clock gene Per1, which is related to improvement of depression like behavior in mice.”

Funding: This work was supported by the Velux Foundation (https://veluxstiftung.ch) Projects 995 and 772 to U.A. and the Swiss National Science Foundation (http://www.snf.ch) project number 310030_184667/1. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

About this depression research news

Source: PLOS
Contact: Urs Albrecht – PLOS
Image: The image is credited to Iwona Olejniczak, 2021, PLOS Genetics

Original Research: Open access.
“Light affects behavioral despair involving the clock gene Period 1” by Iwona Olejniczak et al. PLOS Genetics


Abstract

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Light affects behavioral despair involving the clock gene Period 1

Light at night has strong effects on physiology and behavior of mammals. It affects mood in humans, which is exploited as light therapy, and has been shown to reset the circadian clock in the suprachiasmatic nuclei (SCN). This resetting is paramount to align physiological and biochemical timing to the environmental light-dark cycle.

Here we provide evidence that light at zeitgeber time (ZT) 22 affects mood-related behaviors also in mice by activating the clock gene Period1 (Per1) in the lateral habenula (LHb), a brain region known to modulate mood-related behaviors.

We show that complete deletion of Per1 in mice led to depressive-like behavior and loss of the beneficial effects of light on this behavior. In contrast, specific deletion of Per1 in the region of the LHb did not affect mood-related behavior, but suppressed the beneficial effects of light. RNA sequence analysis in the mesolimbic dopaminergic system revealed profound changes of gene expression after a light pulse at ZT22.

In the nucleus accumbens (NAc), sensory perception of smell and G-protein coupled receptor signaling were affected the most. Interestingly, most of these genes were not affected in Per1 knock-out animals, indicating that induction of Per1 by light serves as a filter for light-mediated gene expression in the brain.

Taken together we show that light affects mood-related behavior in mice at least in part via induction of Per1 in the LHb with consequences on mood-related behavior and signaling mechanisms in the mesolimbic dopaminergic system.



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