Deletion of the Clock GenePeriod2 (Per2)in Glial Cells Alters Mood-Related Behavior in Mice

Abstract

The circadian clock regulates many biochemical and physiological pathways, and lack of clock genes, such as Period (Per) 2, do not only affect circadian activity rhythms, but can also modulate food-anticipatory and mood-related behaviors. However, it is not known how cell-type specific expression of Per2 contributes to these behaviors. In this study, we find that Per2 in glial cells is important for balancing mood-related behaviors. Genetic and adeno-associated virus-mediated deletion of Per2 in glial cells of mice leads to a depression-resistant phenotype, as manifested in reduced despair and anxiety. This is paralleled by an increase of the GABA transporter 3 (Gat3) mRNA and a reduction of glutamate levels in the nucleus accumbens (NAc). Exclusive deletion of Per2 in glia of the NAc reduced despair, but had no influence on anxiety. Our data provide strong evidence for an important role of glial Per2 in regulating mood-related behavior.

Emotionally clocked out: cell-type specific regulation of mood and anxiety by the circadian clock system in the brain

“…However, neuronal Per2 knockout also reduces despair, but not anxiety responses. Astrocytic Bmal1 deletion in the NAc did not affect despair or anxiety (Martini et al, 2021). A recent study demonstrated that astrocytes in the NAc showed strong molecular rhythms which regulates NAc metabolic homeostasis and behavior.…”

“…Importantly, astrocytes also contain a circadian molecular clock and clock genes regulate astrocyte functions (Prolo et al, 2005;Brancaccio et al, 2017). Deletion of Per2 in mouse astrocytes reduced despair and anxiety associated with increased GABA transporter 2 and dopamine receptor D3 mRNA and reduced glutamate levels in the NAc (Martini et al, 2021). However, neuronal Per2 knockout also reduces despair, but not anxiety responses.…”