Beschreibung:
<jats:title>Abstract</jats:title><jats:p>The circadian clock regulates many biochemical and physiological pathways, and lack of clock genes, such as <jats:italic>Period</jats:italic> (<jats:italic>Per</jats:italic>) 2, affects not only circadian activity rhythms, but can also modulate feeding and mood-related behaviors. However, it is not known how cell-type specific expression of <jats:italic>Per2</jats:italic> contributes to these behaviors. In this study, we find that <jats:italic>Per2</jats:italic> in glial cells is important for balancing mood-related behaviors, without affecting circadian activity parameters. Genetic and adeno-associated virus-mediated deletion of <jats:italic>Per2</jats:italic> in glial cells of mice leads to reduced despair and anxiety. This is paralleled by an increase of the <jats:italic>GABA transporter 2</jats:italic> (<jats:italic>Gat2/Slc6a13</jats:italic>) and <jats:italic>Dopamine receptor D3</jats:italic> (<jats:italic>Drd3</jats:italic>) mRNA, and a reduction of glutamate levels in the nucleus accumbens (NAc). Interestingly, neuronal <jats:italic>Per2</jats:italic> knock-out also reduces despair, but does not influence anxiety. The change in mood-related behavior is not a result of a defective molecular clock, as glial <jats:italic>Bmal1</jats:italic> deletion has no effect on neither despair nor anxiety. Exclusive deletion of <jats:italic>Per2</jats:italic> in glia of the NAc reduced despair, but had no influence on anxiety. Our data provide strong evidence for an important role of glial <jats:italic>Per2</jats:italic> in regulating mood-related behavior.</jats:p>