Astrocyte deletion of Bmal1 alters daily locomotor activity and cognitive functions via GABA signalling

作者：Barca Mayo Olga; Pons Espinal Meritxell; Follert Philipp; Armirotti Andrea; Berdondini Luca; Tonelli Davide De Pietri

来源：Nature Communications, 2017, 8(1): 14336.

DOI：10.1038/ncomms14336

<jats:title>Abstract</jats:title><jats:p>Circadian rhythms are controlled by a network of clock neurons in the central pacemaker, the suprachiasmatic nucleus (SCN). Core clock genes, such as <jats:italic>Bmal1</jats:italic>, are expressed in SCN neurons and in other brain cells, such as astrocytes. However, the role of astrocytic clock genes in controlling rhythmic behaviour is unknown. Here we show that ablation of <jats:italic>Bmal1</jats:italic> in GLAST-positive astrocytes alters circadian locomotor behaviour and cognition in mice. Specifically, deletion of astrocytic <jats:italic>Bmal1</jats:italic> has an impact on the neuronal clock through GABA signalling. Importantly, pharmacological modulation of GABAA-receptor signalling completely rescues the behavioural phenotypes. Our results reveal a crucial role of astrocytic <jats:italic>Bmal1</jats:italic> for the coordination of neuronal clocks and propose a new cellular target, astrocytes, for neuropharmacology of transient or chronic perturbation of circadian rhythms, where alteration of astrocytic clock genes might contribute to the impairment of the neurobehavioural outputs such as cognition.</jats:p>

• 出版日期2017-2-10