title: Astrocyte deletion of Bmal1 alters daily locomotor activity and cognitive functions via GABA signalling.
abstract: Circadian rhythms are controlled by a network of clock neurons in the central pacemaker, the suprachiasmatic nucleus (SCN). Core clock genes, such as Bmal1, 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 Bmal1 in GLAST-positive astrocytes alters circadian locomotor behaviour and cognition in mice. Specifically, deletion of astrocytic Bmal1 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 Bmal1 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.
authors.affiliation: Neurobiology of miRNA Lab, Neuroscience and Brain Technologies Department, Fondazione Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genoa, Italy.|NetS3 Lab, Neuroscience and Brain Technologies Department, Fondazione Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genoa, Italy.
authors.forename: Olga
authors.initials: O
authors.lastname: Barca-Mayo
authors.affiliation: Neurobiology of miRNA Lab, Neuroscience and Brain Technologies Department, Fondazione Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genoa, Italy.
authors.forename: Meritxell
authors.initials: M
authors.lastname: Pons-Espinal
authors.affiliation: Neurobiology of miRNA Lab, Neuroscience and Brain Technologies Department, Fondazione Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genoa, Italy.
authors.forename: Philipp
authors.initials: P
authors.lastname: Follert
authors.affiliation: D3 PharmaChemistry, Department of Drug Discovery and Development, Fondazione Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genoa, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Armirotti
authors.affiliation: NetS3 Lab, Neuroscience and Brain Technologies Department, Fondazione Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genoa, Italy.
authors.forename: Luca
authors.identifier: 0000-0001-9521-2812
authors.initials: L
authors.lastname: Berdondini
authors.affiliation: Neurobiology of miRNA Lab, Neuroscience and Brain Technologies Department, Fondazione Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genoa, Italy.
authors.forename: Davide
authors.identifier: 0000-0001-9537-8900
authors.initials: D
authors.lastname: De Pietri Tonelli
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D057906:Circadian Clocks / Q000235:genetics / Q000502:physiology; D003071:Cognition / Q000502:physiology*; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D017384:Sequence Deletion; D015398:Signal Transduction; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse; D005680:gamma-Aminobutyric Acid