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

被引:175
作者
Barca-Mayo, Olga [1 ,2 ]
Pons-Espinal, Meritxell [1 ]
Follert, Philipp [1 ]
Armirotti, Andrea [3 ]
Berdondini, Luca [2 ]
Tonelli, Davide De Pietri [1 ]
机构
[1] Fdn Ist Italiano Tecnol, Neurosci & Brain Technol Dept, Neurobiol miRNA Lab, Via Morego 30, I-16163 Genoa, Italy
[2] Fdn Ist Italiano Tecnol, Neurosci & Brain Technol Dept, Lab NetS3, Via Morego 30, I-16163 Genoa, Italy
[3] Fdn Ist Italiano Tecnol, PharmaChem D3, Dept Drug Discovery & Dev, Via Morego 30, I-16163 Genoa, Italy
关键词
RAT SUPRACHIASMATIC NUCLEUS; HIPPOCAMPUS-DEPENDENT MEMORY; TANDEM MASS-SPECTROMETRY; CORE CIRCADIAN CLOCK; LIQUID-CHROMATOGRAPHY; CEREBROSPINAL-FLUID; ACTIVITY RHYTHMS; SHORT-TERM; NEURONS; GLUTAMATE;
D O I
10.1038/ncomms14336
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:14
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