The Circadian Oscillator of the Cerebral Cortex: Molecular, Biochemical and Behavioral Effects of Deleting the<i>Arntl</i>Clock Gene in Cortical Neurons

Bering, Tenna; Carstensen, Mikkel B.; Wörtwein, Gitta; Weikop, Pia; Rath, Martin F.

doi:10.1093/cercor/bhw406

Cited by 24 publications

(40 citation statements)

References 57 publications

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“…; Bering et al . ), but we here present the first model with a neuronal cell‐specific clock gene deletion outside the forebrain. Our data provide evidence that Arntl is essential for the molecular clockwork of the cerebellar cortex; however, although the cerebellum plays a central role in motor control, deletion of Arntl does not influence circadian locomotor activity.…”

Section: Discussionmentioning

confidence: 99%

“…Notably, the cerebral cortices in these control mice have been used in a previous study (Bering et al . ).…”

Section: Methodsmentioning

confidence: 97%

“…During the same experimental session, brains for a study on the cerebral cortex were obtained (Bering et al . ). Coronal cryostat sections (12 μm) were hybridized with [ 35 S]dATP‐labeled antisense DNA probes (Klitten et al .…”

Section: Methodsmentioning

confidence: 97%

“…During the same experimental session, brains for a study on the cerebral cortex were obtained (Bering et al . ).…”

Section: Methodsmentioning

confidence: 97%

“…, ) and clock gene expression in a conditional Arntl knockout model (Bering et al . ), where this design has proven to be sufficient for detecting both circadian rhythms and differences between genotypes in expression patterns in 90% of the clock genes analyzed. We expected the biological variation and differences between genotypes, that is the effect size, to be of similar magnitude in the current study.…”

Section: Methodsmentioning

confidence: 99%

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Deleting the Arntl clock gene in the granular layer of the mouse cerebellum: impact on the molecular circadian clockwork

Bering

Carstensen

Rath

2017

Journal of Neurochemistry

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The suprachiasmatic nucleus houses the central circadian clock and is characterized by the timely regulated expression of clock genes. However, neurons of the cerebellar cortex also contain a circadian oscillator with circadian expression of clock genes being controlled by the suprachiasmatic nucleus. It has been suggested that the cerebellar circadian oscillator is involved in food anticipation, but direct molecular evidence of the role of the circadian oscillator of the cerebellar cortex is currently unavailable. To investigate the hypothesis that the circadian oscillator of the cerebellum is involved in circadian physiology and food anticipation, we therefore by use of Cre-LoxP technology generated a conditional knockout mouse with the core clock gene Arntl deleted specifically in granule cells of the cerebellum, since expression of clock genes in the cerebellar cortex is mainly located in this cell type. We here report that deletion of Arntl heavily influences the molecular clock of the cerebellar cortex with significantly altered and arrhythmic expression of other central clock and clock-controlled genes. On the other hand, daily expression of clock genes in the suprachiasmatic nucleus was unaffected. Telemetric registrations in different light regimes did not detect significant differences in circadian rhythms of running activity and body temperature between Arntl conditional knockout mice and controls. Furthermore, food anticipatory behavior did not differ between genotypes. These data suggest that Arntl is an essential part of the cerebellar oscillator; however, the oscillator of the granular layer of the cerebellar cortex does not control traditional circadian parameters or food anticipation.

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Section: Discussionmentioning

confidence: 99%

“…Notably, the cerebral cortices in these control mice have been used in a previous study (Bering et al . ).…”

Section: Methodsmentioning

confidence: 97%

Section: Methodsmentioning

confidence: 97%

“…During the same experimental session, brains for a study on the cerebral cortex were obtained (Bering et al . ).…”

Section: Methodsmentioning

confidence: 97%

Section: Methodsmentioning

confidence: 99%

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Deleting the Arntl clock gene in the granular layer of the mouse cerebellum: impact on the molecular circadian clockwork

Bering

Carstensen

Rath

2017

Journal of Neurochemistry

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Diurnal proteome profile of the mouse cerebral cortex: Conditional deletion of the Bmal1 circadian clock gene elevates astrocyte protein levels and cell abundance in the neocortex and hippocampus

Bering

Gadgaard

Vorum

et al. 2023

Glia

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Circadian oscillators, defined by cellular 24 h clock gene rhythms, are found throughout the brain. Cerebral cortex‐specific conditional knockout of the clock gene Bmal1 (Bmal1 CKO) leads to depressive‐like behavior, but the molecular link from clock gene to altered behavior is unknown. Further, diurnal proteomic data on the cerebral cortex are currently unavailable. With the aim of determining the diurnal proteome profile and downstream targets of the cortical circadian clock, we here performed a proteomic analysis of the mouse cerebral cortex. Proteomics identified approximately 2700 proteins in both the neocortex and the hippocampus. In the neocortex, 15 proteins were differentially expressed (>2‐fold) between day and night, mainly mitochondrial and neuronal plasticity proteins. Only three hippocampal proteins were differentially expressed, suggesting that daily protein oscillations are more prominent in the neocortex. The number of differentially expressed proteins was reduced in the Bmal1 CKO, suggesting that daily rhythms in the cerebral cortex are primarily driven by local clocks. The proteome of the Bmal1 CKO cerebral cortex was dominated by upregulated proteins expressed in astrocytes, including GFAP (4‐fold) and FABP7 (>20‐fold), in both the neocortex and hippocampus. These findings were confirmed at the transcript level. Cellular analyses of astrocyte components revealed an increased number of GFAP‐positive cells in the Bmal1 CKO cerebral cortex. Further, BMAL1 was found to be expressed in both GFAP‐ and FABP7‐positive astrocytes of control animals. Our data show that Bmal1 is required for proper cellular composition of the cerebral cortex, suggesting that increased cortical astrocyte activity may induce behavioral changes.

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The Role of the Circadian System in Attention Deficit Hyperactivity Disorder

Bondopadhyay

Díaz-Orueta

Coogan

2021

Advances in Experimental Medicine and Biology

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The Circadian Oscillator of the Cerebral Cortex: Molecular, Biochemical and Behavioral Effects of Deleting theArntlClock Gene in Cortical Neurons

Cited by 24 publications

References 57 publications

Deleting the Arntl clock gene in the granular layer of the mouse cerebellum: impact on the molecular circadian clockwork

Deleting the Arntl clock gene in the granular layer of the mouse cerebellum: impact on the molecular circadian clockwork

Diurnal proteome profile of the mouse cerebral cortex: Conditional deletion of the Bmal1 circadian clock gene elevates astrocyte protein levels and cell abundance in the neocortex and hippocampus

The Role of the Circadian System in Attention Deficit Hyperactivity Disorder

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