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Disruption of circadian rhythms by ambient light during neu-rodevelopment leads to autistic-like molecular and behavioral alterations in adult mice

ABSTRACT: Disruption of circadian rhythms by ambient light during neu-rodevelopment leads to autistic-like molecular and behavioral alterations in adult mice

PROVIDER: PRJNA782353 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR16995541.fastq.gz	Fastqsanger.gz
	SRR16995542.fastq.gz	Fastqsanger.gz
	SRR16995543.fastq.gz	Fastqsanger.gz
	SRR16995544.fastq.gz	Fastqsanger.gz
	SRR16995545.fastq.gz	Fastqsanger.gz

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Disruption of circadian rhythms by ambient light during neu-rodevelopment leads to autistic-like molecular and behavioral alterations in adult mice

Project description:Although circadian rhythms are thought to be essential for maintaining body health, the effects of chronic circadian disruption during neurodevelopment remain elusive. Here, using the “Short Day” (SD) mouse model, in which an 8h/8h Light/Dark (LD) cycle was applied during E1-P42, we investigated molecular and behavioral changes after circadian disruption in mice. Adult SD mice fully entrained to the 8h/8h LD cycle and their circadian oscillations of clock protein PERI-OD1 and PERIOD2 were disrupted in the suprachiasmatic nucleus and the hippocampus. RNA-seq revealed changes in the transcriptome associated with neurodevelopment, translational control, and autism. Western blotting and immunostaining identified hyperactivation of the mTOR and MAPK signaling and enhanced global protein synthesis in the hippocampus of SD mice. Electrophysiological recording uncovered enhanced excitatory but attenuated inhibitory synaptic transmission in the hippocampal CA1 pyramidal neurons. These functional changes are corroborated by immature dendritic spine morphology in these neurons. Lastly, autistic-like be-havioral changes, including impaired social interaction and communication, increased repetitive behaviors and impaired novel object recognition and location memory, were found in SD mice. Together, these findings demonstrate autistic-like phenotypes in SD mice and highlight a critical role for circadian rhythm in neurodevelopment.

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Disruption of Circadian Rhythms by Ambient Light during Neurodevelopment Leads to Autistic-like Molecular and Behavioral Alterations in Adult Mice.

Project description:Although circadian rhythms are thought to be essential for maintaining body health, the effects of chronic circadian disruption during neurodevelopment remain elusive. Here, using the "Short Day" (SD) mouse model, in which an 8 h/8 h light/dark (LD) cycle was applied from embryonic day 1 to postnatal day 42, we investigated the molecular and behavioral changes after circadian disruption in mice. Adult SD mice fully entrained to the 8 h/8 h LD cycle, and the circadian oscillations of the clock proteins, PERIOD1 and PERIOD2, were disrupted in the suprachiasmatic nucleus and the hippocampus of these mice. By RNA-seq widespread changes were identified in the hippocampal transcriptome, which are functionally associated with neurodevelopment, translational control, and autism. By western blotting and immunostaining hyperactivation of the mTOR and MAPK signaling pathways and enhanced global protein synthesis were found in the hippocampi of SD mice. Electrophysiological recording uncovered enhanced excitatory, but attenuated inhibitory, synaptic transmission in the hippocampal CA1 pyramidal neurons. These functional changes at synapses were corroborated by the immature morphology of the dendritic spines in these neurons. Lastly, autistic-like animal behavioral changes, including impaired social interaction and communication, increased repetitive behaviors, and impaired novel object recognition and location memory, were found in SD mice. Together, these results demonstrate molecular, cellular, and behavioral changes in SD mice, all of which resemble autistic-like phenotypes caused by circadian rhythm disruption. The findings highlight a critical role for circadian rhythms in neurodevelopment.

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