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

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 postnata...

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Autores principales: Fang, Kun, Liu, Dong, Pathak, Salil S., Yang, Bowen, Li, Jin, Karthikeyan, Ramanujam, Chao, Owen Y., Yang, Yi-Mei, Jin, Victor X., Cao, Ruifeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699695/
https://www.ncbi.nlm.nih.gov/pubmed/34943821
http://dx.doi.org/10.3390/cells10123314
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author Fang, Kun
Liu, Dong
Pathak, Salil S.
Yang, Bowen
Li, Jin
Karthikeyan, Ramanujam
Chao, Owen Y.
Yang, Yi-Mei
Jin, Victor X.
Cao, Ruifeng
author_facet Fang, Kun
Liu, Dong
Pathak, Salil S.
Yang, Bowen
Li, Jin
Karthikeyan, Ramanujam
Chao, Owen Y.
Yang, Yi-Mei
Jin, Victor X.
Cao, Ruifeng
author_sort Fang, Kun
collection PubMed
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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spelling pubmed-86996952021-12-24 Disruption of Circadian Rhythms by Ambient Light during Neurodevelopment Leads to Autistic-like Molecular and Behavioral Alterations in Adult Mice Fang, Kun Liu, Dong Pathak, Salil S. Yang, Bowen Li, Jin Karthikeyan, Ramanujam Chao, Owen Y. Yang, Yi-Mei Jin, Victor X. Cao, Ruifeng Cells Article 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. MDPI 2021-11-26 /pmc/articles/PMC8699695/ /pubmed/34943821 http://dx.doi.org/10.3390/cells10123314 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fang, Kun
Liu, Dong
Pathak, Salil S.
Yang, Bowen
Li, Jin
Karthikeyan, Ramanujam
Chao, Owen Y.
Yang, Yi-Mei
Jin, Victor X.
Cao, Ruifeng
Disruption of Circadian Rhythms by Ambient Light during Neurodevelopment Leads to Autistic-like Molecular and Behavioral Alterations in Adult Mice
title Disruption of Circadian Rhythms by Ambient Light during Neurodevelopment Leads to Autistic-like Molecular and Behavioral Alterations in Adult Mice
title_full Disruption of Circadian Rhythms by Ambient Light during Neurodevelopment Leads to Autistic-like Molecular and Behavioral Alterations in Adult Mice
title_fullStr Disruption of Circadian Rhythms by Ambient Light during Neurodevelopment Leads to Autistic-like Molecular and Behavioral Alterations in Adult Mice
title_full_unstemmed Disruption of Circadian Rhythms by Ambient Light during Neurodevelopment Leads to Autistic-like Molecular and Behavioral Alterations in Adult Mice
title_short Disruption of Circadian Rhythms by Ambient Light during Neurodevelopment Leads to Autistic-like Molecular and Behavioral Alterations in Adult Mice
title_sort disruption of circadian rhythms by ambient light during neurodevelopment leads to autistic-like molecular and behavioral alterations in adult mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699695/
https://www.ncbi.nlm.nih.gov/pubmed/34943821
http://dx.doi.org/10.3390/cells10123314
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