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Modern lifestyles, e.g. transmeridian travel, night shift, light at night, etc., frequently disrupt people\u2019s regular sleep-wake cycles and create a misalignment (circadian desynchrony) between the natural environment and the endogenous body clock, and between different circadian oscillators within the body. The long-term consequences of circadian desynchrony on neurodevelopment and adult behavior remain elusive. Increasing clinical evidence supports a correlation between the disruption of the circadian system and neurodevelopmental disorders, such as autism spectrum disorders. Despite clinical correlations, experimental evidence is yet to establish a link between circadian disturbance in early life and adult behavioral changes. Here, using a \u201cshort day\u201d (SD) mouse model, in which mice were exposed to an 8\u2009h\/8\u2009h light\/dark (LD) cycle mimicking a \u201cshift work\u201d schedule from gestation day 1 to postnatal day 21, we performed a battery of behavioral tests to assess changes in adult behaviors, including sociability, affective behaviors, stereotypy, cognition and locomotor functions. In contrast to the control mice kept in a 12\u2009h\/12\u2009h LD cycle, the adult SD mice entrained to the 8\u2009h\/8\u2009h LD cycle, but their free running rhythms remained normal in constant darkness. Interestingly, however, the SD mice displayed diminished sociability, a reduced preference for social novelty, excessive repetitive behaviors, and compromised cognitive functions, all of which resemble characteristics of autism-like behavioral alterations. In addition, the SD mice exhibited significant anxiety- and depressive-like behaviors and impaired motor functions. By western blotting and immunostaining analyses, hyperactivation of the mTORC1\/S6K1 pathway was detected in multiple forebrain regions of SD mice. These findings underscore the enduring impact of early-life circadian disruption on neurochemical signaling and behavioral patterns into adulthood, highlighting a pivotal role for circadian regulation in neurodevelopment.<\/jats:p>","DOI":"10.1038\/s42003-024-07131-3","type":"journal-article","created":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T10:08:50Z","timestamp":1731319730000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Circadian desynchrony in early life leads to enduring autistic-like behavioral changes in adulthood"],"prefix":"10.1038","volume":"7","author":[{"given":"Abhishek","family":"Mishra","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rubal","family":"Singla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nam","family":"Le","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2408-4697","authenticated-orcid":false,"given":"Michael","family":"Oraebosi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8941-0812","authenticated-orcid":false,"given":"Dong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5105-7726","authenticated-orcid":false,"given":"Ruifeng","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,11]]},"reference":[{"key":"7131_CR1","doi-asserted-by":"publisher","first-page":"e62","DOI":"10.1371\/journal.pbio.1000062","volume":"7","author":"M Rosbash","year":"2009","unstructured":"Rosbash, M. 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