Circadian disruption during adolescence may influence behaviors related to cognition and sociability in a sex-dependent manner.
Behavioral assessments indicated that had opposing effects on wild-type and Sdy male mice, causing deficits in wild-type while improving preexisting deficits in Sdy mice.
Both wild-type and Sdy mice exhibited decreased sociability due to chronic jetlag.
Chronic jetlag resulted in decreased sensorimotor gating as measured by prepulse inhibition, specifically in female mice.
Sdy mice displayed reduced anxiety-like behavior compared to wild-type mice, with chronic jetlag further increasing this effect in males.
Simplified
is a gene associated with schizophrenia. Postmortem studies found a reduced expression ofin regions associated with schizophrenia in patients' brains. Sandy (Sdy) mice have a loss-of-function mutation ingene, resulting in behavioral deficits and brain changes similar to those seen in patients with schizophrenia. We previously showed that exposing adult Sdy mice to circadian disruption led to an exacerbation of schizophrenia-relevant behaviors. Here we asked whether the interaction between this genetic risk factor and circadian disruption occurs during adolescence, a period when environmental insults can promote schizophrenia symptoms, and whether sex affects this interaction. Starting at postnatal day 21, wild-type (WT) and Sdy males and females were housed for 4 weeks either in a 12 h light:12 h dark (LD 12:12) cycle or under (CJL). Then, after 2 weeks in LD 12:12, behavioral assessments were conducted, including elevated plus maze (EPM), novel object recognition (NOR), social interaction, and prepulse inhibition (PPI) of acoustic startle. NOR and social novelty tests showed that, surprisingly, CJL during adolescence had opposite effects on WT and Sdy males, that is, behavioral deficits in WT males while rescuing preexisting deficits in Sdy mice. CJL led to decreased sociability in WT and Sdy mice while decreasing PPI only in females. Sdy mice showed decreased anxiety-like behavior compared with wild-type (WT), which was further accentuated by CJL in males. Thus, circadian disruption during adolescence, on its own or in association withmutation, can influence cognition, sociability, sensorimotor gating, and anxiety-like behaviors in a sex-dependent manner. DTNBP1DTNBP1Dtnbp1Dtnbp1
Key numbers
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Decrease in Sociability
WT males spent less time with a novel conspecific compared to controls.
2.558
Recognition Memory Improvement
Sdy males demonstrated proper recognition of the novel object after .
0.0001
Reduced Sensorimotor Gating
led to decreased percentage PPI in female mice compared to controls.
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