Altered circadian rhythms in a mouse model of neurodevelopmental disorders based on prenatal maternal immune activation

Delorme, Tara C.; Srivastava, Lalit K.; Cermakian, Nicolas

doi:10.1016/j.bbi.2020.12.030

Cited by 14 publications

(19 citation statements)

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“…Indeed, patients with schizophrenia display reduced total sleep time, reduced sleep quality and reduced slow-wave sleep ( Hofstetter et al, 2005 ; van Kammen et al, 1988 ). Using mouse models to study schizophrenia, multiple reports have also shown abnormal circadian phenotypes, such as decreased dark phase activity and increased daytime activity ( Bhardwaj et al, 2015 ; Delorme et al, 2020 , 2021 ; Ingiosi et al, 2019 ; Lee et al, 2018 ).…”

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confidence: 99%

Exposure to Circadian Disruption During Adolescence Interacts With a Genetic Risk Factor to Modify Schizophrenia-relevant Behaviors in a Sex-dependent Manner

2022

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DTNBP1 is a gene associated with schizophrenia. Postmortem studies found a reduced expression of DTNBP1 in regions associated with schizophrenia in patients’ brains. Sandy (Sdy) mice have a loss-of-function mutation in Dtnbp1 gene, 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 chronic jetlag (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 with Dtnbp1 mutation, can influence cognition, sociability, sensorimotor gating, and anxiety-like behaviors in a sex-dependent manner.

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confidence: 99%

Exposure to Circadian Disruption During Adolescence Interacts With a Genetic Risk Factor to Modify Schizophrenia-relevant Behaviors in a Sex-dependent Manner

2022

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“…Early life events are known to greatly influence brain development, and HPA activity. A series of animal studies have suggested environmental factors, such as valproic acid (VPA), maternal immune activation, and maternal separation, resulted in the systemic stress reaction and autism-like behaviors (36)(37)(38). As we all know, chronic stress primarily promotes the release of excessive cortisol from the adrenal gland, which tends to activate microglia.…”

Section: Discussionmentioning

confidence: 99%

Alteration of peripheral cortisol and autism spectrum disorder: A meta-analysis

et al. 2022

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Cortisol is the main HPA axis hormone secreted by the adrenal cortex, and influences metabolism, cognition, and behavior. Recently, a plethora of studies have tried to confirm the correlation between peripheral cortisol and autism spectrum disorder (ASD). However, the results were controversial. We assessed the effects of peripheral cortisol on ASD in this study. The included studies were identified according to the inclusion and exclusion criteria. The pooled Hedges’ g and its 95% confidence interval were selected to evaluate the association between peripheral cortisol and ASD. Subgroup analyses, sensitivity analyses, meta-regression, and publication bias tests were also undertaken based on the obtained information. There were a total of twelve studies with 375 ASD patients and 335 controls included in our meta-analysis. Obvious heterogeneity across studies was found in the overall analysis. Peripheral cortisol levels were significantly elevated in ASD patients compared with controls in the absence of obvious heterogeneity. A single study did not influence the overall comparison results. Meta-regression analyses revealed that age and gender of the included subjects, sample size, and publication year did not moderate effects on the present results. These findings may provide us some targeted strategies to the diagnosis and treatment of ASD.

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“…After the 2-week acclimatization period in LD, post-light disruption, wheel running activity analysis was performed as previously described ( Brown et al, 2019 ; Delorme et al, 2021 ). Briefly, mice were individually housed in running wheel cages, which were placed in light-proof ventilated cabinets.…”

Section: Methodsmentioning

confidence: 99%

Chronic Exposure to Dim Light at Night or Irregular Lighting Conditions Impact Circadian Behavior, Motor Coordination, and Neuronal Morphology

et al. 2022

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Mistimed exposure to light has been demonstrated to negatively affect multiple aspects of physiology and behavior. Here we analyzed the effects of chronic exposure to abnormal lighting conditions in mice. We exposed mice for 1 year to either: a standard light/dark cycle, a “light-pollution” condition in which low levels of light were present in the dark phase of the circadian cycle (dim light at night, DLAN), or altered light cycles in which the length of the weekday and weekend light phase differed by 6 h (“social jetlag”). Mice exhibited several circadian activity phenotypes, as well as changes in motor function, associated particularly with the DLAN condition. Our data suggest that these phenotypes might be due to changes outside the core clock. Dendritic spine changes in other brain regions raise the possibility that these phenotypes are mediated by changes in neuronal coordination outside of the clock. Given the prevalence of artificial light exposure in the modern world, further work is required to establish whether these negative effects are observed in humans as well.

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Altered circadian rhythms in a mouse model of neurodevelopmental disorders based on prenatal maternal immune activation

Cited by 14 publications

References 70 publications

Exposure to Circadian Disruption During Adolescence Interacts With a Genetic Risk Factor to Modify Schizophrenia-relevant Behaviors in a Sex-dependent Manner

Exposure to Circadian Disruption During Adolescence Interacts With a Genetic Risk Factor to Modify Schizophrenia-relevant Behaviors in a Sex-dependent Manner

Alteration of peripheral cortisol and autism spectrum disorder: A meta-analysis

Chronic Exposure to Dim Light at Night or Irregular Lighting Conditions Impact Circadian Behavior, Motor Coordination, and Neuronal Morphology

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