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

Jan 7, 2021Brain, behavior, and immunity

Changed daily body clock patterns in mice after immune activation during pregnancy linked to brain development disorders

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Poly I.C.-exposed male mouse offspring exhibited increased subjective day activity across different lighting conditions.

Prenatal maternal immune activation (MIA) was confirmed to elevate plasma levels of inflammatory markers in pregnant mice.
Adult male offspring exposed to MIA showed altered locomotor activity rhythms similar to those seen in neurodevelopmental disorders.
Increased activity was particularly noted at the start of the subjective day in 12:12 light/dark cycles and constant darkness, and at the end of the subjective day in 12:12 light/dark cycles.
Female offspring displayed much milder alterations in locomotor activity rhythms compared to male offspring after MIA exposure.
The behavioral impairments observed in adult offspring were not attributed to differences in maternal care.

AI simplified

Individuals with neurodevelopmental disorders, such as schizophrenia and autism spectrum disorder, exhibit various sleep and circadian rhythm disturbances that often persist and worsen throughout the lifespan. To study the interaction between circadian rhythm disruption and neurodevelopmental disorders, we utilized a mouse model based on prenatal maternal immune activation (MIA). We hypothesized that MIA exposure would lead to impaired circadian locomotor activity rhythms in adult mouse offspring. We induced MIA by injecting pregnant dams with polyinosinic:polycytidylic acid (poly IC) at embryonic day 9.5, then aged resulting offspring to adulthood. We first confirmed that poly IC injection in pregnant dams elevated plasma levels of pro- and anti-inflammatory cytokines and chemokines. We then placed adult offspring in running wheels and subjected them to various lighting conditions. Overall, poly IC-exposed male offspring exhibited altered locomotor activity rhythms, reminiscent of individuals with neurodevelopmental disorders. In particular, we report increased (subjective) day activity across 3 different lighting conditions: 12 h of light, 12 h of dark (12:12LD), constant darkness (DD) and constant light. Further data analysis indicated that this was driven by increased activity in the beginning of the (subjective) day in 12:12LD and DD, and at the end of the day in 12:12LD. This effect was sex-dependent, as in utero poly IC exposure led overall to much milder alterations in locomotor activity rhythms in female offspring than in male offspring. We also confirmed that the observed behavioral impairments in adult poly IC-exposed offspring were not due to differences in maternal behavior. These data further our understanding of the link between circadian rhythm disruption and neurodevelopmental disorders and may have implications for mitigating risk to the disorders and/or informing the development of circadian-based therapies.

Full Text

Full text is available at the source.

View full text (XML) ↗View full text ↗

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

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief