Altered circadian rhythms in a mouse model of neurodevelopmental disorders based on prenatal maternal immune activation |
| |
| Institution: | 1. Departamento de Farmacologia, Universidade Federal de São Paulo, R. Botucatu, 862, Ed. Leal Prado, 1° andar, 04023062 São Paulo, SP, Brazil;2. Departamento de Psicobiologia, Universidade Federal de São Paulo, R. Napoleão de Barros, 925, 04021002 São Paulo, SP, Brazil;1. Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan;2. Department of Cell Biology and Neuroscience, Juntendo University Graduate School of Medicine, Tokyo, Japan;3. Center for Information and Neural Networks, National Institute of Information and Communications Technology, Suita City, Osaka, Japan |
| |
| Abstract: | 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. |
| |
| Keywords: | Circadian rhythms Neurodevelopmental risk factor Schizophrenia Autism spectrum disorder Interaction Disrupted activity rhythms Prenatal immune challenge Poly IC Wheel running Mouse model |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
