Impaired synaptic development in a maternal immune activation mouse model of neurodevelopmental disorders

Authors

Pierluca Coiro, University of Nebraska Medical Center, OmahaFollow
Ragunathan Padmashri, University of Nebraska Medical Center, OmahaFollow
Anand Suresh, University of Nebraska Medical Center, Omaha
Elizabeth Spartz, University of Nebraska Medical Center, Omaha
Gurudutt Pendyala, University of Nebraska Medical Center, OmahaFollow
Shinnyi Chou, University of Nebraska Medical Center, Omaha
Yoosun Jung, University of Nebraska Medical Center, OmahaFollow
Brittney Meays, University of Nebraska Medical Center, OmahaFollow
Shreya Roy, University of Nebraska Medical Center, Omaha
Nagsen Gautam, University of Nebraska Medical Center, OmahaFollow
Yazen Alnouti, University of Nebraska Medical Center, OmahaFollow
Ming Li, University of Nebraska-LincolnFollow
Anna Dunaevsky, University of Nebraska Medical Center, OmahaFollow

Document Type

Article

Date of this Version

7-2015

Citation

Published in Brain, Behavior, and Immunity 50 (2015), pp. 249–258; doi: 10.1016/j.bbi.2015.07.022

Comments

Copyright © 2015 Elsevier Inc. Used by permission.

Abstract

Both genetic and environmental factors are thought to contribute to neurodevelopmental and neuropsychiatric disorders with maternal immune activation (MIA) being a risk factor for both autism spectrum disorders and schizophrenia. Although MIA mouse offspring exhibit behavioral impairments, the synaptic alterations in vivo that mediate these behaviors are not known. Here we employed in vivo multiphoton imaging to determine that in the cortex of young MIA offspring there is a reduction in number and turnover rates of dendritic spines, sites of majority of excitatory synaptic inputs. Significantly, spine impairments persisted into adulthood and correlated with increased repetitive behavior, an ASD relevant behavioral phenotype. Structural analysis of synaptic inputs revealed a reorganization of presynaptic inputs with a larger proportion of spines being contacted by both excitatory and inhibitory presynaptic terminals. These structural impairments were accompanied by altered excitatory and inhibitory synaptic transmission. Finally, we report that a postnatal treatment of MIA offspring with the anti-inflammatory drug ibudilast, prevented both synaptic and behavioral impairments. Our results suggest that a possible altered inflammatory state associated with maternal immune activation results in impaired synaptic development that persists into adulthood but which can be prevented with early anti-inflammatory treatment.

Includes supplementary materials.