Autism spectrum disorder (ASD) is a diverse disorder that is likely to be caused by a combination of genetic alterations and environmental insult during early development. Studies demonstrate an association between maternal immune activation (MIA) during pregnancy and an increased risk for ASD. Recent development of mouse models for prenatal exposure to maternal immune activation (MIA) show that the challenged offspring demonstrate impaired behaviors relevant to ASD as well as exhibit altered levels of immune proteins. A significant gap exists in understanding how altered immune state interacts with ASD risk genes to result in impaired behaviors. Here we will test the hypothesis altered regulation of MHC1 proteins is a mechanism of convergence for MIA and ASD genetic risk factors. Specifically, we will examine how mutations in mecp2, a gene responsible for the Rett syndrome and also associated with non-Rett ASD cases, interact with MIA. We will, combine behavioral, molecular, electrophysiological and synaptic in vivo imaging analyses in relevant brain circuits to determine how altered Mecp2 levels and MIA converge to results in altered behavior and neuropathology.
Increasing evidence points to immunological dysfunction in autism spectrum disorders that may result from maternal infection. Here we will study how combined genetic and environmental risk factors result in behavioral and synaptic impairments and the underlying molecular mechanism.
|Bergdolt, Lara; Dunaevsky, Anna (2018) Brain changes in a maternal Immune activation model of neurodevelopmental brain disorders. Prog Neurobiol :|
|Pendyala, Gurudutt; Chou, Shinnyi; Jung, Yoosun et al. (2017) Maternal Immune Activation Causes Behavioral Impairments and Altered Cerebellar Cytokine and Synaptic Protein Expression. Neuropsychopharmacology 42:1435-1446|
|Coiro, Pierluca; Padmashri, Ragunathan; Suresh, Anand et al. (2015) Impaired synaptic development in a maternal immune activation mouse model of neurodevelopmental disorders. Brain Behav Immun 50:249-258|