The Effects Of Hippocampal Astrocyte Activation During Developmental Period On Autism Like Behaviors In Mice

Autism spectrum disorders(ASD)are a neurodevelopmental disorders with high heritability,but complex acquired factors are also associated with the high prevalence of autism,suggesting the crucial interplay of genetic and environmental factors in ASD pathogenesis in the growing brain.It has been hypothesized that autism may result from an imbalance between excitatory and inhibitory neural circuits.Astrocytes regulate neuron development,playing a crucial role in synaptic tuning and neuronal wiring in late prenatal and early postnatal days.Abnormal astrocyte development can lead to many serious neurodevelopmental disorders including ASD.These lines of evidence indicate that astrocytes may participate in ASD pathogenesis through regulation function of excitatory glutamatergic system and/or inhibitory GABAergic system during development.However,the current understanding of the association among astrocyte activation,excitatory glutamatergic system and inhibitory GABAergic system in ASD pathogenesis is still limited.In this study,we will explore the effects of astrocytic activation in hippocampus during developmental period on autism like behaviors in mice,as well as the possibly underlying mechanisms.Here we report that extra astrocyte activation in hippocampus by in utero electroporating epidermal growth factor receptor(EGFR)plasmid in mice at embryonic day 15(E15)significantly increases autism-like behaviors,including grooming and social tests,decreasesexcitatory synapse development and increases GAD67-positive neurons in hippocampus.These results suggest that abnormal activation of hippocampal astrocytes during developmental period in mice are involved in ASD pathogenesis,leading from an imbalance between excitatory glutamatergic and inhibitory GABAergic pathways.