Effect of mPFC KLF4 on autism-like behaviors and possible mechanisms

Abstract Autism spectrum disorder (ASD) is a series of neurodevelopmental disorders with two core symptoms, repetitive behavioral phenotype, and social impairments, yet the underlying cellular and molecular mechanisms are still obscure. KLF4 (Kruppel-like factor 4) is a zinc finger protein transcription factor that has been widely reported in the regulation of cell proliferation, differentiation, survival, and apoptosis. Recently, increasing evidence demonstrated its critical role in neurodevelopment, microglia activating, and neuroinflammation in the central nervous system (CNS). Little is known about the effect of KLF4 in the medial prefrontal cortex (mPFC) on autism and autism-like behaviors. Here, we found that high and low expression levels of KLF4 in mPFC induced significant social novelty impairments. The molecular mechanisms might be associated with overexpression of KLF4 in mPFC promote activation of microglia and altered synaptic E/I ratio by affecting the expression of GluA1 and GABA-related proteins, the specific molecular mechanisms still need more investigations.