Exposure to Environmental Factors rescues spine defects of Eps8 KO mice

Abstract

Several neuropsychiatric diseases, including autism spectrum disorders (ASD) and intellectual disability (ID) are characterized by synaptic dysfunctions, such as, altered number and shape of dendritic spines, and defective synaptic signalling and plasticity. The actin regulatory protein, Eps8, plays a key role in spine morphogenesis and plasticity since neurons lacking Eps8 show defective spine morphology and density and fail to undergo long term potentiation. Consistently, Eps8 KO mice display increased density of immature spines in CA1 hippocampal region and cognitive defects. Also, lower levels of Eps8 have been detected in the brain of a cohort of ASD patients. Preclinical studies showed that environmental factors, such as mice exposure to environmental enrichment (EE) or neuron exposure to increased extracellular Mg2+, may have a “plasticizing action” resulting in improved cognitive functions and higher cellular plasticity. Here, we tested whether early EE or high Mg2+ exposure may rescue the structural synaptic defects of Eps8 KO mice and neurons. Results of this study indicate that the early EE treatment in mice and elevated extracellular Mg2+ concentration in neurons restore normal dendritic morphology and synaptic plasticity in Eps8 KO mice and neurons. These data suggest that early “plasticizing” interventions can be beneficial on synaptic defects and their efficacy in the treatment of neuro-developmental diseases is worth to be investigated.