Striatal synaptic changes and behavior in adult mouse upon prenatal exposure to valproic acid.

Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders characterized by persistent deficits in social communication and social interaction. Altered synaptogenesis and aberrant connectivity responsible for social behavior and communication have been reported in autism pathogenesis. Autism has a strong genetic and heritable component; however, environmental factors including toxins, pesticides, infection and in utero exposure to drugs such as VPA have also been implicated in ASD. Administration of VPA during pregnancy has been used as a rodent model to study pathophysiological mechanisms involved in ASD, and in this study, we used the mouse model of prenatal exposure to VPA to assess the effects on striatal and dorsal hippocampus function in adult mice. Alterations in repetitive behaviors and shift habits were observed in mice prenatally exposed to VPA. In particular, such mice presented a better performance in learned motor skills and cognitive deficits in Y-maze learning frequently associated with striatal and hippocampal function. These behavioral changes were associated with a decreased level of proteins involved in the formation and maintenance of excitatory synapses, such as Nlgn-1 and PSD-95. In conclusion, motor skill abilities, repetitive behaviors, and impaired flexibility to shift habits are associated with reduced striatal excitatory synaptic function in the adult mouse prenatally exposed to VPA.

Environmental enrichment modulates glucocorticoid receptor expression and reduces anxiety in Indian field male mouse Mus booduga through up-regulation of microRNA-124a.

Enriched environmental condition (EC) has been known to reduce anxiety. In this study, we examined whether an EC could enhance anxiolytic behavior in the Indian field mouse Mus booduga by down-regulating the expression of glucocorticoid receptor (GR) through microRNA-124a. Wild individuals were captured at agricultural field, and then housed at standard conditions (SC) for 7days. After short-term at standard condition (STSC), on 8th day they were divided into three groups as those: (i) STSC mice tested on light/dark box on the same day and then euthanized to examine gene expression, (ii) maintained at long-term in standard condition (LTSC) and (iii) transferred to EC. After 30days, both the LTSC and EC groups were tested on the light/dark box and then euthanized to examine gene expression in amygdala region of brain. EC group preferred to stay at light chamber and exhibited less anxiety-like behavioral components when compared to STSC and LTSC groups. However, between the two groups the STSC mice showed lesser anxiety-like behavior than LTSC mice. The expression of Dicer, Ago-2 and microRNA-124a (miR-124a) was more significantly up regulated in EC mice than in STSC and LTSC mice. Furthermore, we have demonstrated that miR-124a binds with 3'UTR of GR, and subsequently we detected a more decreased level of GR in EC than in STSC, LTSC mice. The results suggest that one of the action of EC could be a GR fine tuning through miR-124a, but there is no demonstration that it could be the only involved molecular mechanism.