Activation of The social decision-making network in valproate-treated, autism-model mice

01/29/2020

Szilvia Márta Papp¹, Ágota Ádám¹, András Csillag¹, László gerecsei¹, Gergely Zachar¹, róbert gergely kemecsei¹

¹ Semmelweis university, department of anatomy, histology and embryology

The Autism Spectrum Disorder (ASD) is a lifelong neurodevelopmental disease that is extensively prevalent and males are multiple times more affected than females. ASD any degree of severity, is clinically characterized by social behaviour impairments in, mainly involving difficulties in non-sexual social situations. Despite a complex genetic background, exposure to specific agents, such as valproic acid (VPA) during pregnancy, have been linked to ASD. In the current experiment we used the VPA-mouse model of ASD, investigating changes of the social decision-making network of brain regions (SDMN) of juvenile male mice in the light of several social settings. The efficacy of VPA treatment was validated by three-chamber behaviour test, commonly accepted for measuring the ASD-like effects of VPA exposure. c-Fos immunohistochemistry was performed in healthy and VPA-treated individuals in order to capture snapshots of the momentary activity of cells of the SDMN during two types of social situation: (1) separated from familiar companion and kept alone for one day; (2) separated for one day and then reinstated to familiar cagemates. Video was taken of the reunion and of a control situation. Certain brain regions of the SDMN showed marked differences according to social situations and treatments: e.g. the lateral septum, which plays major role in regulating social stress, showed increased activity after the reinstatement in healthy individuals in contrast to VPA treated mice. Exposure to valproic acid most likely disrupts the SDMN and, therefore, affects the social interactions from early postnatal development, further hindering the acquisition of normal social behaviour.