Investigating the role of oligodendrocytes in a pharmacological model of autism spectrum disorders

Aims: Autism spectrum disorders (ASD) consist of a group of neurodevelopmental conditions characterized by the impairment of both social communication and social interaction (PMID:29398931), accompanying the patient since the first months of life (WHO, 2016). The molecular mechanisms underlying ASD are mostly unknown, but novel evidence demonstrates the involvement of an imbalanced cholesterol/isoprenoid cerebral metabolism (PMIDs:24723866;26655447) which is mainly controlled by oligodendrocytes. These cells are fundamental to sustain myelin sheaths formation so, when dysfunctional, oligodendrocytes become critical for the development of neuropsychiatric disorders like ASD (PMID:27108096). Therefore, aim of this work is to study oligodendrocytes in a pharmacological model of ASD, obtained by the prenatal exposure of male rats to valproate (VPA), an antiepileptic drug that inhibits histone deacetylases, influencing oligodendrocytes differentiation (PMID:23041758). Methods: Prefrontal cortex, cerebellum and hippocampus of infant (postnatal day12, PND12), adolescent (PND40) and adult (PND80) male rats prenatally exposed to VPA have been studied in comparison to their littermates prenatally exposed to saline. Molecular analyses of the oligodendrocytic transcriptional factor Olig2 have been performed by RT-PCR, western blot and immunofluorescence. Results: Our findings showed strong alterations of Olig2 transcription and translation in all brain regions investigated of VPA animals, mainly in the hippocampus. Such impairment was detected at all ages tested, mostly at PND40. Conclusions: Results reveal a wide impairment of oligodendrocytes in ASD, differentially present from childhood to adulthood, in the brain areas mainly involved in ASD and set the basis for future studies to better explain the molecular mechanisms below such alterations.