Recovery of the synaptic transmission genomic fabrics in the hypothalamic paraventricular nucleus of a rat model of autism treated with ACTH

ABSTRACT: We profiled the whole transcriptomes of male and female rat hypothalamic paraventricular nuclei to determine the remodeling of the genomic fabrics responsible for the glutamatergic, GABAergic, dopaminergic, cholinergic and serotonergic transmission in epilepsy and recovery following treatment with ACTH. The rats were prenatally exposed (G15) to betamethasone followed by repeated adiministration of N-Methyl-D-Aspartic acid (NMDA) on postnatal days 12, 13 and 15 which triggered infantile spasms. Pups were treated with ATCH on days 13, 14 and 15 prior to NMDA administration to determine what effects the treatment had on transcriptome recovery. Our Genomic Fabric Paradigm (GFP) is proposed as a transformative research approach to enhance the understanding of the brain transcriptomic alterations in epileptic rats and recovery following various treatments. The genomic fabric of a particular synapse is the structured transcriptome associated with the most interconnected and stably expressed gene network responsible for that type of neurotransmission. GFP refines the description of functional pathways by selecting the most prominent genes and determining their networking. Moreover, it quantifies the remodeling of functional pathways and their interplay in disease and recovery in response to a treatment. We found that priming with betamethasone had substantial consequences on the topology of the genomic fabrics of all kind of synaptic transmission and that NMDA-induced spasms strongly exacerbated the remodeling of these fabrics. ACTH treatment induced a moderate recovery of the normal synaptic transcriptomes.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE124615 | GEO | 2019/01/04

REPOSITORIES: GEO