Pre-weaning Environmental Enrichment Reduced Hippocampal Level of BDNF and Symptoms Severity in VPA Rat Model of Autism

Abstract

Background & Objective: Due to the lack of early diagnosis, it is unclear how the environmental stimulations in infancy would affect the underlying structures of Autism Spectrum Disorder (ASD), as well as the onset or severity of symptoms. The study aimed to investigate the effects of receiving pre-weaning environmental enrichment on the severity of ASD symptoms and the hippocampal level of brain-derived neurotrophic factor (BDNF) in the valproic acid (VPA) rat model. Materials & Methods: Male rats exposed to valproic acid (VPA) or normal saline (Sal) embryonally (E12.5) were randomly assigned to 4 environments: Standard (ST), pre-weaning environmental enrichment (PEE), secondary environmental enrichment (SEE) and PEE+SEE (EE). Behavioral tests were repeated at postnatal day (PND)30 and PND60, in the light phase with a blinded examiner. The BNDF level was determined at PND68. Results: In VPA rats, receiving PEE, increased social interactions and decreased anxiety, pain sensitivity even in early adulthood. Also, it reduced repetitive behavior but with no significant differences. The BDNF level in VPA-PEE and VPA-SEE was lower than VPA-ST, VPA-EE and saline groups. The biggest improvement in symptom severity was seen in EE. Conclusion: Reduction of symptoms severity in VPA-PEE and the best performance in VPA-EE showed that rich and sensory overflew environment in infancy can change the formation of ASD. Finding might point to hyperactivity or a lack of regulation of BDNF levels in ASD. PEE most likely reduced hyperactivity, and continued environmental enrichment in EE, regulated the level of BDNF in the hippocampus.

Keywords

• pre-weaning environmental enrichment
• post-weaning environmental enrichment
• autism spectrum disorder
• brain-derived neurotrophic factor
• valproic acid