Oxiracetam and Zinc Ameliorates Autism-Like Symptoms in Propionic Acid Model of Rats

摘要

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by restrictive behaviour, deficit in social skills and interaction. The multifactorial etiology, complex pathophysiology and different combination of symptoms (unusual speech patterns, frequent repetition of phrases) make it difficult to treat. Thus, present study aimed to find the protective effects of oxiracetam alone and in combination with zinc on brain behavioral, biochemical, pro-inflammatory cytokines and neurotransmitters level. Rats were administered with propionic acid (250 mg/kg p.o.) for 3 days and immediately on next day treatment were given with oxiracetam (25, 50 mg/kg i.p), zinc (4 mg/kg) as well as oxiracetam (25 mg/kg i.p) in combination with zinc (4 mg/kg p.o). Behavioral parameters were performed from 22th to 28th day. On 29th day, all the animals were sacrificed by cervical dislocation and the brain was preserved for biochemical (LPO, GSH, nitrite, mitochondrial complex I, IV and cAMP), neuroinflammatory (TNF-alpha, IL-1 beta, IL-6) and neurotransmitters (5-HT, GABA, glutamate and acetylcholine) analysis. The propionic acid administration showed memory impairment, restrictive behavior, increased proinflammatory cytokines level, biochemical and neurotransmitters alteration. However, treatment with oxiracetam alone and in combination with zinc significantly attenuated behavioral, biochemical, inflammatory cytokines and restored neurotransmitters level. The finding of present study demonstrated that oxiracetam alone and in combination with zinc afforded superior anti-autistic effect through antioxidant, anti-inflammatory and anti-excitotoxic mechanisms and could serve as attractive strategy in managing autism.