Adenylate cyclase activator forskolin alleviates intracerebroventricular propionic acid-induced mitochondrial dysfunction of autistic rats

Abstract

Neuronal mitochondrial dysfunction increases inflammatory mediators and leads to free radical generation and anti-oxidant enzymatic alterations, which are major neuropathological hallmarks responsible for autism. Mitochondrial dysfunction in autism is associated with decreased ATP levels due to reduced levels of cyclic adenosine monophosphate. Rat models of autism were established by intracerebroventricular injection of propionic acid. These rat models had memory dysfunction, decreased muscle coordination and gait imbalance. Biochemical estimation of propionic acid-treated rats showed changes in enzyme activity in neuronal mitochondrial electron transport chain complexes and increases in pro-inflammatory cytokines, oxidative stress and lipid biomarkers. Oral administration of 10, 20 and 30 mg/kg adenylate cyclase activator forskolin for 15 days reversed these changes in a dose-dependent manner. These findings suggest that forskolin can alleviate neuronal mitochondrial dysfunction and improve neurological symptoms of rats with autism. This study was approved by the RITS/IAEC, SIRSA, HARYANA on March 3, 2014 (approval No. RITS/IAEC/2014/03/03).

Keywords

• adenylate cyclase; atp; autism; forskolin; mitochondrial dysfunction; neuroinflammation; oxidative stress; propionic acid