Neuroprotective potential of solanesol in intracerebroventricular propionic acid induced experimental model of autism: Insights from behavioral and biochemical evidence

Abstract

Autism is the category used within the newest edition of the diagnostic and statistical manual of neurodevelopmental disorders. Autism is a spectrum of disorder where a variety of behavioural patterns observed in autistic patients, such as stereotypes and repetitive behavior, hyperexcitability, depression-like symptoms, and memory and cognitive dysfunctions. Neuropathological hallmarks that associated with autism are mitochondrial dysfunction, oxidative stress, neuroinflammation, Neuro-excitation, abnormal synapse formation, overexpression of glial cells in specific brain regions like cerebellum, cerebral cortex, amygdala, and hippocampus. ICV injection of propionic acid (PPA) (4 μl/0.26 M) mimics autistic-like behavioral and biochemical alterations in rats. Literature findings reveal that there is a link between autism neuronal mitochondrial coenzyme-Q10 (CoQ10) and ETC-complexes dysfunctions are the keys pathogenic events for autism. Therefore, in the current study, we explore the neuroprotective interventions of Solanesol (SNL) 40 and 60 mg/kg alone and in combination with standard drugs Aripiprazole (ARP) 5 mg/kg, Citalopram (CTP) 10 mg/kg, Memantine (MEM) 5 mg/kg and Donepezil (DNP) 3 mg/kg to overcome behavioral and biochemical alterations in PPA induced experimental model of Autism. Chronic treatment with SNL 60 mg/kg in combination with standard drug shows a marked improvement in locomotion, muscle coordination, long-term memory and the decrease in depressive behavior. While, chronic treatment of SNL alone and in combination with standard drug aripiprazole, citalopram, donepezil, and memantine shows the Neuroprotective potential by enhancing the cognitive deficits, biochemical alterations along with reducing the level of inflammatory mediators and oxidative stress. Keywords: Autism, mitochondrial dysfunction, Coenzyme-Q10, Propionic acid, ATP, Aripiprazole, Memantine, Citalopram, Donepezil