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.
Highlights
Autism is a stereotypical disorder of the center nerves system (CNS), having the involvement of communication gap, repetitive behavioral patterns and restricted interests, hyperactivity and sensory disturbances
There are a variety of approachable drug therapies used clinically to provide symptomatic relief in autistic patients, such as aripiprazole (ARP) [63], memantine (MEM) [18], donepezil (DNP) [34] and citalopram (CTP) [44] in attenuation of behavioral alterations
The animals kept in polyacrylic cages with a wire mesh top and soft bedding. They kept under standard husbandry conditions of 12 hour light and dark cycle with food and water ad libitum maintained at 23 2 The experimental protocol approved by the Institutional Animal Ethics Committee (IAEC) with registration no. 816/PO/ReBiBt/S/04/ CPCSEA as per the guidelines of the Committee for the purpose of control and supervision of experiments on animals, Government of India (ISFCP/IAEC/CPCSEA/Meeting No.23/2018/ Protocol No 378)
Summary
Autism is a stereotypical disorder of the center nerves system (CNS), having the involvement of communication gap, repetitive behavioral patterns and restricted interests, hyperactivity and sensory disturbances. Propionic acid (PPA) is a short-chain fatty acid endogenous to the human body as both an intermediary of fatty acid metabolism and a metabolic end-product of enteric gut bacteria such as Clostridia and Abbreviations: ETC, electron-transport chain; PPA, propionic acid; CoQ10, coenzyme-Q10; SNL, Solanesol; CNS, center nerves system; UBE3A, Ubiquitin-protein ligase E3A; MAPK3, mitogen-activated protein kinase 3; BBB, blood-brain barrier; MEM, Memantine; ARP, Aripiprazole; CTP, Citalopram; DNP, Donepezil; i.p., Intraperitoneal route; ELT, escape latency; LDH, lactate dehydrogenase; AChE, acetylcholinesterase acetylcholinesterase; MDA, malondialdehyde; SOD, superoxide dismutase; NO, nitric oxide; ICV, Intracerebroventricular; p.o., Oral. There are a variety of approachable drug therapies used clinically to provide symptomatic relief in autistic patients, such as aripiprazole (ARP) [63], memantine (MEM) [18], donepezil (DNP) [34] and citalopram (CTP) [44] in attenuation of behavioral alterations. The current study explored the neuroprotective effect of chronic administration of SNL as a neuroprotective agent by administering alone and in combination with standard drugs Aripiprazole (ARP), memantine (MEM), donepezil (DNP) and citalopram (CTP) in ICV-PPA induces autistic rats
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