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.

IGF-1/GLP-1 Signaling Activator 4-hydroxyisoleucine (4-HI) Prevent Neurobehavioral and Neurochemical Defects in Methylmercury-induced Experimental Model of ALS: Insights From CSF, Blood Plasma and Brain Homogenate Samples in Rats

“…The rats were scored for immobility duration when they ceased struggling and remained oating motionless in the upright position by making only small movements to keep their head above water. Immediately following the test, the rats were wrapped in a dry towel and placed under a heating lamp to dry (Sharma et al, 2019).…”

Solanesol Mediated SIRT-1 Signaling Activation Prevents Neurobehavioral and Neurochemical Defects in Ouabain-induced Experimental Model of Bipolar Disorder in Rats

“…The absorbance was spectrophotometrically measured at 480nm after 5 minutes. The activity of SOD was measured in nM/mg of protein (Sharma et al, 2019).…”

“…As a SIRT-1 signalling activator, SNL has been shown to have neuroprotective properties against Alzheimer's disease (Jaiswal et al, 2019), intracerebral haemorrhage (ICH) (Rajdev et al, 2020), and autism (Sharma et al, 2019). It also has neuroprotective bene ts against MS (Sharma et al, 2021) and HD (Mehan et al, 2010).…”

PI3K/AKT/mTOR Signalling Inhibitor Chrysophanol Ameliorates Neurobehavioural and Neurochemical Defects in Propionic Acid-induced Experimental Model of Autism

“…The beam crossing task was conducted on days 1st, 13th, 23rd, and 43rd of the experimental protocol schedule to evaluate motor coordination ability. During each trial, the number of foot slips was recorded, and additionally, the direction of an animal's fall was observed against the cut-off time of ve minutes (Sharma et al, 2019).…”

“…PPA accumulates inside cells, in icting intracellular acidi cation, causes mitochondrial dysfunction (Mehan et al, 2020), elevates oxidative stress markers (Rahi et al, 2021), alters neurotransmitters (Tiwari et al, 2021), and impairs synaptic transmission in autistic rat brains (Meeking et al, 2020). According to Sharma et al, stereotaxic PPA injection into the cerebral cortex area causes stereotypical behaviour, and neurochemical alterations in experimental models of autism in rats (Sharma et al, 2019). PI3K/AKT/mTOR signalling pathway is principally involved in different neuronal functions such as synaptic plasticity, neuronal development, consolidation of memory, and protein synthesis (Kassai et al, 2014;Takei et al, 2014).…”