Abstract
Several studies have documented the role of hyper-activation of extracellular signal-regulated kinases (ERK) in Autism pathogenesis. Alpha-mangostin (AMG) is a phytoconstituents with anti-oxidants, anti-inflammatory, and ERK inhibition properties in many diseases. Our research aims to investigate the neuroprotective effect of AMG in the rat model of intracerebroventricular-propionic acid (ICV-PPA) induced autism with a confirmation of its effect on the ERK signaling. Autism was induced in Wistar rats (total 36 rats; 18 male/18 female) by multiple doses of PPA through ICV injection for 11 days. Actophotometer and beam walking tasks were used to evaluate animals’ motor abilities, and the Morris water maze task was utilized to confirm the cognition and memory in animals. Long term administration of AMG100 mg/kg and AMG200 mg/kg continued from day 12 to day 44 of the experiment. Before that, animals were sacrificed, brains isolated, morphological, gross pathological studies were performed, and neurochemical analysis was performed in the brain homogenates. Cellular and molecular markers, including ERK, myelin basic protein, apoptotic markers including caspase-3, Bax, Bcl-2, neuroinflammatory markers, neurotransmitters, and oxidative stress markers, have been tested throughout the brain. Thus, AMG reduces the overactivation of the ERK signaling and also restored autism-like behavioral and neurochemical alterations.
Highlights
Autism is a complex neurodevelopmental condition that indicates language disability, repetitive and irregular social interaction movements, sensory disturbances, hyperactivity, and occasionally symptoms of self-injury [1]
A significant reduction in the bodyweight of the propionic acid (PPA) group was conducted at the end of the experimental protocol (p < 0.0001)
Long-term therapy with 100 mg/kg AMG and 200 mg/kg AMG on days 23 and 33 restored body weight loss relative to the group treated with PPA [two-way ANOVA: F(20,120) = 551.3; p < 0.0001]
Summary
Autism is a complex neurodevelopmental condition that indicates language disability, repetitive and irregular social interaction movements, sensory disturbances, hyperactivity, and occasionally symptoms of self-injury [1]. Multiplestudies have shown that different factors such as heavy metals (Mercury) [2], valproic acid and thalidomide [3], cosmetics and perfumes [4], environmental toxicity [5], gene mutation [6], and intestinal dysbiosis [7] contribute to the pathogenesis of autism. ASD (autism spectrum disorder) affects 1–2 percent of the population and is five percent more common in adult males than females. 10 million children who are vulnerable to autism, i.e., 1–1.5% or 1 out of 66 children under the age of 2–9, are affected in India [8].
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