Aarti Tiwari1, Rishabh Khera1, Saloni Rahi1, Sidharth Mehan1, Hafiz Antar Makeen2, Yahya H Khormi3, Muneeb U Rehman4, Andleeb Khan5. 1. Department of Pharmacology, Neuropharmacology Division, ISF College of Pharmacy, Moga, Punjab 142001, India. 2. Department of Clinical Pharmacy, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia. 3. Division of Neurosurgery, Department of Surgery, Faculty of Medicine, Jazan University, Jazan, 45142, Saudi Arabia. 4. Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia. 5. Department of Pharmacology & Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia.
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 AMG 100 mg/kg and AMG 200mg/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.
Several studies have documented the role of hyper-activation of extracellular signal-regulated kinases (ERK) in pan class="Disease">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 AMG 100 mg/kg and AMG 200mg/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.
Authors: Bruce D Trapp; Megan Vignos; Jessica Dudman; Ansi Chang; Elizabeth Fisher; Susan M Staugaitis; Harsha Battapady; Sverre Mork; Daniel Ontaneda; Stephen E Jones; Robert J Fox; Jacqueline Chen; Kunio Nakamura; Richard A Rudick Journal: Lancet Neurol Date: 2018-08-22 Impact factor: 44.182