The dual-active histamine H3 receptor antagonist and acetylcholine esterase inhibitor E100 ameliorates stereotyped repetitive behavior and neuroinflammmation in sodium valproate induced autism in mice

Chemico-biological Interactions
Nermin EissaBassem Sadek

Abstract

Postnatal exposure to valproic acid (VPA) in rodents induces autism-like neurobehavioral defects which are comparable to the motor and cognitive deficits observed in humans with autism spectrum disorder (ASD). Histamine H3 receptor (H3R) and acetylcholine esterase (AChE) are involved in several cognitive disorders such as Alzheimer's disease, schizophrenia, anxiety, and narcolepsy, all of which are comorbid with ASD. Therefore, the present study aimed at evaluating effect of the novel dual-active ligand E100 with high H3R antagonist affinity and balanced AChE inhibition on autistic-like repetitive behavior, anxiety parameters, locomotor activity, and neuroinflammation in a mouse model of VPA-induced ASD in C57BL/6 mice. E100 (5, 10, and 15 mg/kg) dose-dependently and significantly ameliorated repetitive and compulsive behaviors by reducing the increased percentages of nestlets shredded (all P < 0.05). Moreover, pretreatment with E100 (10 and 15 mg/kg) attenuated disturbed anxiety levels (P < 0.05) but failed to restore the hyperactivity observed in the open field test. Furthermore, pretreatment with E100 (10 mg/kg) the increased microglial activation, proinflammatory cytokines and expression of NF-κB, iNOS, and COX-2 in the cer...Continue Reading

Citations

Oct 2, 2019·Indian Journal of Pharmacology·R Ashish JainBikash Medhi
Nov 20, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Alaa AlachkarBassem Sadek
Oct 28, 2020·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Alinne Lorrany Gomes Dos SantosDaniel Guerreiro Diniz
Mar 26, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Abdoh TalebFeng Han
Sep 4, 2020·European Journal of Medicinal Chemistry·Dorota ŁażewskaKatarzyna Kieć-Kononowicz
Mar 28, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Karthikkumar VenkatachalamBassem Sadek
Jul 17, 2021·Frontiers in Molecular Neuroscience·Elzbieta ZieminskaJerzy W Lazarewicz
Aug 3, 2021·Frontiers in Neuroscience·Elliott Carthy, Tommas Ellender
Aug 19, 2020·Developmental Neuroscience·Devahuti ChalihaJohn Mamo

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