Enhancement of synaptic plasticity and reversal of impairments in motor and cognitive functions in a mouse model of Angelman Syndrome by a small neurogenic molecule, NSI-189.

Enhancement of synaptic plasticity and reversal of impairments in motor and cognitive functions in a mouse model of Angelman Syndrome by a small neurogenic molecule, NSI-189. Neuropharmacology. 2018 Nov 05;: Authors: Liu Y, Johe K, Sun J, Hao X, Wang Y, Bi X, Baudry M Abstract NSI-189 Phosphate, (4-benzylpiperazin-1-yl)-[2-(3-methyl-butylamino)pyridin-3-yl] methanone is a new chemical entity under development for the treatment of MDD, based upon preclinical data demonstrating stimulation of neurogenesis of human hippocampus-derived neural stem cells in vitro and in mouse hippocampus in vivo. Previous studies have examined the tolerability and efficacy of NSI-189 for treating major depressive disorder (MDD). NSI-189 has shown significant potential as a treatment for MDD, with concurrent improvement of a cognition scale in a small double-blind, placebo-controlled study. The current study evaluated its possible application for the treatment of Angelman Syndrome. Incubation of acute hippocampal slices from wild-type mice with NSI-189 resulted in a time- and dose-dependent increase in the magnitude of long-term potentiation (LTP) elicited by theta burst stimulation (TBS). The same protocol enhances TBS-induced LTP in acute hippocampal slices from AS mice. A short treatment with daily injections of NSI-189 in AS mice reversed impairments in cognitive and motor functions, while it slightly enhanced performance of WT mice. The effects of NSI...
Source: Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Neuropharmacology Source Type: research