Intranasally delivered small interfering RNA-mediated suppression of scavenger receptor Mac-1 attenuates microglial phenotype switching and working memory impairment following hypoxia.

Intranasally delivered small interfering RNA-mediated suppression of scavenger receptor Mac-1 attenuates microglial phenotype switching and working memory impairment following hypoxia. Neuropharmacology. 2018 May 05;: Authors: Das S, Mishra KP, Ganju L, Singh SB Abstract Brain, being the highest consumer of oxygen, is prone to increased risk of hypoxia-induced neurological insults. In response to hypoxia, microglia, the major resident immune cells of brain switches to an activated phenotype and promote inflammatory responses leading to tissue damage and loss of cognitive functions including working memory impairment. Till date, no proven clinical therapeutics is available to retard the progression of neurodegenerative memory impairment. In the present study, we investigated the therapeutic potential of intranasal small interfering RNA (siRNA) delivery in a mouse model of hypoxia-induced working memory impairment using microglial receptor, Mac-1 as a target gene. Here, we implicate Mac-1 scavenger receptor in microglial phenotype switching, neurodegeneration in prefrontal cortex, hippocampus and working memory impairment. RNA mediated silencing of Mac-1 in both in vitro and in vivo model showed significant impact of it on hypoxia induced altered expression of Mac-1 endogenous ligand, signaling cascade proteins, transcription factors and NADPH oxidase pathway. Efficient degradation of Mac-1 mRNA suppressed expression of M1 phenotypic m...
Source: Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Neuropharmacology Source Type: research