An adenoviral vector encoded with the GPx-1 gene attenuates memory impairments induced by β-amyloid (1-42) in GPx-1 KO mice via activation of M1 mAChR-mediated signaling.

An adenoviral vector encoded with the GPx-1 gene attenuates memory impairments induced by β-amyloid (1-42) in GPx-1 KO mice via activation of M1 mAChR-mediated signaling. Free Radic Res. 2020 Nov 23;:1-42 Authors: Shin EJ, Lee SH, Sharma N, Nguyen BT, Chung YH, Kang SW, Nah SY, Lee YJ, Nabeshima T, Jeong JH, Kim HC Abstract In the present study, we examined whether glutathione peroxidase-1 (GPx-1), a major H2O2 scavenger in the brain, affects memory deficits induced by Aβ (1-42) in mice. Treatment with 400 pmol/5μl Aβ (1-42) (i.c.v.) resulted in a reduction of GPx-1 expression in wild type (WT) mice. An Aβ (1-42)-induced reduction in acetylcholine (ACh) level was observed in the hippocampus. Treatment with Aβ (1-42) consistently resulted in reduced expression and activity of choline acetyltransferase (ChAT) and in an increase in expression and activity of acetylcholinesterase (AChE). Upon examining each of the muscarinic acetylcholine receptors (mAChRs) and nicotinic AChRs, we noted that Aβ (1-42) treatment selectively reduced the levels of M1 mAChR. In addition, Aβ (1-42) induced a significant reduction in phospho-cAMP response element-binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) expression. The cholinergic impairments induced by Aβ (1-42) were more pronounced in GPx-1 knockout mice than in WT mice. Importantly, an adenoviral vector encoded with the GPx-1 gene (Ad-GPx-1) significantly rescued Aβ ...
Source: Free Radical Research - Category: Research Tags: Free Radic Res Source Type: research