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Geniposide ameliorates cognitive deficits by attenuating the cholinergic defect and amyloidosis in middle-aged Alzheimer model mice.

Abstract：

:Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory deficits and cognitive decline. Amyloid-β (Aβ) deposition and cholinergic defect are widely thought to be the underlying mechanism of learning and memory impairment. Geniposide, which is the main active component of the traditional Chinese herbal Gardenia jasminoides Ellis, elicits neuroprotective effects by alleviating inflammation responses and oxidative damages. In this study, we investigated the protective effect of geniposide on levels of cholinergic markers, RAGE, RAGE-dependent signalling pathways and amyloid accumulation in the APPswe/PS1dE9 AD model mouse. Geniposide suppressed MAPK signaling over-activation mediated by Aβ-RAGE interaction, resulting in reduced Aβ accumulation and amelioration of cholinergic deficits in the cerebral hippocampus. Furthermore, geniposide inhibited the toxic effect of oligomeric Aβ1-42 induced cholinergic deficit by increasing ChAT levels and activity but decreasing AChE activity in cultured primary hippocampal neurons. These results indicated that geniposide enhanced cholinergic neurotransmission, which likely contributes to its memory enhancing effect.

journal_name

Neuropharmacology

journal_title

Neuropharmacology

authors

Zhao C,Zhang H,Li H,Lv C,Liu X,Li Z,Xin W,Wang Y,Zhang W

doi

10.1016/j.neuropharm.2016.12.002

subject

Has Abstract

pub_date

2017-04-01 00:00:00

pages

18-29

eissn

0028-3908

issn

1873-7064

pii

S0028-3908(16)30555-X

journal_volume

116

pub_type

杂志文章

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