SB203580 reverses memory deficits and depression-like behavior induced by microinjection of Aβ1-42 into hippocampus of mice.

Abstract:

:A high co-morbidity between Alzheimer's disease (AD) and depression suggests there might be similar mechanisms underlying the course of these diseases. Previous studies have shown that p38MAPK plays a critical role in the pathophysiology of AD and depression. However, little is known about whether SB203580, a selective inhibitor of p38MAPK, may protect against AD-associated cognitive impairments and depression-like behavior, simultaneously. Herein, we have shown, for the first time, that SB203580 may reverse memory impairments and depression-like behavior induced by hippocampal infusion of β-amyloid 1-42 (Aβ1-42), as measured by novel object recognition, Morris water maze, tail-suspension and forced-swimming tests. In addition, phorbol 12-myristate 13-acetate (PMA), a PKC activator which also activates p38MAPK, significantly abolished the effects of SB203580. Moreover, Aβ1-42 causes increased phosphorylation of p38MAPK and decreased phosphorylation of Ser9-glycogen synthase kinase 3β (GSK3β) and cAMP-response element binding protein (CREB) in the hippocampus of mice, which could be significantly reversed by SB203580. Our results suggest that SB203580 reversed Aβ1-42-induced cognitive impairments and depression-like behavior via inhibiting p38MAPK signaling pathway, which not only supports p38MAPK as a therapeutic target for AD-associated cognitive dysfunction and depression-like behavior, but also provides experimental basis for the use of SB203580 in co-morbidity of AD and depression.

journal_name

Metab Brain Dis

journal_title

Metabolic brain disease

authors

Guo J,Chang L,Li C,Li M,Yan P,Guo Z,Wang C,Zha Q,Wang Q

doi

10.1007/s11011-016-9880-4

subject

Has Abstract

pub_date

2017-02-01 00:00:00

pages

57-68

issue

1

eissn

0885-7490

issn

1573-7365

pii

10.1007/s11011-016-9880-4

journal_volume

32

pub_type

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