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Involvement of PI3K/Akt/GSK-3β signaling pathway in the antidepressant-like and neuroprotective effects of Morus nigra and its major phenolic, syringic acid.

Abstract：

:Depression is a common neuropsychiatric disorder whose pathophysiology has been associated with glutamatergic excitotoxicity. Thus, the research for new antidepressant strategies with the ability to mitigate glutamate toxicity has received growing attention. Given this background, the present study sought to investigate the antidepressant-like and neuroprotective effects of Morus nigra (MN) and its major phenolic, syringic acid (SA), against glutamate-induced damage, as well as, the role of the PI3K/Akt/GSK-3β signaling pathway in these effects. Treatment with MN (3 mg/kg) and SA (1 mg/kg) for 7 days, similar to fluoxetine (10 mg/kg), triggered an antidepressant-like effect. Moreover, the treatments evoked neuroprotection against glutamatergic excitotoxicity in hippocampal slices, and MN treatment also afforded protection in cerebrocortical slices. Notably, ex vivo neuroprotective effect of MN and SA was mediated, at least in part, by PI3K/Akt/GSK-3β signaling pathway. Furthermore, the ability of MN and SA to counteract the glutamate-induced damage were evaluated in three different in vitro experiments. The hippocampal slices pretreated with MN (0.05 and 0.1 μg/mL) or SA (0.01-0.1 μg/mL) as well as the concomitant treatment with MN (0.01 and 0.05 μg/mL) or SA (0.05 and 0.1 μg/mL) exhibited protection against glutamate toxicity. Interestingly, post-treatment with MN in all doses (0.01-0.1 μg/mL) and SA at dose of 0.1 μg/mL were capable of preventing glutamate-induced cell death. In vitro neuroprotective effect of SA, but not MN, involves the activation of Akt, since the pretreatment with LY294002 completely abolished the protective effect. Overall, MN and SA presented antidepressant-like and neuroprotective effects against glutamatergic excitotoxicity via PI3K/Akt/GSK-3β.

journal_name

Chem Biol Interact

journal_title

Chemico-biological interactions

authors

Dalmagro AP,Camargo A,Severo Rodrigues AL,Zeni ALB

doi

10.1016/j.cbi.2019.108843

subject

Has Abstract

pub_date

2019-12-01 00:00:00

pages

108843

eissn

0009-2797

issn

1872-7786

pii

S0009-2797(19)30901-9

journal_volume

314

pub_type

杂志文章

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Involvement of PI3K/Akt/GSK-3β signaling pathway in the antidepressant-like and neuroprotective effects of Morus nigra and its major phenolic, syringic acid.