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Protective role of Apelin-13 on amyloid β25-35-induced memory deficit; Involvement of autophagy and apoptosis process.

Abstract：

:Alzheimer's disease (AD) by progressive neurodegenerative pattern is associated with autophagy stress which is suggested as a potential cause of amyloid β (Aβ) aggregation and neural loss. Apelin-13, a neuropeptide with modulatory effect on autophagy, has been shown the beneficial effects on neural cell injuries. We investigated the effect of Apelin-13 on Aβ-induced memory deficit as well as autophagy and apoptosis processes. We performed bilateral intra-CA1 injection of Aβ25-35 alone or in combination with Apelin-13. Spatial reference and working memory was evaluated using the Morris water maze (MWM) and Y-maze tests. Hippocampus was harvested on 2, 5, 10 and 21 days after Aβ injection. The light chain 3 (LC3II/I) ratio, histone deacetylase 6 (HDAC6) level, Caspase-3 cleavage, and mTOR phosphorylation were assessed using western blot technique. Intra-CA1 injection of Aβ caused impairment of working and spatial memory. We observed higher LC3II/I ratio, cleaved caspase-3 and lower HDAC6, and p-mTOR/mTOR ratio in Aβ-treated animals. Apelin-13 provided significant protection against the destructive effects of Aβ on working and spatial memory. Apelin-13 prevented the increase of LC3II/I ratio and cleaved caspase-3 on days 10 and 21 after injection of Aβ. It also limited the Aβ-induced reduction in HDAC6 expression. This implies that Apelin-13 has suppressed both autophagy and apoptosis. Our findings suggested that the neuroprotection of Apelin-13 may be in part related to autophagy and apoptosis inhibition via the mTOR signaling pathway. Apelin-13 may be a promising approach to improve memory impairment and potentially pave the way for new therapeutic plans in AD.

journal_name

Prog Neuropsychopharmacol Biol Psychiatry

journal_title

Progress in neuro-psychopharmacology & biological psychiatry

authors

Aminyavari S,Zahmatkesh M,Farahmandfar M,Khodagholi F,Dargahi L,Zarrindast MR

doi

10.1016/j.pnpbp.2018.10.005

subject

Has Abstract

pub_date

2019-03-08 00:00:00

pages

322-334

eissn

0278-5846

issn

1878-4216

pii

S0278-5846(18)30155-6

journal_volume

pub_type

杂志文章

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Protective role of Apelin-13 on amyloid β25-35-induced memory deficit; Involvement of autophagy and apoptosis process.