Ameliorative effect of nicergoline on cognitive function through the PI3K/AKT signaling pathway in mouse models of Alzheimer's disease.
Mol Med Rep
; 17(5): 7293-7300, 2018 05.
Article
em En
| MEDLINE
| ID: mdl-29568940
ABSTRACT
Alzheimer's disease is one of the most common ageassociated diseases that frequently leads to memory disorders, cognitive decline and dementia. Evidence suggests that nicergoline serves an important role in the apoptosis of hippocampal cells, memory recovery, cognitive function and neuronal survival. However, the signaling pathway affected by nicergoline treatment remains to be elucidated. The purpose of the present study was to investigate the role of nicergoline in the cognitive competence of a mouse model of Alzheimer's disease. The apoptosis rates of hippocampal cells were studied in mice with Alzheimer's disease treated with nicergoline compared with the negative control. Apoptosisassociated gene expression levels in hippocampal cells, and hippocampus area, were analyzed in the experimental mice. Visual attention and inhibitory control were assessed and neural counting was performed in brain regions of interest. The phosphatidylinositol 3kinase (PI3K)/RACα serine/threonineprotein kinase (AKT) signaling pathway was additionally analyzed in hippocampal cells following treatment with nicergoline. The results of the present study demonstrated that nicergoline ameliorated apoptosis in hippocampal cells and hippocampus tissue in 3xTgAD mice with Alzheimer's disease. The data indicated that apoptosisassociated genes, including caspase3, BCL2 associated X, BH3 interacting domain death agonist and caspase9, were downregulated in hippocampal cells isolated from nicergoline-treated experimental mice. In addition, the expression levels of inflammatory factors, in addition to oxidative stress, were decreased in hippocampal cells treated with nicergoline. Additionally, amyloid precursor protein accumulation was cleared in the hippocampal area in nicergolinetreated mice. Nicergoline inhibited neuronal loss and prevented cognitive impairment through the restoration of learning/memory ability. It was additionally demonstrated in the present study that nicergoline improved motor attention impairment and cognitive competence in hippocampal cells by acting on the PI3K/AKT signaling pathway. Therefore, memory recovery, cognitive function and neuronal survival were repaired by nicergoline via inhibition of the PI3K/AKT signaling pathway, suggesting that nicergoline may be an efficient drug for the clinical treatment of patients with Alzheimer's disease.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cognição
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Nootrópicos
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Fármacos Neuroprotetores
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Proteínas Proto-Oncogênicas c-akt
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Fosfatidilinositol 3-Quinase
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Doença de Alzheimer
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Nicergolina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Mol Med Rep
Ano de publicação:
2018
Tipo de documento:
Article