Metformin prevents p-tau and amyloid plaque deposition and memory impairment in diabetic mice.

Autor: Oliveira WH; Postgraduate Program in Biological Sciences/Center of Biosciences, Federal University of Pernambuco (UFPE), Recife, PE, CEP 50670-420, Brazil.; Laboratory of Ultrastructure, Aggeu Magalhães Institute (IAM), FIOCRUZ, Av. Moraes Rego S/N, Recife, PE, Brazil., Braga CF; Laboratory of Ultrastructure, Aggeu Magalhães Institute (IAM), FIOCRUZ, Av. Moraes Rego S/N, Recife, PE, Brazil., Lós DB; Postgraduate Program in Biotechnology/Northeast Network in Biotechnology (RENORBIO), Federal University of Pernambuco (UFPE), Recife, PE, Brazil., Araújo SMR; Postgraduate Program in Biological Sciences/Center of Biosciences, Federal University of Pernambuco (UFPE), Recife, PE, CEP 50670-420, Brazil., França MR; Postgraduate Program in Biological Sciences/Center of Biosciences, Federal University of Pernambuco (UFPE), Recife, PE, CEP 50670-420, Brazil.; Laboratory of Ultrastructure, Aggeu Magalhães Institute (IAM), FIOCRUZ, Av. Moraes Rego S/N, Recife, PE, Brazil.; Postgraduate Program in Biotechnology/Northeast Network in Biotechnology (RENORBIO), Federal University of Pernambuco (UFPE), Recife, PE, Brazil.; Postgraduate Program in Biosciences and Biotechnology for Health (PPGBBS), Oswaldo Cruz Foundation (FIOCRUZ-PE)/Aggeu Magalhães Institute (IAM), Recife, PE, Brazil.; Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Rio de Janeiro, Brazil., Duarte-Silva E; Laboratory of Ultrastructure, Aggeu Magalhães Institute (IAM), FIOCRUZ, Av. Moraes Rego S/N, Recife, PE, Brazil.; Postgraduate Program in Biosciences and Biotechnology for Health (PPGBBS), Oswaldo Cruz Foundation (FIOCRUZ-PE)/Aggeu Magalhães Institute (IAM), Recife, PE, Brazil., Rodrigues GB; Postgraduate Program in Biological Sciences/Center of Biosciences, Federal University of Pernambuco (UFPE), Recife, PE, CEP 50670-420, Brazil.; Laboratory of Ultrastructure, Aggeu Magalhães Institute (IAM), FIOCRUZ, Av. Moraes Rego S/N, Recife, PE, Brazil., Rocha SWS; Postgraduate Program in Biological Sciences/Center of Biosciences, Federal University of Pernambuco (UFPE), Recife, PE, CEP 50670-420, Brazil., Peixoto CA; Laboratory of Ultrastructure, Aggeu Magalhães Institute (IAM), FIOCRUZ, Av. Moraes Rego S/N, Recife, PE, Brazil. peixoto.christina@gmail.com.; Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Rio de Janeiro, Brazil. peixoto.christina@gmail.com.
Jazyk: angličtina
Zdroj: Experimental brain research [Exp Brain Res] 2021 Sep; Vol. 239 (9), pp. 2821-2839. Date of Electronic Publication: 2021 Jul 20.
DOI: 10.1007/s00221-021-06176-8
Abstrakt: Insulin deficiency or resistance can promote dementia and hallmarks of Alzheimer's disease (AD). The formation of neurofibrillary tangles of p-TAU protein, extracellular Aβ plaques, and neuronal loss is related to the switching off insulin signaling in cognition brain areas. Metformin is a biguanide antihyperglycemic drug used worldwide for the treatment of type 2 diabetes. Some studies have demonstrated that metformin exerts neuroprotective, anti-inflammatory, anti-oxidant, and nootropic effects. This study aimed to evaluate metformin's effects on long-term memory and p-Tau and amyloid β modulation, which are hallmarks of AD in diabetic mice. Swiss Webster mice were distributed in the following experimental groups: control; treated with streptozotocin (STZ) that is an agent toxic to the insulin-producing beta cells; STZ + metformin 200 mg/kg (M200). STZ mice showed significant augmentation of time spent to reach the target box in the Barnes maze, while M200 mice showed a significant time reduction. Moreover, the M200 group showed reduced GFAP immunoreactivity in hippocampal dentate gyrus and CA1 compared with the STZ group. STZ mice showed high p-Tau levels, reduced p-CREB, and accumulation of β-amyloid (Aβ) plaque in hippocampal areas and corpus callosum. In contrast, all these changes were reversed in the M200 group. Protein expressions of p-Tau, p-ERK, pGSK3, iNOS, nNOS, PARP, Cytochrome c, caspase 3, and GluN2A were increased in the parietal cortex of STZ mice and significantly counteracted in M200 mice. Moreover, M200 mice also showed significantly high levels of eNOS, AMPK, and p-AKT expression. In conclusion, metformin improved spatial memory in diabetic mice, which can be associated with reducing p-Tau and β-amyloid (Aβ) plaque load and inhibition of neuronal death.
(© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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