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Brain Res. 2016 Aug 1;1644:149-60. doi: 10.1016/j.brainres.2016.05.013. Epub 2016 May 10.

Effects of metformin on inflammation and short-term memory in streptozotocin-induced diabetic mice.

Author information

1
Laboratório de Ultraestrutura, Centro de Pesquisas Aggeu Magalhães (CPqAM), PE, Brazil; Programa de Pós-graduação em Ciências Biológicas, Centro de Biociências, Universidade Federal de Pernambuco - UFPE, PE, Brazil. Electronic address: wilmah.oliveira@gmail.com.
2
Laboratório de Ultraestrutura, Centro de Pesquisas Aggeu Magalhães (CPqAM), PE, Brazil.
3
Laboratório de Ultraestrutura, Centro de Pesquisas Aggeu Magalhães (CPqAM), PE, Brazil; Programa de Pós-graduação em Ciências Biológicas, Centro de Biociências, Universidade Federal de Pernambuco - UFPE, PE, Brazil.
4
Laboratório de Ultraestrutura, Centro de Pesquisas Aggeu Magalhães (CPqAM), PE, Brazil; Laboratório de Plasticidade Neuromuscular, Universidade Federal de Pernambuco - UFPE, PE, Brazil.
5
Universidade Federal de Pernambuco - UFPE, Campus Vitória de Santo Antão, PE, Brazil.
6
Laboratório de Ultraestrutura, Centro de Pesquisas Aggeu Magalhães (CPqAM), PE, Brazil. Electronic address: peixoto.christina@gmail.com.

Abstract

The aim of the present study was to analyze the action of metformin on short-term memory, glial cell activation and neuroinflammation caused by experimental diabetic encephalopathy in C57BL/6 mice. Diabetes was induced by the intraperitoneal injection of a dose of 90mg/kg of streptozotocin on two successive days. Mice with blood glucose levels ≥200dl/ml were considered diabetic and were given metformin hydrochloride at doses of 100mg/kg and 200mg/kg (by gavage, twice daily) for 21 days. On the final day of treatment, the mice underwent a T-maze test. On the 22nd day of treatment all the animals were anesthetized and euthanized. Diabetic animals treated with metformin had a higher spatial memory score. The hippocampus of the diabetic animals presented reactive gliosis, neuronal loss, NF-kB signaling activation, and high levels of IL-1 and VEGF. In addition, the T-maze test scores of these animals were low. Treatment with metformin reduced the expression of GFAP, Iba-1 (astrocyte and microglial markers) and the inflammation markers (p-IKB, IL-1 and VEGF), while enhancing p-AMPK and eNOS levels and increasing neuronal survival (Fox-1 and NeuN). Treatment with metformin also improved the spatial memory scores of diabetic animals. In conclusion, the present study showed that metformin can significantly reduce neuroinflammation and can decrease the loss of neurons in the hippocampus of diabetic animals, which can subsequently promote improvements in spatial memory.

KEYWORDS:

Diabetic brain; Diabetic encephalopathy; Impairment cognitive; Type 1 diabetes

PMID:
27174003
DOI:
10.1016/j.brainres.2016.05.013
[Indexed for MEDLINE]
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