title: Effects of metformin on inflammation and short-term memory in streptozotocin-induced diabetic mice.
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.
authors.affiliation: 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.
authors.forename: Wilma Helena
authors.initials: WH
authors.lastname: Oliveira
authors.affiliation: Laboratório de Ultraestrutura, Centro de Pesquisas Aggeu Magalhães (CPqAM), PE, Brazil.
authors.forename: Ana Karolina
authors.initials: AK
authors.lastname: Nunes
authors.affiliation: 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.
authors.forename: Maria Eduarda Rocha
authors.initials: ME
authors.lastname: França
authors.affiliation: Laboratório de Ultraestrutura, Centro de Pesquisas Aggeu Magalhães (CPqAM), PE, Brazil.
authors.forename: Laise Aline
authors.initials: LA
authors.lastname: Santos
authors.affiliation: Laboratório de Ultraestrutura, Centro de Pesquisas Aggeu Magalhães (CPqAM), PE, Brazil; Laboratório de Plasticidade Neuromuscular, Universidade Federal de Pernambuco - UFPE, PE, Brazil.
authors.forename: Deniele Bezerra
authors.initials: DB
authors.lastname: Lós
authors.affiliation: Laboratório de Ultraestrutura, Centro de Pesquisas Aggeu Magalhães (CPqAM), PE, Brazil.
authors.forename: Sura Wanessa
authors.initials: SW
authors.lastname: Rocha
authors.affiliation: Universidade Federal de Pernambuco - UFPE, Campus Vitória de Santo Antão, PE, Brazil.
authors.forename: Karla Patrícia
authors.initials: KP
authors.lastname: Barbosa
authors.affiliation: 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.
authors.forename: Gabriel Barros
authors.initials: GB
authors.lastname: Rodrigues
authors.affiliation: Laboratório de Ultraestrutura, Centro de Pesquisas Aggeu Magalhães (CPqAM), PE, Brazil. Electronic address: peixoto.christina@gmail.com.
authors.forename: Christina Alves
authors.initials: CA
authors.lastname: Peixoto
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism* / Q000523:psychology*; D004660:Encephalitis / Q000209:etiology / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D008687:Metformin / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D013311:Streptozocin
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D053583:Interleukin-1beta; D010446:Peptide Fragments; C052994:interleukin-1beta (163-171); D000072000:NF-KappaB Inhibitor alpha; D013311:Streptozocin; D008687:Metformin; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D055372:AMP-Activated Protein Kinases
keywords: Diabetic brain; Diabetic encephalopathy; Impairment cognitive; Type 1 diabetes