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.

Empagliflozin reduces vascular damage and cognitive impairment in a mixed murine model of Alzheimer’s disease and type 2 diabetes

“…Likewise, hypoglycemic agents show anti-inflammatory activity [41]. Moreover, these antiinflammatory effects are also detected at the central level with metformin [42], liraglutide [43], multitarget agents [28], or combined therapies [12]. In our hands, EMP also reduced microglia burden in the parenchyma from db/db and APP/PS1xdb/db mice.…”

Metabolic and Cognitive Effects of Ranolazine in Type 2 Diabetes Mellitus: Data from an in vivo Model

“…Metformin has been suggested to exert positive effects on cognitive decline by acting both indirectly, decreasing blood glucose levels, and directly at the level of CNS [39].…”

Liraglutide prevents cognitive decline in a rat model of streptozotocin-induced diabetes independently from its peripheral metabolic effects

“…The precise pathophysiology of cognitive dysfunction and neuronal damage in T2DM is not completely understood, but it is likely that impaired glucose control (hyperglycemia, hypoglycemia), vascular damage, and insulin resistance play significant roles [3]. None of the known antidiabetic drugs currently used for T2DM has a proven effect on cognitive decline in patients, even if, there are some data on the efficacy of metformin and other antidiabetic drugs in animal models of diabetes and Alzheimer's disease (AD) [4][5][6] however, the glucagon-like peptide-1 receptor (GLP-1R) agonists, a new class of antidiabetic drugs now used therapeutically in diabetic patients, also exert powerful neuroprotective properties in animal models of neurodegenerative diseases, cerebral ischemia and traumatic brain injury [7,8], therefore might be valuable therapeutic tools for prevention of neurological comorbidity in T2DM. GLP-1 is an endogenous incretin (insulinotropic) peptide hormone secreted from the gastrointestinal tract, that plays a key physiological role in glucose homeostasis by enhancing pancreatic insulin secretion and by suppressing glucagon release and hepatic glucose output [9].…”