Insulin treatment protects the brain against neuroinflammation by reducing cerebral cytokines and modulating mitochondrial function

[Display omitted] •Insulin i.c.v. treatment reverses the LPS effect’s on cognition function.•Insulin i.c.v. treatment reverses the increases on citokynes induced by LPS on brain.•Insulin i.c.v. treatment maintain the mitochondrial function affected by LPS on brain.•Insulin i.c.v. treatment reverses the LPS effect’s on oxidative status on brain.•Insulin used on brain is useful to neurodisease associated with neuroinflammation. In the central nervous system, glial cells protect the brain against neuronal stress by inducing inflammatory responses; namely, intracellular signaling and cytokine production. However, chronic inflammation is often associated with degenerative diseases that can damage hormone signaling and mitochondrial function. Lipopolysaccharide (LPS) induces neuroinflammation by stimulating the production of interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α); moreover, it generates oxidative stress and impairs cognitive functions. The aim of the present study was to assess the therapeutic efficacy of intracerebroventricular (i.c.v.) injections of insulin against neuroinflammation. Inflammation was first induced in male Wistar rats (60 days old, n = 12/group) through an intraperitoneal injection of 0.1 mg/kg LPS. The i.c.v. insulin treatment at a 0.5 mU dose was initiated 4 h later and administered once a day for 5 days. Thereafter, the spatial memory of the rats was assessed, and the hippocampus and cortex were later dissected for biochemical analyses. Our results showed that LPS induced cognitive function impairments, but the insulin treatment reversed these effects. Whereas the levels of brain-derived neurotrophic factor and beta-nerve growth factor in the hippocampus were not altered by LPS, they were decreased in the cortex by insulin. The IL-1β and TNF-α levels were increased in the cortex and hippocampus following exposure to LPS, but insulin reversed these effects. Evaluation of the H2O2levels and mitochondrial membrane potential revealed that LPS modulated mitochondrial function, an effect that was also reversed by insulin. Moreover, LPS induced oxidative stress by decreasing the superoxide dismutase and catalase activities and glutathione and sulfhydryl levels. Furthermore, the levels of oxidative stress probes/markers (i.e.,2′,7′-dichlorodihydrofluoresceindiacetateand nitrite) were higher in the LPS-treated rats. These effects were all reversed in the cortex and hippocampus by insulin treatment. Our results suggest a pot