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Diabetes affects the morphology and plasticity of the hippocampus, and leads to learning and memory deficits. Caffeine has been proposed to prevent memory impairment upon multiple chronic disorders with neurological involvement. We tested whether long-term caffeine consumption prevents type 2 diabetes (T2D)-induced spatial memory impairment and hippocampal alterations, including synaptic degeneration, astrogliosis, and metabolic modifications. Control Wistar rats and Goto-Kakizaki (GK) rats that develop T2D were treated with caffeine (1 g/L in drinking water) for 4 months. Spatial memory was evaluated in a Y-maze. Hippocampal metabolic profile and glucose homeostasis were investigated by  1 H magnetic resonance spectroscopy. The density of neuronal, synaptic, and glial-specific markers was evaluated by Western blot analysis. GK rats displayed reduced Y-maze spontaneous alternation and a lower amplitude of hippocampal long-term potentiation when compared to controls, suggesting impaired hippocampal-dependent spatial memory. Diabetes did not impact the relation of hippocampal to plasma glucose concentrations, but altered the neurochemical profile of the hippocampus, such as increased in levels of the osmolites taurine ( P  < 0.001) and  myo -inositol ( P  < 0.05). The diabetic hippocampus showed decreased density of the presynaptic proteins synaptophysin ( P  < 0.05) and SNAP25 ( P  < 0.05), suggesting synaptic degeneration, and increased GFAP ( P  < 0.001) and vimentin ( P  < 0.05) immunoreactivities that are indicative of astrogliosis. The effects of caffeine intake on hippocampal metabolism added to those of T2D, namely reducing  myo -inositol levels ( P  < 0.001) and further increasing taurine levels ( P  < 0.05). Caffeine prevented T2D-induced alterations of GFAP, vimentin and SNAP25, and improved memory deficits. We conclude that caffeine consumption has beneficial effects counteracting alterations in the hippocampus of GK rats, leading to the improvement of T2D-associated memory impairment.

Impact of Caffeine Consumption on Type 2 Diabetes-Induced Spatial Memory Impairment and Neurochemical Alterations in the Hippocampus