Abstract
Background: Diabetes mellitus is a metabolic disease which also causes cognitive deficits. Betaine (N,N,N-trimethylglycine), also known as trimethylglycine, has been shown to ameliorate diabetic symptoms in diabetic animals and improve cognitive ability in Alzheimer disease (AD) animals. However, the effects of betaine on cognitive deficits in diabetic animals have not been described yet. Therefore, in the current study, the effects of betaine on cognition in diabetic rats were evaluated. Methods: We established a diabetic rat model by injecting streptozotocin (STZ) into rats and administrated betaine to these diabetic rats. We monitored the metabolism index, and glucose and insulin levels in blood and cerebrospinal fluid. We measured inflammatory cytokine levels, including TNF-α, IL-1β, and IL-6, in serum and hippocampus. We also monitored oxidative stress in the hippocampus by measuring malondialdehyde (MDA) level and superoxide dismutase (SOD) activity. We measured the learning and memory ability of diabetic rats using the Morris water and Y maze tests and tested the phosphatidylinositol 3-kinase (PI3K)/Akt activation and p-mTOR level in the hippocampus. Results: Betaine improved glucose metabolism and suppressed the production of inflammatory cytokines, including TNF-α, IL-1β, and IL-6. Also, betaine decreased MDA concentration and increased SOD activity in the hippocampus of diabetic rats. Betaine ameliorated cognitive deficits in diabetic rats, and it promoted PI3K expression and Akt activation and decreased p-mTOR expression. Conclusion: Betaine alleviates cognitive deficits in STZ-induced diabetic rats via regulating the PI3K/Akt signaling pathway.
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