ABSTRACT
In the pathophysiology of Alzheimer's disease (AD), the deposition of amyloid ß protein (Aß) is associated with oxidative stress, leading to cognitive impairment and neurodegeneration. Betaine (glycine betaine or trimethylglycine), known as an osmolyte and methyl donor in mammalian cells, has been reported to suppress the proinflammatory response and oxidative stress in the kidneys, but the effects of betaine on brain diseases remain to be determined. Here, to investigate the effects of betaine treatment on cognitive impairment and the increase in oxidative stress in the brain of an AD animal model, we performed a novel object recognition test and measured the malondialdehyde (MDA; a marker of oxidative stress) levels in the frontal cortex and hippocampus of mice intracerebroventricularly injected with Aß25-35, an active fragment of Aß. Betaine prevented cognitive impairment as well as increases of the cortical and hippocampal MDA levels in Aß25-35-injected mice. Of note, NNC 05-2090, a selective inhibitor of betaine/GABA transporter-1 (GAT2/BGT-1), reduced the preventive effects of betaine on Aß25-35-induced cognitive impairment without affecting the increased MDA levels in the brain of Aß25-35-injected mice. As betaine is used as a substrate of GAT2/BGT-1, these results suggest that betaine is transported through GAT2/BGT-1 and prevents cognitive impairment in Aß25-35-injected mice, but GAT2/BGT-1 function is not required for the antioxidant effects of betaine.
