Preventive Effect of Betaine Against Cognitive Impairments in Amyloid β Peptide-Injected Mice Through Sirtuin1 in Hippocampus

In the pathophysiology of Alzheimer's disease, the deposition of amyloid beta peptide (A beta) is associated with oxidative stress, leading to cognitive impairment and neurodegeneration. We have already reported that betaine (glycine betaine), an osmolyte and methyl donor in cells, prevents the development of cognitive impairment in mice with intracerebroventricular injection of A beta(25-35), an active fragment of A beta, associated with oxidative stress in the hippocampus, but molecular mechanisms of betaine remain to be determined. Here, to investigate a key molecule underlying the preventive effect of betaine against cognitive impairments in A beta(25-35)-injected mice, cognitive tests and qPCR assays were performed in A beta(25-35)-injected mice with continuous betaine intake, in which intake was started a day before A beta(25-35) injection, and then continued for 8 days. The A beta(25-35) injection impaired short-term and object recognition memories in the Y-maze and object recognition tests, respectively. PCR assays revealed the down-regulation of Sirtuin1 (SIRT1), a NAD(+)-dependent deacetylase that mediates metabolic responses, in the hippocampus of A beta(25-35)-injected mice, whereas betaine intake prevented memory deficits as well as the decrease of hippocampal SIRT1 expression in A beta(25-35)-injected mice. Further, sirtinol, an inhibitor of the Sirtuin family, blocked the preventive effect of betaine against memory deficits. On the other hand, resveratrol, the potent compound that activates SIRT1, also prevented memory impairments in A beta(25-35)-injected mice, suggesting that SIRT1 plays a causative role in the preventive effect of betaine against memory deficits caused by A beta exposure.

Automated summary

This study found that betaine can prevent memory impairments caused by Aβ deposition and its mechanism of action involves activating the SIRT1 molecule. These findings provide new insight for the treatment of Alzheimer's disease.