In the pathophysiology of Alzheimer's disease, the deposition of amyloid β peptide (Aβ) 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 Aβ25-35, an active fragment of Aβ, 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 Aβ25-35-injected mice, cognitive tests and qPCR assays were performed in Aβ25-35-injected mice with continuous betaine intake, in which intake was started a day before Aβ25-35 injection, and then continued for 8 days. The Aβ25-35 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 Aβ25-35-injected mice, whereas betaine intake prevented memory deficits as well as the decrease of hippocampal SIRT1 expression in Aβ25-35-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 Aβ25-35-injected mice, suggesting that SIRT1 plays a causative role in the preventive effect of betaine against memory deficits caused by Aβ exposure.
Keywords: Alzheimer’s disease; Amyloid β protein; Betaine; Sirtuin.
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.