Involvement of GAT2/BGT-1 in the preventive effects of betaine on cognitive impairment and brain oxidative stress in amyloid β peptide-injected mice.

Abstract

In the pathophysiology of Alzheimer's disease (AD), the deposition of amyloid β protein (Aβ) 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 Aβ25-35, an active fragment of Aβ. Betaine prevented cognitive impairment as well as increases of the cortical and hippocampal MDA levels in Aβ25-35-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 Aβ25-35-induced cognitive impairment without affecting the increased MDA levels in the brain of Aβ25-35-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 Aβ25-35-injected mice, but GAT2/BGT-1 function is not required for the antioxidant effects of betaine.

• Authors: Daisuke Ibi, Azumi Tsuchihashi, Tomohiro Nomura, Masayuki Hiramatsu
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 842 Pg. 57-63 (Jan 05 2019) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 30393201 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• GABA Plasma Membrane Transport Proteins
• Neuroprotective Agents
• Peptide Fragments
• Slc6a12 protein, mouse
• amyloid beta-protein (25-35)
• Betaine
• Malondialdehyde

Topics

• Amyloid beta-Peptides (toxicity)
• Animals
• Betaine (pharmacology)
• Brain (drug effects, metabolism, physiopathology)
• Cognitive Dysfunction (chemically induced, metabolism, physiopathology, prevention & control)
• GABA Plasma Membrane Transport Proteins (metabolism)
• Injections
• Male
• Malondialdehyde (metabolism)
• Mice
• Neuroprotective Agents (pharmacology)
• Oxidative Stress (drug effects)
• Peptide Fragments (toxicity)
• Recognition, Psychology (drug effects, physiology)