The anxiolytic effect of alpha-linoleic acid in Alzheimer's disease model rats is mediated by enhanced brain-derived neurotrophic factor expression

Abstract

Introduction: The deposition of amyloid beta peptide (Aβ) in the brain is one of the hallmarks of Alzheimer's disease. In addition to inducing oxidative stress and inflammation, beta-amyloid reduces the expression of brain-derived neurotropic factor (BDNF) and causes behavioral disorders such as anxiety even before memory impairment. Alpha-linoleic acid is an omega-3 unsaturated fatty acid that has antioxidant, anti-inflammatory, and neuroprotective effects. This study aimed to investigate the effect of alpha-linoleic acid on anxiety induced by Aβ1-42 and examined the possible role of BDNF in this effect.

Methods: Male Wistar rats were divided into four groups included control, alpha-linoleic acid, Aβ, and Aβ-alpha-linoleic acid. After intra-hippocampal injection of Aβ1-42, the animals received alpha-linoleic acid subcutaneously at a dose of 150 μg/kg. At the end of the course, the anxious behavior of the animals was assessed using an elevated plus-plus maze test and BDNF mRNA expression in the hippocampus was measured by real-time PCR. The significant level was set at 0.05.

Results: In the elevated plus-maze test, alpha-linoleic acid significantly increased the percentage of open arm entry and the percentage of time spent in open arm in rats receiving Aβ1-42 (P<0.001). Alpha-linoleic acid also increased BDNF mRNA expression in the hippocampus of these animals (P<0.05).

Conclusion: Based on the results of the study, alpha-linoleic acid has an anxiolytic effect in Alzheimer's disease model rats, and this effect is largely exerted by an increase in BDNF. Alpha-linoleic acid may be effective in reducing neurodegeneration.