The Anxiolytic Effect of Alpha-Linoleic Acid in Alzheimer's Disease Model Rats is Mediated by Enhanced Brain-Derived Neurotrophic Factor Expression

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.

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.

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).

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.