Protective effect of alpha-linoleic acid on A beta-induced oxidative stress, neuroinflammation, and memory impairment by alteration of alpha 7 nAChR and NMDAR gene expression in the hippocampus of rats

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects many older people around the world. Numerous studies are underway to evaluate the protective effects of natural products in AD. Alphalinoleic acid (ALA) is an essential unsaturated fatty acid that exhibits neuroprotective outcomes in rat models of ischemic stroke and Parkinson's disease. This research aimed to investigate the effect of ALA on oxidative stress, neuroinflammation, neuronal death, and memory deficit induced by amyloid-beta (A beta) peptide. After intrahippocampal injection of A beta(1-42), rats received ALA (150 mu g/kg, subcutaneously) for 14 consecutive days. ALA decreased the levels of malondialdehyde and nitric oxide, enhanced glutathione content, and increased the activity of catalase in the hippocampus of the rat model of AD. It also reduced the expression of tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, nuclear factor-kappa B, and N-methyl-D-aspartate receptor subunits NR2A and NR2B mRNAs in the hippocampus, prevented the neuronal loss in the CA1 region, and enhanced the expression of alpha 7 nicotinic acetylcholine receptor. In addition, ALA allowed A beta(1-42)-injected rats to spend less time and distance to reach the hidden platform in the Morris water maze test and to swim longer in the target quadrant. We concluded that ALA reduces the biochemical, molecular, histological, and behavioral changes caused by A beta(1-42) and it may be an effective option for treating AD.