Abstract
BackgroundReactive oxygen species (ROS) are essential for normal physiological functioning of the brain. However, uncompensated increase in ROS levels may results in oxidative stress. Phospholipase A2 (PLA2) is one of the key players activated by elevated ROS levels resulting in the hydrolysis of various products from the plasmamembrane such as peroxidized fatty acids. Free fatty acids (FFAs) and fatty acid metabolites are often implicated to the genesis of cognitive impairment. Previously we have shown that age-, and experimentally induced oxidative stress causes PLA2-dependent long-term memory (LTM) failure in an aversive operant conditioning model in Lymnaea stagnalis. In the present study, we investigate the effects of experimentally induced oxidative stress and the role of elevated levels of circulating FFAs on LTM function using a non-aversive appetitive classical conditioning paradigm.ResultsWe show that intracoelomic injection of exogenous PLA2 or pro-oxidant induced PLA2 activation negatively affects LTM performance in our learning paradigm. In addition, we show that experimental induction of oxidative stress causes significant temporal changes in circulating FFA levels. Importantly, the time of training coincides with the peak of this change in lipid metabolism. However, intracoelomic injection with exogenous arachidonic acid, one of the main FFAs released by PLA2, does not affect LTM function. Moreover, sequestrating circulating FFAs with the aid of bovine serum albumin does not rescue pro-oxidant induced appetitive LTM failure.ConclusionsOur data substantiates previous evidence linking lipid peroxidation and PLA2 activation to age- and oxidative stress-related cognitive impairment, neuronal dysfunction and disease. In addition however, our data indicate that lipid peroxidation induced increased levels of circulating (per)oxidized FFAs are not a factor in oxidative stress induced LTM impairment.
Highlights
Reactive oxygen species (ROS) are essential for normal physiological functioning of the brain
We utilized an established and widely studied classical appetitive rewardconditioning paradigm involving chemosensory conditioning of the animals’ feeding behaviour i.e., “rasping” [22,24,25,26,27]. Using this model we investigated the effects of experimentally pro-oxidant induced Phospholipase A2 (PLA2) activation on associative appetitive long-term memory (LTM) impairment and the role of circulating free fatty acid (FFA) therein
Enhanced levels of extracellular PLA2 inhibit LTM formation To assess the impact of increased levels of extracellular PLA2 on the formation of appetitive LTM, animals randomly assigned to two test groups were injected with PLA2 from bee venom or vehicle-only 1 hr before their first training session
Summary
Reactive oxygen species (ROS) are essential for normal physiological functioning of the brain. Phospholipase A2 (PLA2) is one of the key players activated by elevated ROS levels resulting in the hydrolysis of various products from the plasmamembrane such as peroxidized fatty acids. We investigate the effects of experimentally induced oxidative stress and the role of elevated levels of circulating FFAs on LTM function using a non-aversive appetitive classical conditioning paradigm. High levels of ROS are shown to cause detrimental effects in the brain that negatively affect neuronal plasticity and memory function [3,4]. Under normal physiological conditions PLA2, its products and their metabolites play essential roles in regulating signal transduction, various neuronal signaling pathways, ion channel functioning and gene transcription processes [15,17,18,19,20,21]. The physiological mechanisms underlying these phenomena remain incompletely resolved
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