Abstract
BackgroundPrevious studies associate lipid peroxidation with long-term memory (LTM) failure in a gastropod model (Lymnaea stagnalis) of associative learning and memory. This process involves activation of Phospholipase A2 (PLA2), an enzyme mediating the release of fatty acids such as arachidonic acid that form the precursor for a variety of pro-inflammatory lipid metabolites. This study investigated the effect of biologically realistic challenges of L. stagnalis host defense response system on LTM function and potential involvement of PLA2, COX and LOX therein.ResultsSystemic immune challenges by means of β-glucan laminarin injections induced elevated H2O2 release from L. stagnalis circulatory immune cells within 3 hrs of treatment. This effect dissipated within 24 hrs after treatment. Laminarin exposure has no direct effect on neuronal activity. Laminarin injections disrupted LTM formation if training followed within 1 hr after injection but had no behavioural impact if training started 24 hrs after treatment. Intermediate term memory was not affected by laminarin injection. Chemosensory and motor functions underpinning the feeding response involved in this learning model were not affected by laminarin injection. Laminarin’s suppression of LTM induction was reversed by treatment with aristolochic acid, a PLA2 inhibitor, or indomethacin, a putative COX inhibitor, but not by treatment with nordihydro-guaiaretic acid, a putative LOX inhibitor.ConclusionsA systemic immune challenge administered shortly before behavioural training impairs associative LTM function in our model that can be countered with putative inhibitors of PLA2 and COX, but not LOX. As such, this study establishes a mechanistic link between the state of activity of this gastropod’s innate immune system and higher order nervous system function. Our findings underwrite the rapidly expanding view of neuroinflammatory processes as a fundamental, evolutionary conserved cause of cognitive and other nervous system disorders.
Highlights
Previous studies associate lipid peroxidation with long-term memory (LTM) failure in a gastropod model (Lymnaea stagnalis) of associative learning and memory
One of the major players in the execution of the inflammatory response recruited by Reactive oxygen species (ROS) is Phospholipase A2 (PLA2), a family of enzymes that mediate the release of free fatty acids (FFA) from the sn-2 position of membrane phospholipids [9,10,11,12]
In vivo immune response to laminarin To examine whether systemic delivery of a immune stimulant triggers an immune response in animals, we first performed experiments measuring haemocyte H2O2 release at varying times after intracoelomic injection of a single bolus of laminarin (~5 mg/ml haemolymph concentration) or vehicle-only
Summary
Previous studies associate lipid peroxidation with long-term memory (LTM) failure in a gastropod model (Lymnaea stagnalis) of associative learning and memory This process involves activation of Phospholipase A2 (PLA2), an enzyme mediating the release of fatty acids such as arachidonic acid that form the precursor for a variety of pro-inflammatory lipid metabolites. Its activation is characterized by a host of cellular responses including the release of pro-inflammatory compounds such as cytokines and the production of high levels of reactive oxygen and nitrogen species (ROS and RNS) [1,2,3] While these compounds play critical roles in the orchestration and execution of the host defense response, their actions are not always limited to the immune system. ROS are generated as a by-product of COX activity, creating a positive feedback loop that potentially can cause escalation of PLA2 and COXdependent aspects of the host defense response and substantive deregulation of lipid homeostasis [15,19]
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