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Background  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 A 2  (PLA 2 ), 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 PLA 2 , COX and LOX therein.    Results  Systemic immune challenges by means of β-glucan laminarin injections induced elevated H 2 O 2  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 PLA 2  inhibitor, or indomethacin, a putative COX inhibitor, but not by treatment with nordihydro-guaiaretic acid, a putative LOX inhibitor.    Conclusions  A systemic immune challenge administered shortly before behavioural training impairs associative LTM function in our model that can be countered with putative inhibitors of PLA 2  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.

bmc neuroscience

Evidence for inflammation-mediated memory dysfunction in gastropods: putative PLA2and COX inhibitors abolish long-term memory failure induced by systemic immune challenges