Open Access Highly Accessed Open Badges Research article

Evidence for inflammation-mediated memory dysfunction in gastropods: putative PLA2 and COX inhibitors abolish long-term memory failure induced by systemic immune challenges

Petra M Hermann1, Deborah Park1, Emily Beaulieu1 and Willem C Wildering12*

Author affiliations

1 Department of Biological Sciences, Faculty of Science, University of Calgary, Calgary, AB T2N 1N4, Canada

2 Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada

For all author emails, please log on.

Citation and License

BMC Neuroscience 2013, 14:83  doi:10.1186/1471-2202-14-83

Published: 6 August 2013



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. 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.


Systemic 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.


A 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.

Oxidative stress; Mollusc; Classical conditioning; Laminarin; Phospholipase A2; Lipid peroxidation; Eicosanoid; Lymnaea stagnalis; Inflammation; Cyclooxygenase