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

Hermann PM, Park D, Beaulieu E, Wildering WC - BMC Neurosci (2013)

Bottom Line: 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.This effect dissipated within 24 hrs after treatment.Our findings underwrite the rapidly expanding view of neuroinflammatory processes as a fundamental, evolutionary conserved cause of cognitive and other nervous system disorders.

View Article: PubMed Central - HTML - PubMed

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

ABSTRACT

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 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.

Results: 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.

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 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.

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Time dependent effect of laminarin induced release of H2O2 by haemocytes. An increase in H2O2 production was detected when animals received a bolus injection of laminarin 3 hrs before hemocyte collection in comparison with their time corresponding vehicle treated animals. Injection of laminarin 0.5 hr, 1 hr or 24 hrs before measurement failed to detect any differences in H2O2 release between the laminarin treated groups and their time corresponding vehicle treated animals. * = p < 0.05.
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Figure 1: Time dependent effect of laminarin induced release of H2O2 by haemocytes. An increase in H2O2 production was detected when animals received a bolus injection of laminarin 3 hrs before hemocyte collection in comparison with their time corresponding vehicle treated animals. Injection of laminarin 0.5 hr, 1 hr or 24 hrs before measurement failed to detect any differences in H2O2 release between the laminarin treated groups and their time corresponding vehicle treated animals. * = p < 0.05.

Mentions: 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. Haemocytes of both laminarin-treated and vehicle control animals were collected 0.5, 1, 3 and 24 hrs after injection and immediately submitted to fluorescent respiratory burst assays. Figure 1 shows that Amplex-Red fluorescence was very similar in samples of haemocytes collected from laminarin and vehicle treated animals 0.5 hr, 1 hr and 24 hrs after injection, but significantly differed in samples collected 3 hrs after injection (Figure 1; ANOVA interaction time × treatment; F3,82 = 3.04, p < 0.05 planned comparison laminarin vs. vehicle at 0.5 hr F1,82 = 0.578, p = 0.45; 1 hr F1,82 = 0.549, p = 0.46; 3 hrs F1,82 = 8.177, p = 0.005; 24 hrs F1,82 = 0.027, p = 0.86).


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

Hermann PM, Park D, Beaulieu E, Wildering WC - BMC Neurosci (2013)

Time dependent effect of laminarin induced release of H2O2 by haemocytes. An increase in H2O2 production was detected when animals received a bolus injection of laminarin 3 hrs before hemocyte collection in comparison with their time corresponding vehicle treated animals. Injection of laminarin 0.5 hr, 1 hr or 24 hrs before measurement failed to detect any differences in H2O2 release between the laminarin treated groups and their time corresponding vehicle treated animals. * = p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750374&req=5

Figure 1: Time dependent effect of laminarin induced release of H2O2 by haemocytes. An increase in H2O2 production was detected when animals received a bolus injection of laminarin 3 hrs before hemocyte collection in comparison with their time corresponding vehicle treated animals. Injection of laminarin 0.5 hr, 1 hr or 24 hrs before measurement failed to detect any differences in H2O2 release between the laminarin treated groups and their time corresponding vehicle treated animals. * = p < 0.05.
Mentions: 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. Haemocytes of both laminarin-treated and vehicle control animals were collected 0.5, 1, 3 and 24 hrs after injection and immediately submitted to fluorescent respiratory burst assays. Figure 1 shows that Amplex-Red fluorescence was very similar in samples of haemocytes collected from laminarin and vehicle treated animals 0.5 hr, 1 hr and 24 hrs after injection, but significantly differed in samples collected 3 hrs after injection (Figure 1; ANOVA interaction time × treatment; F3,82 = 3.04, p < 0.05 planned comparison laminarin vs. vehicle at 0.5 hr F1,82 = 0.578, p = 0.45; 1 hr F1,82 = 0.549, p = 0.46; 3 hrs F1,82 = 8.177, p = 0.005; 24 hrs F1,82 = 0.027, p = 0.86).

Bottom Line: 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.This effect dissipated within 24 hrs after treatment.Our findings underwrite the rapidly expanding view of neuroinflammatory processes as a fundamental, evolutionary conserved cause of cognitive and other nervous system disorders.

View Article: PubMed Central - HTML - PubMed

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

ABSTRACT

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 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.

Results: 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.

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 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.

Show MeSH
Related in: MedlinePlus