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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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Related in: MedlinePlus

No acute and direct effect of laminarin on neuronal activity. A. Examples of intracellular recordings of CGCs before or after 30 minutes exposure of the isolated CNS to vehicle (saline) only (top trace) or laminarin (bottom trace). B. Average membrane potential of the CGCs before or 30 minutes post-treatment in vehicle only or laminarin exposed CNS. No significant difference was observed between the two treatment groups. C. Relative action potential frequency of CGCs 15 minutes before and during 30 minutes of exposure to laminarin or vehicle only. No significant difference was observed between the two treatment groups.
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Figure 2: No acute and direct effect of laminarin on neuronal activity. A. Examples of intracellular recordings of CGCs before or after 30 minutes exposure of the isolated CNS to vehicle (saline) only (top trace) or laminarin (bottom trace). B. Average membrane potential of the CGCs before or 30 minutes post-treatment in vehicle only or laminarin exposed CNS. No significant difference was observed between the two treatment groups. C. Relative action potential frequency of CGCs 15 minutes before and during 30 minutes of exposure to laminarin or vehicle only. No significant difference was observed between the two treatment groups.

Mentions: Next, we examined whether laminarin application to the nervous system directly affect neuronal activity of the cerebral giant cells (CGC), serotonergic modulatory interneurons with a critical function in the expression of appetitive LTM. CNSs were either exposed for 15 minutes to saline followed by a 30 min laminarin (5 mg/ml) treatment or to saline only for the same period of time while recording intracellular from the CGC. These experiments revealed no significant differences in CGC resting membrane potential and spontaneous action potential activity between CNS subjected to the two test conditions (Figure 2; ANOVA interaction time × treatment; F1,9 = 0.26, p = 0.62 for resting membrane potential and F8,36 = 0.44, p = 0.89 for electrical activity).


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)

No acute and direct effect of laminarin on neuronal activity. A. Examples of intracellular recordings of CGCs before or after 30 minutes exposure of the isolated CNS to vehicle (saline) only (top trace) or laminarin (bottom trace). B. Average membrane potential of the CGCs before or 30 minutes post-treatment in vehicle only or laminarin exposed CNS. No significant difference was observed between the two treatment groups. C. Relative action potential frequency of CGCs 15 minutes before and during 30 minutes of exposure to laminarin or vehicle only. No significant difference was observed between the two treatment groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: No acute and direct effect of laminarin on neuronal activity. A. Examples of intracellular recordings of CGCs before or after 30 minutes exposure of the isolated CNS to vehicle (saline) only (top trace) or laminarin (bottom trace). B. Average membrane potential of the CGCs before or 30 minutes post-treatment in vehicle only or laminarin exposed CNS. No significant difference was observed between the two treatment groups. C. Relative action potential frequency of CGCs 15 minutes before and during 30 minutes of exposure to laminarin or vehicle only. No significant difference was observed between the two treatment groups.
Mentions: Next, we examined whether laminarin application to the nervous system directly affect neuronal activity of the cerebral giant cells (CGC), serotonergic modulatory interneurons with a critical function in the expression of appetitive LTM. CNSs were either exposed for 15 minutes to saline followed by a 30 min laminarin (5 mg/ml) treatment or to saline only for the same period of time while recording intracellular from the CGC. These experiments revealed no significant differences in CGC resting membrane potential and spontaneous action potential activity between CNS subjected to the two test conditions (Figure 2; ANOVA interaction time × treatment; F1,9 = 0.26, p = 0.62 for resting membrane potential and F8,36 = 0.44, p = 0.89 for electrical activity).

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