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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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Effect of laminarin injection on chemosensory and motor function. A. Examples of extracellular recording of afferents in the superior lip nerve before and after application of n-amyl acetate (4 ppm) of animals injected one hour prior with vehicle only (top trace) or laminarin (bottom trace). B. Average action potential frequency (bin size 30 sec) of afferents in superior lip nerve 3 minutes before and 2 minutes during amyl acetate application. There is no difference in response upon n-amyl acetate application between the two different treatment groups C. Average change in the number of rasps evoked by application of pond water (DS) or sucrose (0.4%). Only sucrose induced a robust but similar response in animals injected with vehicle or laminarin.
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Figure 4: Effect of laminarin injection on chemosensory and motor function. A. Examples of extracellular recording of afferents in the superior lip nerve before and after application of n-amyl acetate (4 ppm) of animals injected one hour prior with vehicle only (top trace) or laminarin (bottom trace). B. Average action potential frequency (bin size 30 sec) of afferents in superior lip nerve 3 minutes before and 2 minutes during amyl acetate application. There is no difference in response upon n-amyl acetate application between the two different treatment groups C. Average change in the number of rasps evoked by application of pond water (DS) or sucrose (0.4%). Only sucrose induced a robust but similar response in animals injected with vehicle or laminarin.

Mentions: First, we verified the amyl-acetate detection ability of laminarin-treated animals through analysis of evoked electrical responses recorded in the right superior lip nerve (RSLN) of semi-intact preparations. The RSLN carries chemosensory information from the lip area to the CNS. Figures 4A and 4B show representative examples of extracellular recordings of the RSLN of animals pre-treated 1 hr prior with vehicle-only and laminarin injections. The figures illustrate that robust increases in spiking frequency were recorded from the RSLN upon application of 4 ppm amyl-acetate to the lip in both experimental groups. On average, spiking frequency rapidly climbed from a baseline of around 200 events per 30 seconds immediately preceding the sensory stimulus to 300-400 events per 30 seconds during application of the stimulus in both test groups (n = 8 for both groups). Formal statistical analysis indicated a highly significant effect of peripheral amyl-acetate application on RSLN spiking frequency that was independent of prior treatment of the test animals (ANOVA time vs. treatment F1,9 = 1.349, p = 0.22; laminarin amyl-acetate effect in laminarin pre-treated preparations F1,14 = 60.87, p < 0.0001; amyl-acetate effect in vehicle-only pre-treated preparations F1,14 = 15.871, p < 0.001).


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)

Effect of laminarin injection on chemosensory and motor function. A. Examples of extracellular recording of afferents in the superior lip nerve before and after application of n-amyl acetate (4 ppm) of animals injected one hour prior with vehicle only (top trace) or laminarin (bottom trace). B. Average action potential frequency (bin size 30 sec) of afferents in superior lip nerve 3 minutes before and 2 minutes during amyl acetate application. There is no difference in response upon n-amyl acetate application between the two different treatment groups C. Average change in the number of rasps evoked by application of pond water (DS) or sucrose (0.4%). Only sucrose induced a robust but similar response in animals injected with vehicle or laminarin.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Effect of laminarin injection on chemosensory and motor function. A. Examples of extracellular recording of afferents in the superior lip nerve before and after application of n-amyl acetate (4 ppm) of animals injected one hour prior with vehicle only (top trace) or laminarin (bottom trace). B. Average action potential frequency (bin size 30 sec) of afferents in superior lip nerve 3 minutes before and 2 minutes during amyl acetate application. There is no difference in response upon n-amyl acetate application between the two different treatment groups C. Average change in the number of rasps evoked by application of pond water (DS) or sucrose (0.4%). Only sucrose induced a robust but similar response in animals injected with vehicle or laminarin.
Mentions: First, we verified the amyl-acetate detection ability of laminarin-treated animals through analysis of evoked electrical responses recorded in the right superior lip nerve (RSLN) of semi-intact preparations. The RSLN carries chemosensory information from the lip area to the CNS. Figures 4A and 4B show representative examples of extracellular recordings of the RSLN of animals pre-treated 1 hr prior with vehicle-only and laminarin injections. The figures illustrate that robust increases in spiking frequency were recorded from the RSLN upon application of 4 ppm amyl-acetate to the lip in both experimental groups. On average, spiking frequency rapidly climbed from a baseline of around 200 events per 30 seconds immediately preceding the sensory stimulus to 300-400 events per 30 seconds during application of the stimulus in both test groups (n = 8 for both groups). Formal statistical analysis indicated a highly significant effect of peripheral amyl-acetate application on RSLN spiking frequency that was independent of prior treatment of the test animals (ANOVA time vs. treatment F1,9 = 1.349, p = 0.22; laminarin amyl-acetate effect in laminarin pre-treated preparations F1,14 = 60.87, p < 0.0001; amyl-acetate effect in vehicle-only pre-treated preparations F1,14 = 15.871, p < 0.001).

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