Abstract
By employing a reductionistic (but not simplistic) approach using an established invertebrate model system, the pond snail Lymnaea stagnalis, we investigated whether (1) lipopolysaccharide (LPS)-induced inflammation would cause a sickness state and impair cognitive function, and—if so—(2) would aspirin (acetylsalicylic acid—ASA) restore the impaired cognition. To test our hypotheses, we first determined if the injection of 25 mg (6.25 μg/mL) of Escherichia coli-derived LPS serotype O127:B8 altered homeostatic behavior, aerial respiration, and then determined if LPS altered memory formation when this behavior was operantly conditioned. Next, we determined if ASA altered the LPS-induced changes in both aerial respiration and cognitive functions. LPS induced a sickness state that increased aerial respiration and altered the ability of snails to form or recall long-term memory. ASA reverted the LPS-induced sickness state and thus allowed long-term memory both to be formed and recalled. We confirmed our hypotheses and provided the first evidence in an invertebrate model system that an injection of LPS results in a sickness state that obstructs learning and memory, and this impairment can be prevented by a non-steroidal anti-inflammatory.
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Funding
The current work was funded by the Natural Sciences and Engineering Research Council of Canada and Regione Emilia-Romagna L.R. N. 20/2002 PROGETTI DI RICERCA SUI METODI ALTERNATIVI ALL’UTILIZZO DI ANIMALI; and FAR 2016 Department of Life Sciences, University of Modena and Reggio Emilia
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All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Veronica Rivi. Ken Lukowiak supervised the findings of this work, and all authors discussed the results. The first draft of the manuscript was written by Veronica Rivi with support from Anuradha Batabyal and Cristina Benatti. All authors commented on previous versions of the manuscript and approved the final manuscript. Acquisition of the financial support for the project leading to this publication were provided by Ken Lukowiak and Fabio Tascedda.
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Ethical approval is not required for research work with L. stagnalis; however, every effort was made to ameliorate suffering of animals, ensuring adequate food, clean oxygenated water, and low-density housing conditions. The LPS treatment used in this study has no long-term effects on the animals (personal observations). The collection of L. stagnalis for this study did not involve endangered or protected species and specific permits were required for the described field collections.
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Rivi, V., Batabyal, A., Benatti, C. et al. Aspirin reverts lipopolysaccharide-induced learning and memory impairment: first evidence from an invertebrate model system. Naunyn-Schmiedeberg's Arch Pharmacol 395, 1573–1585 (2022). https://doi.org/10.1007/s00210-022-02286-4
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DOI: https://doi.org/10.1007/s00210-022-02286-4