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Inhibition of calcium-independent phospholipase A2 activity in rat hippocampus impairs acquisition of short- and long-term memory

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Abstract

Rationale

Phospholipase A2 (PLA2) is a family of enzymes that cleave membrane phospholipids generating important lipid mediators in signal transduction. In rat hippocampal slices, both intracellular cytosolic Ca2+-dependent PLA2 (cPLA2) and Ca2+-independent PLA2 (iPLA2) have been implicated in mechanisms of synaptic plasticity underlying memory processes. In mice, intraperitoneal injections of a selective iPLA2 inhibitor impaired spatial learning. Accordingly, reduced cPLA2 and iPLA2 activities were found in postmortem hippocampus of patients with Alzheimer’s disease.

Objective

This study investigates the effects of injections of PLA2 inhibitors directly into rat hippocampus on the acquisition of short-term (STM) and long-term memory (LTM) of a one-trial step-down inhibitory avoidance (IA) task.

Methods

Wistar rats were bilaterally implanted with cannulae in the CA1 region of the dorsal hippocampus. After surgery, the rats received bilateral injections of a vehicle, or of dual cPLA2 and iPLA2 inhibitors (MAFP or PACOCF3), or a selective iPLA2 inhibitor (bromoenol lactone) before training in IA. The animals were tested 1.5 h (for STM) and 24 h (for LTM) after training.

Results

Significant inhibition of iPLA2 activity in rat hippocampus impaired acquisition of STM and LTM. Memory impairment did not result from neuronal death after iPLA2 inhibition. Moreover, IA training per se increased significantly hippocampal PLA2 activity.

Conclusion

The present results suggest a functional effect of hippocampal PLA2 on the neurochemistry of memory acquisition and support the hypothesis that reduced PLA2 activity may contribute to memory impairment in Alzheimer’s disease.

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Acknowledgements

The present study was financially supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP; Projects 97/11083-0, 00/05288-2, 00/14528-7) and by Pfizer Laboratories Brazil. The Laboratory of Neuroscience receives financial support from the Associação Beneficente Alzira Denise Hertzog da Silva (ABADHS). We acknowledge the technical help of F. Bassi Jr., L.A. Jardim, and I.A. Zainaghi in some of the experiments.

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  1. Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Rua Dr. Ovídio Pires de Campos 785, 05403-010, São Paulo, SP, Brazil

    Evelin L. Schaeffer & Wagner F. Gattaz

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  1. Evelin L. Schaeffer
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  2. Wagner F. Gattaz
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Correspondence to Wagner F. Gattaz.

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Schaeffer, E.L., Gattaz, W.F. Inhibition of calcium-independent phospholipase A2 activity in rat hippocampus impairs acquisition of short- and long-term memory. Psychopharmacology 181, 392–400 (2005). https://doi.org/10.1007/s00213-005-2256-9

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  • DOI: https://doi.org/10.1007/s00213-005-2256-9

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