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Lithium activates brain phospholipase A2 and improves memory in rats: implications for Alzheimer’s disease

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Abstract

Phospholipase A2 (Pla2) is required for memory retrieval, and its inhibition in the hippocampus has been reported to impair memory acquisition in rats. Moreover, cognitive decline and memory deficits showed to be reduced in animal models after lithium treatment, prompting us to evaluate possible links between Pla2, lithium and memory. Here, we evaluated the possible modulation of Pla2 activity by a long-term treatment of rats with low doses of lithium and its impact in memory. Wistar rats were trained for the inhibitory avoidance task, treated with lithium for 100 days and tested for perdurability of long-term memory. Hippocampal samples were used for quantifying the expression of 19 brain-expressed Pla2 genes and for evaluating the enzymatic activity of Pla2 using group-specific radio-enzymatic assays. Our data pointed to a significant perdurability of long-term memory, which correlated with increased transcriptional and enzymatic activities of certain members of the Pla2 family (iPla2 and sPla2) after the chronic lithium treatment. Our data suggest new possible targets of lithium, add more information on its pharmacological activity and reinforce the possible use of low doses of lithium for the treatment of neurodegenerative conditions such as the Alzheimer’s disease.

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Acknowledgments

The authors acknowledge the support received from Associação Beneficente Alzira Denise Hertzog da Silva (ABADHS), Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP; Grants 04/02165-8, 04/01478-2, 09/52825-8). ED-N is a research fellow from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). WFG acknowledges the support of JNK Empreendimentos e Incorporações given to the Laboratory of Neurosciences (LIM-27). The authors thank Dr. Gustavo Ribeiro Fernandes for his help with data analysis.

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    1. Laboratório de Neurociências (LIM27), Instituto de Psiquiatria, Faculdade de Medicina da Universidade de São Paulo, Rua Ovídio Pires de Campos, 785, 05403-010, São Paulo, SP, Brazil

      Fábio B. Mury, Nádia R. Barbosa, Camila T. Mendes, Wagner F. Gattaz & Emmanuel Dias-Neto

    2. Pós-Graduação Interunidades em Biotecnologia, Universidade de São Paulo, São Paulo, SP, Brazil

      Fábio B. Mury & Camila T. Mendes

    3. Centro de Memória, Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil

      Weber C. da Silva, Juliana S. Bonini & Ivan Izquierdo

    4. Instituto de Pesquisas Energéticas e Nucleares-IPEN-CNEN/SP, Grupo de Caracterização Química e Isotópica, Universidade de São Paulo, São Paulo, SP, Brazil

      Jorge Eduardo Souza Sarkis

    5. Laboratório de Pesquisa de Memória, Instituto do Cérebro, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil

      Martin Cammarota

    6. Departamento de Farmácia, Universidade Estadual do Centro-Oeste, Guarapuava, PR, Brazil

      Weber C. da Silva & Juliana S. Bonini

    7. Laboratório de Genômica Médica, Centro Internacional de Pesquisas, AC Camargo Cancer Center, São Paulo, SP, Brazil

      Emmanuel Dias-Neto

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    Fábio B. Mury and Weber C. da Silva have contributed equally to this work.

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    Mury, F.B., da Silva, W.C., Barbosa, N.R. et al. Lithium activates brain phospholipase A2 and improves memory in rats: implications for Alzheimer’s disease. Eur Arch Psychiatry Clin Neurosci 266, 607–618 (2016). https://doi.org/10.1007/s00406-015-0665-2

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