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

  • Fábio B. Mury
  • Weber C. da Silva
  • Nádia R. Barbosa
  • Camila T. Mendes
  • Juliana S. Bonini
  • Jorge Eduardo Souza Sarkis
  • Martin Cammarota
  • Ivan Izquierdo
  • Wagner F. Gattaz
  • Emmanuel Dias-Neto
Original Paper


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.


Lithium Memory PLA2 Step-down inhibitory avoidance task Hippocampus Gene expression 



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.

Compliance with ethical standards

Conflict of interest


Supplementary material

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Supplementary material 1 (DOC 1621 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Fábio B. Mury
    • 1
    • 2
  • Weber C. da Silva
    • 3
    • 6
  • Nádia R. Barbosa
    • 1
  • Camila T. Mendes
    • 1
    • 2
  • Juliana S. Bonini
    • 3
    • 6
  • Jorge Eduardo Souza Sarkis
    • 4
  • Martin Cammarota
    • 5
  • Ivan Izquierdo
    • 3
  • Wagner F. Gattaz
    • 1
  • Emmanuel Dias-Neto
    • 1
    • 7
  1. 1.Laboratório de Neurociências (LIM27), Instituto de PsiquiatriaFaculdade de Medicina da Universidade de São PauloSão PauloBrazil
  2. 2.Pós-Graduação Interunidades em BiotecnologiaUniversidade de São PauloSão PauloBrazil
  3. 3.Centro de Memória, Instituto de Pesquisas BiomédicasPontifícia Universidade Católica do Rio Grande do SulPorto AlegreBrazil
  4. 4.Instituto de Pesquisas Energéticas e Nucleares-IPEN-CNEN/SP, Grupo de Caracterização Química e IsotópicaUniversidade de São PauloSão PauloBrazil
  5. 5.Laboratório de Pesquisa de Memória, Instituto do CérebroUniversidade Federal do Rio Grande do NorteNatalBrazil
  6. 6.Departamento de FarmáciaUniversidade Estadual do Centro-OesteGuarapuavaBrazil
  7. 7.Laboratório de Genômica MédicaCentro Internacional de Pesquisas, AC Camargo Cancer CenterSão PauloBrazil

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