Lithium activates brain phospholipase A2 and improves memory in rats: implications for Alzheimer’s disease
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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.
KeywordsLithium 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.
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Conflict of interest
- 18.Rockenstein E, Torrance M, Adame A, Mante M et al (2007) Neuroprotective effects of regulators of the glycogen synthase kinase-3 beta signaling pathway in a transgenic model of Alzheimer’s disease are associated with reduced amyloid precursor protein phosphorylation. J Neurosci 27:1981–1991CrossRefPubMedGoogle Scholar
- 44.Olfert ED (1993) Guide to the care and use of experimental animals, 2nd edn. Canadian Council on Animal Care, OttawaGoogle Scholar
- 51.Chomczynsky P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159Google Scholar
- 64.Zhang X, Heng X, Li T, Li L, Yang D, Zhang X, Du Y, Doody RS, Le W (2011) Long-term treatment with lithium alleviates memory deficits and reduces amyloid-β production in an aged Alzheimer’s disease transgenic mouse model. J Alzheimer’s Dis 24:739–749Google Scholar
- 67.Aprahamian I, Santos FS, Dos Santos B, Talib L, Diniz BS, Radanovic M, Gattaz WF, Forlenza OV (2014) Long-term, low-dose lithium treatment does not impair renal function in the elderly: a 2-year randomized, placebo-controlled trial followed by single-blind extension. J Clin Psychiatry 75:e672–e678CrossRefPubMedGoogle Scholar
- 78.Schaeffer EL, Bassi F Jr, Gattaz WF (2005) Inhibition of phospholipase A2 activity reduces membrane fluidity in rat hippocampus. J Neurotransm 112:641–647Google Scholar
- 85.Vakhapova V, Cohen T, Richter Y, Herzog Y, Kam Y, Korczyn AD (2014) Phosphatidylserine containing omega-3 Fatty acids may improve memory abilities in nondemented elderly individuals with memory complaints: results from an open-label extension study. Dement Geriatr Cogn Disord 38:39–45CrossRefPubMedGoogle Scholar