title: Lithium activates brain phospholipase A2 and improves memory in rats: implications for Alzheimer's disease.
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.
authors.affiliation: 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.|Pós-Graduação Interunidades em Biotecnologia, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Fábio B
authors.initials: FB
authors.lastname: Mury
authors.affiliation: Centro de Memória, Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil.|Departamento de Farmácia, Universidade Estadual do Centro-Oeste, Guarapuava, PR, Brazil.
authors.forename: Weber C
authors.initials: WC
authors.lastname: da Silva
authors.affiliation: 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.
authors.forename: Nádia R
authors.initials: NR
authors.lastname: Barbosa
authors.affiliation: 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.|Pós-Graduação Interunidades em Biotecnologia, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Camila T
authors.initials: CT
authors.lastname: Mendes
authors.affiliation: Centro de Memória, Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil.|Departamento de Farmácia, Universidade Estadual do Centro-Oeste, Guarapuava, PR, Brazil.
authors.forename: Juliana S
authors.initials: JS
authors.lastname: Bonini
authors.affiliation: Instituto de Pesquisas Energéticas e Nucleares-IPEN-CNEN/SP, Grupo de Caracterização Química e Isotópica, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Jorge Eduardo Souza
authors.initials: JE
authors.lastname: Sarkis
authors.affiliation: Laboratório de Pesquisa de Memória, Instituto do Cérebro, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.
authors.forename: Martin
authors.initials: M
authors.lastname: Cammarota
authors.affiliation: Centro de Memória, Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Ivan
authors.initials: I
authors.lastname: Izquierdo
authors.affiliation: 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. gattaz@usp.br.
authors.forename: Wagner F
authors.initials: WF
authors.lastname: Gattaz
authors.affiliation: 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. Emmanueldias@gmail.com.|Laboratório de Genômica Médica, Centro Internacional de Pesquisas, AC Camargo Cancer Center, São Paulo, SP, Brazil. Emmanueldias@gmail.com.
authors.forename: Emmanuel
authors.identifier: http://orcid.org/0000-0001-5670-8559
authors.initials: E
authors.lastname: Dias-Neto
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology*; D018020:Lithium Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D057567:Memory, Long-Term / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D054467:Phospholipases A2 / Q000187:drug effects* / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018020:Lithium Compounds; D018696:Neuroprotective Agents; D054467:Phospholipases A2
keywords: Gene expression; Hippocampus; Lithium; Memory; PLA2; Step-down inhibitory avoidance task