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Lithium-induced neuroprotective activity in neuronal and microglial cells: A purinergic perspective.
Gubert, Carolina; Andrejew, Roberta; Figueiro, Fabricio; Bergamin, Letícia; Kapczinski, Flávio; Magalhães, Pedro Vieira da Silva; Battastini, Ana Maria Oliveira.
Afiliación
  • Gubert C; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil. Electronic address: gubert.cm@gmail.com.
  • Andrejew R; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil.
  • Figueiro F; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil.
  • Bergamin L; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil.
  • Kapczinski F; Department of Psychiatry and Behavioral Sciences, MacMaster University, Hamilton, Canada.
  • Magalhães PVDS; Universidade Federal do Rio Grande do Sul, Hospital de Clínicas de Porto Alegre, Centro de Pesquisa Experimental, Graduate Program in Psychiatry and Behavioral Sciences, Brazil.
  • Battastini AMO; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil.
Psychiatry Res ; 295: 113562, 2021 01.
Article en En | MEDLINE | ID: mdl-33213934
Lithium is the mainstay of pharmacotherapy for treating bipolar disorder (BD). However, despite its wide use for over 60 years in the clinic, its mechanisms of action are not yet well defined. Elucidating lithium's mechanism of action will not only shed light on the pathophysiology of BD, but also potentially uncover new treatment targets. Previous studies suggest that the purinergic system may be involved in lithium's neuroprotective action; thus, the specific aim of this study is to better understand the neuroprotective action of lithium against ATP-induced cellular effect in both neuronal and microglial cellular lineages. We used PC12 neuronal and N9 microglial cells, evaluating cell death by cell counting and Annexin/PI cytometry assay, P2 × 7R immunocontent and ectonucleotidases activity, together with cytokine and nitrite assessment for microglial activity determination. Our results indicate that cells of different neural origins are responsive to ATP, in the sense of neuronal excitotoxicity and microglial switch into an activated M1-like phenotype respectively. Lithium, in turn, modulates the response in neuronal PC12 cells, preventing ATP-induced cell death. On the other hand, in N9 microglial cells, lithium was unable to prevent ATP-induced activation via P2 × 7R, indicating that lithium protective action against the effects of ATP more likely occurs in neurons rather than in microglia. Further studies are needed to better characterize the involvement of the purinergic system in the mechanism of action of lithium against neuronal death and microglial activation, in order to uncover new therapeutic adjunctive targets, such as antagonism of P2 × 7R, as potential approach for bipolar disorder treatment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastorno Bipolar / Neuroprotección / Litio Límite: Animals / Humans Idioma: En Revista: Psychiatry Res Año: 2021 Tipo del documento: Article Pais de publicación: Irlanda
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastorno Bipolar / Neuroprotección / Litio Límite: Animals / Humans Idioma: En Revista: Psychiatry Res Año: 2021 Tipo del documento: Article Pais de publicación: Irlanda