Minocycline inhibits microglial activation in the CA1 hippocampal region and prevents long-term cognitive sequel after experimental cerebral malaria.

Autor: Moreira ET; Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil; Universidade Cruzeiro do Sul, Brazil; Departamento de Bioquímica, Instituto de Biologia Roberto Alcântara Gomes, Universidade Estadual do Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: emilio.telles.02@gmail.com., Lourenço MP; Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil., Cunha-Fernandes T; Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil., Silva TI; Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil., Siqueira LD; Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil., Castro-Faria-Neto HC; Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil., Reis PA; Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil; Departamento de Bioquímica, Instituto de Biologia Roberto Alcântara Gomes, Universidade Estadual do Rio de Janeiro, Rio de Janeiro, Brazil.
Jazyk: angličtina
Zdroj: Journal of neuroimmunology [J Neuroimmunol] 2024 Dec 15; Vol. 397, pp. 578480. Date of Electronic Publication: 2024 Oct 29.
DOI: 10.1016/j.jneuroim.2024.578480
Abstrakt: Cerebral malaria is the worst complication of malaria infection, has a high mortality rate, and may cause different neurodysfunctions, including cognitive decline. Neuroinflammation is an important cause of cognitive damage in neurodegenerative diseases, and microglial cells can be activated in a disease-associated profile leading to tissue damage and neuronal death. Here, we demonstrated that treatment with minocycline reduced blood-brain barrier breakdown and modulated ICAM1 mRNA expression; reduced proinflammatory cytokines, such as TNF-α, IL-1β, IFN-γ, and IL-6; and prevented long-term cognitive decline in contextual and aversive memory tasks. Taken together, our data suggest that microglial cells are activated during experimental cerebral malaria, leading to neuroinflammatory events that end up in cognitive damage. In addition, pharmacological modulation of microglial activation, by drugs such as minocycline may be an important therapeutic strategy in the prevention of long-term memory impairment.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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