Inflammatory, synaptic, motor, and behavioral alterations induced by gestational sepsis on the offspring at different stages of life.

Autor: Granja MG; Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz - Fiocruz, Rio de Janeiro, Brazil.; Programa de Pós-graduação em Biologia Molecular e Celular, Universidade Federal do Estado do Rio de Janeiro - UNIRIO, Rio de Janeiro, Brazil., Alves LP; Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz - Fiocruz, Rio de Janeiro, Brazil.; Programa de Pós-graduação em Biologia Molecular e Celular, Universidade Federal do Estado do Rio de Janeiro - UNIRIO, Rio de Janeiro, Brazil., Leardini-Tristão M; Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz - Fiocruz, Rio de Janeiro, Brazil., Saul ME; Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz - Fiocruz, Rio de Janeiro, Brazil.; Faculdade de Medicina, Universidade Estácio de Sá - UNESA, Rio de Janeiro, Brazil., Bortoni LC; Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz - Fiocruz, Rio de Janeiro, Brazil.; Faculdade de Medicina, Universidade Estácio de Sá - UNESA, Rio de Janeiro, Brazil., de Moraes FM; Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz - Fiocruz, Rio de Janeiro, Brazil., Ferreira EC; Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz - Fiocruz, Rio de Janeiro, Brazil., de Moraes BPT; Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz - Fiocruz, Rio de Janeiro, Brazil.; Programa de Pós-graduação em Neurociências, Universidade Federal Fluminense - UFF, Niterói, Rio de Janeiro, Brazil., da Silva VZ; Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz - Fiocruz, Rio de Janeiro, Brazil., Dos Santos AFR; Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz - Fiocruz, Rio de Janeiro, Brazil., Silva AR; Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz - Fiocruz, Rio de Janeiro, Brazil., Gonçalves-de-Albuquerque CF; Programa de Pós-graduação em Biologia Molecular e Celular, Universidade Federal do Estado do Rio de Janeiro - UNIRIO, Rio de Janeiro, Brazil., Bambini-Junior V; School of Pharmacy and Biomedical Sciences, University of Central Lancashire, PR1 2HE, Lancashire, Preston, England, UK., Weyrich AS; School of Pharmacy and Biomedical Sciences, University of Central Lancashire, PR1 2HE, Lancashire, Preston, England, UK., Rondina MT; Department of Internal Medicine and Molecular Medicine Program, University of Utah, Salt Lake City, UT, USA.; Department of Internal Medicine and Pathology, University of Utah, Salt Lake City, UT, USA.; Department of Internal Medicine and GRECC, George E. Wahlen VAMC, Salt Lake City, UT, USA., Zimmerman GA; Department of Internal Medicine and Molecular Medicine Program, University of Utah, Salt Lake City, UT, USA., de Castro-Faria-Neto HC; Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz - Fiocruz, Rio de Janeiro, Brazil. hugocfneto@gmail.com.
Jazyk: angličtina
Zdroj: Journal of neuroinflammation [J Neuroinflammation] 2021 Feb 25; Vol. 18 (1), pp. 60. Date of Electronic Publication: 2021 Feb 25.
DOI: 10.1186/s12974-021-02106-1
Abstrakt: Background: The term sepsis is used to designate a systemic condition of infection and inflammation associated with hemodynamic changes that result in organic dysfunction. Gestational sepsis can impair the development of the central nervous system and may promote permanent behavior alterations in the offspring. The aim of our work was to evaluate the effects of maternal sepsis on inflammatory cytokine levels and synaptic proteins in the hippocampus, neocortex, frontal cortex, and cerebellum of neonatal, young, and adult mice. Additionally, we analyzed the motor development, behavioral features, and cognitive impairments in neonatal, young and adult offspring.
Methods: Pregnant mice at the 14 th embryonic day (E14) were intratracheally instilled with saline 0.9% solution (control group) or Klebsiella spp. (3 × 10 8 CFU) (sepsis group) and started on meropenem after 5 h. The offspring was sacrificed at postnatal day (P) 2, P8, P30, and P60 and samples of liver, lung, and brain were collected for TNF-α, IL-1β, and IL-6 measurements by ELISA. Synaptophysin, PSD95, and β-tubulin levels were analyzed by Western blot. Motor tests were performed at all analyzed ages and behavioral assessments were performed in offspring at P30 and P60.
Results: Gestational sepsis induces a systemic pro-inflammatory response in neonates at P2 and P8 characterized by an increase in cytokine levels. Maternal sepsis induced systemic downregulation of pro-inflammatory cytokines, while in the hippocampus, neocortex, frontal cortex, and cerebellum an inflammatory response was detected. These changes in the brain immunity were accompanied by a reduction of synaptophysin and PSD95 levels in the hippocampus, neocortex, frontal cortex, and cerebellum, in all ages. Behavioral tests demonstrated motor impairment in neonates, and depressive-like behavior, fear-conditioned memory, and learning impairments in animals at P30 and P60, while spatial memory abilities were affected only at P60, indicating that gestational sepsis not only induces an inflammatory response in neonatal mouse brains, but also affects neurodevelopment, and leads to a plethora of behavioral alterations and cognitive impairments in the offspring.
Conclusion: These data suggest that maternal sepsis may be causatively related to the development of depression, learning, and memory impairments in the litter.
Databáze: MEDLINE
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