Home > Research > Publications & Outputs > Inflammatory, synaptic, motor, and behavioral a...

Links

Text available via DOI:

View graph of relations

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

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Published

Standard

Inflammatory, synaptic, motor, and behavioral alterations induced by gestational sepsis on the offspring at different stages of life. / Granja, Marcelo Gomes; Alves, Letícia Pires; Leardini-Tristão, Marina et al.
In: Journal of neuroinflammation, Vol. 18, No. 1, 60, 25.02.2021.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Harvard

Granja, MG, Alves, LP, Leardini-Tristão, M, Saul, ME, Bortoni, LC, de Moraes, FM, Ferreira, EC, de Moraes, BPT, da Silva, VZ, Dos Santos, AFR, Silva, AR, Gonçalves-de-Albuquerque, CF, Bambini-Junior, V, Weyrich, AS, Rondina, MT, Zimmerman, GA & de Castro-Faria-Neto, HC 2021, 'Inflammatory, synaptic, motor, and behavioral alterations induced by gestational sepsis on the offspring at different stages of life', Journal of neuroinflammation, vol. 18, no. 1, 60. https://doi.org/10.1186/s12974-021-02106-1

APA

Granja, M. G., Alves, L. P., Leardini-Tristão, M., Saul, M. E., Bortoni, L. C., de Moraes, F. M., Ferreira, E. C., de Moraes, B. P. T., da Silva, V. Z., Dos Santos, A. F. R., Silva, A. R., Gonçalves-de-Albuquerque, C. F., Bambini-Junior, V., Weyrich, A. S., Rondina, M. T., Zimmerman, G. A., & de Castro-Faria-Neto, H. C. (2021). Inflammatory, synaptic, motor, and behavioral alterations induced by gestational sepsis on the offspring at different stages of life. Journal of neuroinflammation, 18(1), Article 60. https://doi.org/10.1186/s12974-021-02106-1

Vancouver

Granja MG, Alves LP, Leardini-Tristão M, Saul ME, Bortoni LC, de Moraes FM et al. Inflammatory, synaptic, motor, and behavioral alterations induced by gestational sepsis on the offspring at different stages of life. Journal of neuroinflammation. 2021 Feb 25;18(1):60. doi: 10.1186/s12974-021-02106-1

Author

Granja, Marcelo Gomes ; Alves, Letícia Pires ; Leardini-Tristão, Marina et al. / Inflammatory, synaptic, motor, and behavioral alterations induced by gestational sepsis on the offspring at different stages of life. In: Journal of neuroinflammation. 2021 ; Vol. 18, No. 1.

Bibtex

@article{2e1db775394548e39981c3a28089364f,
title = "Inflammatory, synaptic, motor, and behavioral alterations induced by gestational sepsis on the offspring at different stages of life",
abstract = "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 14th embryonic day (E14) were intratracheally instilled with saline 0.9% solution (control group) or Klebsiella spp. (3 × 108 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.",
keywords = "Animals, Behavior, Animal, Brain/immunology, Cognitive Dysfunction/etiology, Female, Inflammation, Mice, Motor Activity/physiology, Pregnancy, Prenatal Exposure Delayed Effects/immunology, Sepsis/complications, Synapses/metabolism",
author = "Granja, {Marcelo Gomes} and Alves, {Let{\'i}cia Pires} and Marina Leardini-Trist{\~a}o and Saul, {Michelle Edelman} and Bortoni, {Let{\'i}cia Coelho} and {de Moraes}, {Fl{\'a}via Maciel} and Ferreira, {Erica Camila} and {de Moraes}, {Bianca Portugal Tavares} and {da Silva}, {Vict{\'o}ria Zerboni} and {Dos Santos}, {Adrielle Ferreira Ribeiro} and Silva, {Adriana Ribeiro} and Gon{\c c}alves-de-Albuquerque, {Cassiano Felippe} and Victorio Bambini-Junior and Weyrich, {Andrew S} and Rondina, {Matthew T} and Zimmerman, {Guy A} and {de Castro-Faria-Neto}, {Hugo Caire}",
year = "2021",
month = feb,
day = "25",
doi = "10.1186/s12974-021-02106-1",
language = "English",
volume = "18",
journal = "Journal of neuroinflammation",
issn = "1742-2094",
publisher = "BioMed Central Ltd.",
number = "1",

}

RIS

TY - JOUR

T1 - Inflammatory, synaptic, motor, and behavioral alterations induced by gestational sepsis on the offspring at different stages of life

AU - Granja, Marcelo Gomes

AU - Alves, Letícia Pires

AU - Leardini-Tristão, Marina

AU - Saul, Michelle Edelman

AU - Bortoni, Letícia Coelho

AU - de Moraes, Flávia Maciel

AU - Ferreira, Erica Camila

AU - de Moraes, Bianca Portugal Tavares

AU - da Silva, Victória Zerboni

AU - Dos Santos, Adrielle Ferreira Ribeiro

AU - Silva, Adriana Ribeiro

AU - Gonçalves-de-Albuquerque, Cassiano Felippe

AU - Bambini-Junior, Victorio

AU - Weyrich, Andrew S

AU - Rondina, Matthew T

AU - Zimmerman, Guy A

AU - de Castro-Faria-Neto, Hugo Caire

PY - 2021/2/25

Y1 - 2021/2/25

N2 - 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 14th embryonic day (E14) were intratracheally instilled with saline 0.9% solution (control group) or Klebsiella spp. (3 × 108 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.

AB - 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 14th embryonic day (E14) were intratracheally instilled with saline 0.9% solution (control group) or Klebsiella spp. (3 × 108 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.

KW - Animals

KW - Behavior, Animal

KW - Brain/immunology

KW - Cognitive Dysfunction/etiology

KW - Female

KW - Inflammation

KW - Mice

KW - Motor Activity/physiology

KW - Pregnancy

KW - Prenatal Exposure Delayed Effects/immunology

KW - Sepsis/complications

KW - Synapses/metabolism

U2 - 10.1186/s12974-021-02106-1

DO - 10.1186/s12974-021-02106-1

M3 - Journal article

C2 - 33632243

VL - 18

JO - Journal of neuroinflammation

JF - Journal of neuroinflammation

SN - 1742-2094

IS - 1

M1 - 60

ER -