Phytoestrogen coumestrol attenuates brain mitochondrial dysfunction and long-term cognitive deficits following neonatal hypoxia-ischemia.


Journal

International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience
ISSN: 1873-474X
Titre abrégé: Int J Dev Neurosci
Pays: United States
ID NLM: 8401784

Informations de publication

Date de publication:
Dec 2019
Historique:
received: 01 07 2019
revised: 21 10 2019
accepted: 21 10 2019
pubmed: 7 11 2019
medline: 12 5 2020
entrez: 7 11 2019
Statut: ppublish

Résumé

Neonatal Hypoxia-Ischemia (HI) is a major cause of morbidity and mortality, and is frequently associated with short and long-term neurologic and cognitive impairments. The HI injury causes mitochondrial damage leading to increased production of reactive oxygen species (ROS). Phytoestrogens are non-steroidal plant substances structurally and functionally similar to estrogen. Coumestrol is a potent isoflavonoid with a protective effect against ischemic brain damage in adult rats. Our aim was to determine if coumestrol treatment following neonatal HI attenuates the long-term cognitive deficits induced by neonatal HI, as well as to investigate one possible mechanism underlying its potential effect. On the 7th postnatal day, male Wistar rats were submitted to the Levine-Rice HI model. Intraperitoneal injections of 20 mg/kg of coumestrol, or vehicle, were administered immediately pre-hypoxia or 3 h post-hypoxia. At 12 h after HI the mitochondrial status and ROS levels were determined. At 60th postnatal day the cognitive deficits were revealed in the Morris water maze reference and working spatial memories. Following behavioral analysis, histological assessment was performed and reactive astrogliosis was measured by GFAP expression. Results demonstrate that both pre- and post-HI administration of coumestrol were able to counteract the long-term cognitive and morphological impairments caused by HI, as well as to block the late reactive astrogliosis. The pre-HI administration of coumestrol was able to prevent the early mitochondrial dysfunction in the hippocampus of injured rat pups. Present data suggest that coumestrol exerts protection against experimental neonatal brain hypoxia-ischemia through, at least in part, early modulation of mitochondrial function.

Identifiants

pubmed: 31693927
doi: 10.1016/j.ijdevneu.2019.10.009
doi:

Substances chimiques

Neuroprotective Agents 0
Phytoestrogens 0
Reactive Oxygen Species 0
Coumestrol V7NW98OB34

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

86-95

Informations de copyright

Copyright © 2019 ISDN. Published by Elsevier Ltd. All rights reserved.

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Auteurs

Janine Beatriz Ramos Anastacio (JBR)

Post-graduation Program in Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.

Eduardo Farias Sanches (EF)

Department of Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.

Fabrício Nicola (F)

Post-graduation Program in Neuroscience, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.

Felipe Odorcyk (F)

Post-graduation Program in Phisiology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.

Rafael Bandeira Fabres (RB)

Post-graduation Program in Phisiology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.

Carlos Alexandre Netto (CA)

Post-graduation Program in Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
Department of Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
Post-graduation Program in Neuroscience, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
Post-graduation Program in Phisiology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.

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