Maternal antioxidant treatment protects adult offspring against memory loss and hippocampal atrophy in a rodent model of developmental hypoxia.
Animals
Animals, Newborn
Antioxidants
/ therapeutic use
Ascorbic Acid
/ therapeutic use
Atrophy
/ drug therapy
Dietary Supplements
Disease Models, Animal
Female
Fetal Growth Retardation
/ drug therapy
Fetal Hypoxia
/ complications
Hippocampus
/ drug effects
Male
Memory Disorders
/ drug therapy
Pregnancy
Pregnancy Complications
/ drug therapy
Prenatal Exposure Delayed Effects
/ drug therapy
Rats
Rats, Wistar
brain
fetal hypoxia
hippocampus
memory
programming
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
revised:
11
02
2021
received:
23
11
2020
accepted:
11
02
2021
entrez:
23
4
2021
pubmed:
24
4
2021
medline:
21
7
2021
Statut:
ppublish
Résumé
Chronic fetal hypoxia is one of the most common outcomes in complicated pregnancy in humans. Despite this, its effects on the long-term health of the brain in offspring are largely unknown. Here, we investigated in rats whether hypoxic pregnancy affects brain structure and function in the adult offspring and explored underlying mechanisms with maternal antioxidant intervention. Pregnant rats were randomly chosen for normoxic or hypoxic (13% oxygen) pregnancy with or without maternal supplementation with vitamin C in their drinking water. In one cohort, the placenta and fetal tissues were collected at the end of gestation. In another, dams were allowed to deliver naturally, and offspring were reared under normoxic conditions until 4 months of age (young adult). Between 3.5 and 4 months, the behavior, cognition and brains of the adult offspring were studied. We demonstrated that prenatal hypoxia reduced neuronal number, as well as vascular and synaptic density, in the hippocampus, significantly impairing memory function in the adult offspring. These adverse effects of prenatal hypoxia were independent of the hypoxic pregnancy inducing fetal growth restriction or elevations in maternal or fetal plasma glucocorticoid levels. Maternal vitamin C supplementation during hypoxic pregnancy protected against oxidative stress in the placenta and prevented the adverse effects of prenatal hypoxia on hippocampal atrophy and memory loss in the adult offspring. Therefore, these data provide a link between prenatal hypoxia, placental oxidative stress, and offspring brain health in later life, providing insight into mechanism and identifying a therapeutic strategy.
Identifiants
pubmed: 33891326
doi: 10.1096/fj.202002557RR
doi:
Substances chimiques
Antioxidants
0
Ascorbic Acid
PQ6CK8PD0R
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e21477Subventions
Organisme : RCUK | Medical Research Council (MRC)
ID : MC_UU_00014/4
Organisme : British Heart Foundation
ID : RG/17/8/32924
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/12/74/29778
Pays : United Kingdom
Organisme : British Heart Foundation
ID : PG/14/5/30547
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/06/006/22028
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00014/4
Pays : United Kingdom
Informations de copyright
© 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
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