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Prenatal Hypoxia Induces Premature Aging Accompanied by Impaired Function of the Glutamatergic System in Rat Hippocampus.
- Source :
-
Neurochemical research [Neurochem Res] 2021 Mar; Vol. 46 (3), pp. 550-563. Date of Electronic Publication: 2021 Jan 02. - Publication Year :
- 2021
-
Abstract
- Prenatal hypoxia is among leading causes of progressive brain pathologies in postnatal life. This study aimed to analyze the characteristics of the hippocampal glutamatergic system and behavior of rats in early (2 weeks), adult (3 months) and advanced (18 months) postnatal ontogenesis after exposure to prenatal severe hypoxia (PSH, 180 Torr, 5% O2, 3 h) during the critical period in the formation of the hippocampus (days 14-16 of gestation). We have shown an age-dependent progressive decrease in the hippocampal glutamate levels, a decrease of the neuronal cell number in the CA1 hippocampal region, as well as impairment of spatial long-term memory in the Morris water navigation task. The gradual decrease of glutamate was accompanied by decreased expression of the genes that mediate glutamate metabolism and recycling in the hippocampus. That deficiency apparently correlated with an increase of the metabotropic glutamate receptor type 1 (mGluR1) and synaptophysin expression. Generation of the lipid peroxidation products in the hippocampus of adult rats subjected to prenatal severe hypoxia (PSH rats) was not increased compared to the control animals when tested in a model of glutamate excitotoxicity induced by severe hypoxia. This demonstrates that excessive glutamate sensitivity in PSH rats does not compensate for glutamate deficiency. Our results show a significant contribution of the glutamate system dysfunction to age-associated decrease of this mediator, cognitive decline, and early neuronal loss in PSH rats.
- Subjects :
- Aging, Premature etiology
Aging, Premature pathology
Amino Acid Transport System A metabolism
Animals
Animals, Newborn
CA1 Region, Hippocampal pathology
Female
Hypoxia complications
Hypoxia pathology
Male
Morris Water Maze Test physiology
Pregnancy
Rats
Receptors, AMPA metabolism
Vesicular Glutamate Transport Protein 1 metabolism
Aging, Premature physiopathology
CA1 Region, Hippocampal metabolism
Glutamic Acid metabolism
Hypoxia physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 1573-6903
- Volume :
- 46
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Neurochemical research
- Publication Type :
- Academic Journal
- Accession number :
- 33389385
- Full Text :
- https://doi.org/10.1007/s11064-020-03191-z