Hippocampal Sector-Specific Metabolic Profiles Reflect Endogenous Strategy for Ischemia-Reperfusion Insult Resistance.
CA1
Gyrus dentatus
Hippocampus
Ischemia-reperfusion injury
LC-QTOF-MS
Meriones unguiculatus
Transient ischemic episode
Untargeted metabolomics
Journal
Molecular neurobiology
ISSN: 1559-1182
Titre abrégé: Mol Neurobiol
Pays: United States
ID NLM: 8900963
Informations de publication
Date de publication:
Apr 2021
Apr 2021
Historique:
received:
09
07
2020
accepted:
12
11
2020
pubmed:
23
11
2020
medline:
28
10
2021
entrez:
22
11
2020
Statut:
ppublish
Résumé
The gerbil is a well-known model for studying cerebral ischemia. The CA1 of the hippocampus is vulnerable to 5 min of ischemia, while the CA2-4 and dentate gyrus (DG) are resistant to it. Short-lasting ischemia, a model of transient ischemic attacks in men, results in CA1 neuron death within 2-4 days of reperfusion. Untargeted metabolomics, using LC-QTOF-MS, was used to enrich the knowledge about intrinsic vulnerability and resistance of hippocampal regions and their early post-ischemic response (IR). In total, 30 significant metabolites were detected. In controls, taurine was significantly lower and guanosine monophosphate was higher in CA1, as compared to that in CA2-4,DG. LysoPG and LysoPE were more abundant in CA1, while LysoPI 18:0 was detected only in CA2-4,DG. After IR, a substantial decrease in the citric acid level in CA1, an accumulation of pipecolic acid in both regions, and opposite changes in the amount of PE and LysoPE were observed. The following metabolic pathways were identified as being differentially active in control CA1 vs. CA2-4,DG: metabolism of taurine and hypotaurine, glycerophospholipid, and purine. These results may indicate that a regulation of cell volume, altered structure of cell membranes, and energy metabolism differentiate hippocampal regions. Early post-ischemia, spatial differences in the metabolism of aminoacyl-tRNA biosynthesis, and amino acids and their metabolites with a predominance of those which upkeep their well-being in CA2-4,DG are shown. Presented results are consistent with genetic, morphological, and functional data, which may be useful in further study on endogenous mechanisms of neuroprotection and search for new targets for therapeutic interventions.
Identifiants
pubmed: 33222147
doi: 10.1007/s12035-020-02208-6
pii: 10.1007/s12035-020-02208-6
pmc: PMC7932963
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1621-1633Références
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