Glycolytic and Krebs cycle enzymes activity in rat prefrontal cortex, hippocampus, and striatum after single and repeated NMDA inhibition by MK-801
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
35219782
DOI
10.1016/j.neuro.2022.02.005
PII: S0161-813X(22)00024-9
Knihovny.cz E-resources
- Keywords
- Citrate synthase, Energy metabolism, Hexokinase, Lactate dehydrogenase, Malate dehydrogenase, Schizophrenia,
- MeSH
- Citric Acid Cycle MeSH
- Citrate (si)-Synthase metabolism pharmacology MeSH
- Dizocilpine Maleate * pharmacology MeSH
- Hexokinase metabolism pharmacology MeSH
- Hippocampus MeSH
- Rats MeSH
- L-Lactate Dehydrogenase metabolism MeSH
- Humans MeSH
- N-Methylaspartate * pharmacology MeSH
- Rats, Wistar MeSH
- Prefrontal Cortex MeSH
- Receptors, N-Methyl-D-Aspartate metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Citrate (si)-Synthase MeSH
- Dizocilpine Maleate * MeSH
- Hexokinase MeSH
- L-Lactate Dehydrogenase MeSH
- N-Methylaspartate * MeSH
- Receptors, N-Methyl-D-Aspartate MeSH
Psychosis is a state of altered thoughts which often accompanies schizophrenia. It was suggested that changes in energetic metabolism accompany psychosis and post-psychosis states. Here, we use the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 to experimentally induce psychosis-like behavior in rats. We addressed an effect of single and repeated (5×) MK-801 application (0.3 mg/kg; i.p.) on the energy metabolism in homogenates and crude mitochondrial fraction (CMF) of the striatum (STR), prefrontal cortex (PFC), and the hippocampus (HIP) of the adult male Wistar rat (n = 39). In each brain region, we assessed activity of glycolytic (hexokinase (HK) and lactate dehydrogenase (LDH)) and Krebs cycle enzymes (citrate synthase (CS) and malate dehydrogenase (MDH)) 2 h and 3 days (3d) after the last MK-801 application together with relative respiratory rates assessment in tissue homogenate. In STR, a single MK-801 application led to a decrease in the LDH (p = 0.0035) and the increase of the MDH (p = 0.0043) activities following 3d. Therein, repeated MK-801 doses evoked increased LDH (p = 0.0204) and CS (p = 0.0019) activities in the homogenate 2 h and increased HK (p = 0.0007) 3d after the last application. Elevated HK activity within CMF was observed after 3d (p = 0.0054). In PFC, repeated MK-801 application decreased HK activity in the homogenate 3d after the final application (p = 0.0234). Correspondingly, PFC HK activity in CMF of repeated administration samples dropped (p = 0.003). In HIP, repeated MK-801 administration led to increased respiration of SDH (p = 0.0475) only 2 h after the last application and decreased CS activity (p = 0.0160) was observed 3d after the last application. Our results indicate a progressive metabolic dysregulation of glycolytic and Krebs cycle enzymes following repeated inhibition of NMDA receptors activity in a region-specific manner. Energetic alterations may form a basis for persisting cognitive problems during and following a psychosis in schizophrenia patients.
Faculty of Science Charles University Prague Czech Republic
Institute of Physiology Czech Academy of Sciences Prague Czech Republic
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