Glycolytic and Krebs cycle enzymes activity in rat prefrontal cortex, hippocampus, and striatum after single and repeated NMDA inhibition by MK-801

0557063 - FGÚ 2023 RIV NL eng J - Článek v odborném periodiku
Kolář, D. - Kletečková, L. - Skálová, K. - Brožka, Hana - Kalous, M. - Valeš, Karel
Glycolytic and Krebs cycle enzymes activity in rat prefrontal cortex, hippocampus, and striatum after single and repeated NMDA inhibition by MK-801.
Neurotoxicology. Roč. 90, May (2022), s. 35-47. ISSN 0161-813X. E-ISSN 1872-9711
Grant CEP: GA ČR(CZ) GA18-09296S; GA MZd(CZ) EF16_025/0007444; GA MZd(CZ) NU20-04-00389; GA ČR(CZ) GA22-15096S
Institucionální podpora: RVO:67985823
Klíčová slova: energy metabolism * hexokinase * lactate dehydrogenase * citrate synthase * malate dehydrogenase * schizophrenia
Obor OECD: Pharmacology and pharmacy
Impakt faktor: 3.4, rok: 2022
Způsob publikování: Omezený přístup
https://doi.org/10.1016/j.neuro.2022.02.005

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 (5x) 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.
Trvalý link: http://hdl.handle.net/11104/0331183