Fructose-1,6-Bisphosphate Protects Hippocampal Rat Slices from NMDA Excitotoxicity

Barbara Tavazzi, Giacomo Lazzarino, Kamal M. Yakoub, Angela M. Amorini, Giuseppe Caruso, Concetta Scazzone, Marcello Ciaccio, Giuseppe Lazzarino, Antonio Belli, Valentina Di Pietro

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1 Citazioni (Scopus)

Abstract

Effects of fructose 1,6-bisphosphate (F-1,6-P2) towards N-methyl-d-aspartate NMDA excitotoxicity were evaluated in rat organotypic hippocampal brain slice cultures (OHSC) challenged for 3 h with 30 μM NMDA, followed by incubations (24, 48, and 72 h) without (controls) and with F-1,6-P2 (0.5, 1 or 1.5 mM). At each time, cell necrosis was determined by measuring LDH in the medium. Energy metabolism was evaluated by measuring ATP, GTP, ADP, AMP, and ATP catabolites (nucleosides and oxypurines) in deproteinized OHSC extracts. Gene expressions of phosphofructokinase, aldolase, and glyceraldehyde-3-phosphate dehydrogenase were also measured. F-1,6-P2 dose-dependently decreased NMDA excitotoxicity, abolishing cell necrosis at the highest concentration tested (1.5 mM). Additionally, F-1,6-P2 attenuated cell energy imbalance caused by NMDA, ameliorating the mitochondrial phosphorylating capacity (increase in ATP/ADP ratio) Metabolism normalization occurred when using 1.5 mM F-1,6-P2. Remarkable increase in expressions of phosphofructokinase, aldolase and glyceraldehyde-3-phosphate dehydrogenase (up to 25 times over the values of controls) was also observed. Since this phenomenon was recorded even in OHSC treated with F-1,6-P2 with no prior challenge with NMDA, it is highly conceivable that F-1,6-P2 can enter into intact cerebral cells producing significant benefits on energy metabolism. These effects are possibly mediated by changes occurring at the gene level, thus opening new perspectives for F-1,6-P2 application as a useful adjuvant to rescue mitochondrial metabolism of cerebral cells under stressing conditions.
Lingua originaleEnglish
pagine (da-a)2239-2245
Numero di pagine7
RivistaInternational Journal of Molecular Sciences
Volume2020
DOI
Stato di pubblicazionePubblicato - 2019

Keywords

  • 6-bisphosphate
  • N-methyl-d-aspartate
  • energymetabolism
  • excitotoxicity
  • fructose-1
  • mitochondrial dysfunction
  • organotypic hippocampal brainslice cultures

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