THE MOLECULAR MECHANISMS AFFECTING N-ACETYLASPARTATE HOMEOSTASIS FOLLOWING EXPERIMENTAL GRADED TRAUMATIC BRAIN INJURY.

Barbara Tavazzi, Valentina Di Pietro, Angela Maria Amorini, Giacomo Lazzarino, Giuseppe Lazzarino, Roberto Vagnozzi, Ann Logan, Stefano Signoretti, Antonio Belli

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22 Citazioni (Scopus)

Abstract

To characterize the molecular mechanisms of N-acetylaspartate (NAA) metabolism following traumatic brain injury (TBI), we measured the NAA, ATP and ADP concentrations and calculated the ATP/ADP ratio at different times from impact, concomitantly evaluating the gene and protein expressions controlling NAA homeostasis (the NAA synthesizing and degrading enzymes N-acetyltransferase 8-like and aspartoacylase, respectively) in rats receiving either mild or severe TBI. The reversible changes in NAA induced by mild TBI were due to a combination of transient mitochondrial malfunctioning with energy crisis (decrease in ATP and in the ATP/ADP ratio) and modulation in the gene and protein levels of N-acetyltransferase 8-like and increase of aspartoacylase levels. The irreversible decrease in NAA following severe TBI, was instead characterized by profound mitochondrial malfunctioning (constant 65% decrease of the ATP/ADP indicating permanent impairment of the mitochondrial phosphorylating capacity), dramatic repression of the N-acetyltransferase 8-like gene and concomitant remarkable increase in the aspartoacylase gene and protein levels. The mechanisms underlying changes in NAA homeostasis following graded TBI might be of note for possible new therapeutic approaches and will help in understanding the effects of a repeat concussion occurring during particular periods of the complex NAA recovery process, coincident with the so called window of brain vulnerability.
Lingua originaleEnglish
pagine (da-a)1 4 7-1 5 7
Numero di pagine10
RivistaJournal of Molecular Medicine
Volume2014
DOI
Stato di pubblicazionePubblicato - 2014

Keywords

  • Homeostasis
  • N-acetylaspartate
  • gravity
  • traumatic brain injury

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