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Molecular Medicine

, Volume 20, Issue 1, pp 147–157 | Cite as

The Molecular Mechanisms Affecting N-Acetylaspartate Homeostasis Following Experimental Graded Traumatic Brain Injury

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

Abstract

To characterize the molecular mechanisms of N-acetylaspartate (NAA) metabolism following traumatic brain injury (TBI), we measured the NAA, adenosine triphosphate (ATP) and adenosine diphosphate (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 repeat concussions occurring during particular periods of the complex NAA recovery process, coincident with the so called window of brain vulnerability.

Notes

Acknowledgments

This work was done at The Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome, Rome, Italy and The Neuropharmacology and Neurobiology Section, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom. This work was supported in part by research funds of the University of Catania, University of Rome Tor Vergata and Catholic University of Rome.

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Authors and Affiliations

  • Valentina Di Pietro
    • 1
  • Angela Maria Amorini
    • 2
  • Barbara Tavazzi
    • 2
  • Roberto Vagnozzi
    • 3
  • Ann Logan
    • 1
  • Giacomo Lazzarino
    • 2
  • Stefano Signoretti
    • 4
  • Giuseppe Lazzarino
    • 5
  • Antonio Belli
    • 1
  1. 1.Neuropharmacology and Neurobiology Section, School of Clinical and Experimental Medicine, College of Medical and Dental SciencesUniversity of BirminghamBirminghamUK
  2. 2.Institute of Biochemistry and Clinical BiochemistryCatholic University of RomeRomeItaly
  3. 3.Department of Biomedicine and Prevention, Section of NeurosurgeryUniversity of Rome Tor VergataRomeItaly
  4. 4.Division of Neurosurgery, Department of Neurosciences Head and Neck SurgerySan Camillo HospitalRomeItaly
  5. 5.Department of Biology, Geology and Environmental Sciences, Division of Biochemistry and Molecular BiologyUniversity of CataniaCataniaItaly

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