title: The molecular mechanisms affecting N-acetylaspartate homeostasis following experimental graded traumatic brain injury.
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.
authors: Neuropharmacology and Neurobiology Section, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
authors: Valentina
authors: V
authors: Di Pietro
authors: Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome, Rome, Italy.
authors: Angela Maria
authors: AM
authors: Amorini
authors: Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome, Rome, Italy.
authors: Barbara
authors: B
authors: Tavazzi
authors: Department of Biomedicine and Prevention, Section of Neurosurgery, University of Rome Tor Vergata, Rome, Italy.
authors: Roberto
authors: R
authors: Vagnozzi
authors: Neuropharmacology and Neurobiology Section, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
authors: Ann
authors: A
authors: Logan
authors: Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome, Rome, Italy.
authors: Giacomo
authors: G
authors: Lazzarino
authors: Division of Neurosurgery, Department of Neurosciences Head and Neck Surgery, San Camillo Hospital, Rome, Italy.
authors: Stefano
authors: S
authors: Signoretti
authors: Department of Biology, Geology and Environmental Sciences, Division of Biochemistry and Molecular Biology, University of Catania, Catania, Italy.
authors: Giuseppe
authors: G
authors: Lazzarino
authors: Neuropharmacology and Neurobiology Section, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
authors: Antonio
authors: A
authors: Belli
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001224:Aspartic Acid; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; C000179:N-acetylaspartate; D000123:Acetyltransferases; D000581:Amidohydrolases; C019751:aspartoacylase