title: Neurotransmitter and their metabolite concentrations in different areas of the HPRT knockout mouse brain.
abstract: Lesch-Nyhan syndrome (LNS) is characterized by uric acid overproduction and severe neurobehavioral symptoms, such as recurrent self-mutilative behavior. To learn more about the pathophysiology of the disease, we quantified neurotransmitters and their metabolites in the cerebral hemisphere, cerebellum and the medulla oblongata of HPRT knockout mice, an animal model for LNS, in comparison to the corresponding wild-type. Our analyses included l-glutamate, 4-aminobutanoic acid (GABA), acetylcholine, serotonin, 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine, l-normetanephrine, epinephrine and l-metanephrine and were conducted via high performance liquid chromatography (HPLC) coupled to tandem mass spectrometry (MS/MS). Among these neurotransmitter systems, we did not find any abnormalities in the HPRT knockout mouse brains. On one side, this might indicate that HPRT deficiency most severely affects dopamine signaling, while brain functioning based on other neurotransmitters is more or less spared. On the other hand, our findings may reflect a compensating mechanism for impaired purine salvage that protects the brain in HPRT-deficient mice but not in LNS patients.
authors.affiliation: Institute of Pharmacology, Hannover Medical School, Hannover, Germany. Electronic address: tschirner.sarah@mh-hannover.de.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Tschirner
authors.affiliation: Research Core Unit Metabolomics, Hannover Medical School, Hannover, Germany. Electronic address: gutzki.frank@mh-hannover.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Gutzki
authors.affiliation: Institute of Pharmacology, Hannover Medical School, Hannover, Germany. Electronic address: schneider.erich@mh-hannover.de.
authors.forename: Erich H
authors.initials: EH
authors.lastname: Schneider
authors.affiliation: Institute of Pharmacology, Hannover Medical School, Hannover, Germany. Electronic address: seifert.roland@mh-hannover.de.
authors.forename: Roland
authors.initials: R
authors.lastname: Seifert
authors.affiliation: Institute of Pharmacology, Hannover Medical School, Hannover, Germany; Research Core Unit Metabolomics, Hannover Medical School, Hannover, Germany. Electronic address: kaever.volkhard@mh-hannover.de.
authors.forename: Volkhard
authors.initials: V
authors.lastname: Kaever
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005786:Gene Expression Regulation / Q000235:genetics*; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018377:Neurotransmitter Agents / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D018377:Neurotransmitter Agents; D007041:Hypoxanthine Phosphoribosyltransferase
keywords: HPLC; HPRT knockout mice; Lesch–Nyhan syndrome; Mass spectrometry; Neurotransmitters