title: Protein Markers of Neurotransmitter Synthesis and Release in Postmortem Schizophrenia Substantia Nigra.
abstract: The substantia nigra (SN) provides the largest dopaminergic input to the brain, projects to the striatum (the primary locus of action for antipsychotic medication), and receives GABAergic and glutamatergic inputs. This study used western blot analysis to compare protein levels of tyrosine hydroxylase (TH), glutamate decarboxylase (GAD67), and vesicular glutamate transporters (vGLUT1 and vGLUT2) in postmortem human SN in schizophrenia subjects (n=13) and matched controls (n=12). As a preliminary analysis, the schizophrenia group was subdivided by (1) treatment status: off medication (n=4) or on medication (n=9); or (2) treatment response: treatment resistant (n=5) or treatment responsive (n=4). The combined schizophrenia group had higher TH and GAD67 protein levels than controls (an increase of 69.6%, P=0.01 and 19.5%, P=0.004, respectively). When subdivided by medication status, these increases were found in the on-medication subjects (TH 88.3%, P=0.008; GAD67 40.6%, P=0.003). In contrast, unmedicated schizophrenia subjects had higher vGLUT2 levels than controls (an increase of 28.7%, P=0.041), but vGLUT2 levels were similar between medicated schizophrenia subjects and controls. Treatment-resistant subjects had significantly higher TH and GAD67 levels than controls (an increase of 121.0%, P=0.0003 and 58.7%, P=0.004, respectively). These data suggest increases in dopamine and GABA transmission in the SN in schizophrenia, with a potential relation to treatment and response.
authors.affiliation: Department of Psychology and Behavioral Neuroscience, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Kirsten E
authors.initials: KE
authors.lastname: Schoonover
authors.affiliation: Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Lesley A
authors.initials: LA
authors.lastname: McCollum
authors.affiliation: Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Rosalinda C
authors.initials: RC
authors.lastname: Roberts
mesh_terms: D004298:Dopamine / Q000096:biosynthesis; D005260:Female; D005968:Glutamate Decarboxylase / Q000032:analysis* / Q000378:metabolism; D018698:Glutamic Acid / Q000096:biosynthesis; D006801:Humans; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism*; D013378:Substantia Nigra / Q000737:chemistry* / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis* / Q000378:metabolism; D050598:Vesicular Glutamate Transport Protein 1 / Q000032:analysis* / Q000378:metabolism; D050599:Vesicular Glutamate Transport Protein 2 / Q000032:analysis* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis
chemical_list: C493476:SLC17A6 protein, human; C493464:SLC17A7 protein, human; D050598:Vesicular Glutamate Transport Protein 1; D050599:Vesicular Glutamate Transport Protein 2; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D014446:Tyrosine 3-Monooxygenase; D005968:Glutamate Decarboxylase; D004298:Dopamine