Frontal dopaminergic abnormality in Tourette syndrome: a postmortem analysis.
Frontal-subcortical abnormalities have been implicated in the pathophysiology of Tourette syndrome (TS). The goal of this study was to more extensively evaluate a possible underlying neurochemical abnormality in frontal cortex. Postmortem brain tissue from frontal and occipital regions (Brodmann's areas 4, 6, 9, 10, 11, 12, and 17) from three TS patients and three age-and sex-matched controls were analyzed by semiquantitative immunoblotting. Relative densities were measured for a variety of neurochemical markers including dopamine (D1, D2), serotonin (5HT-1A), and alpha-adrenergic (alpha-2A) receptors, the dopamine transporter (DAT), a monoamine terminal marker (vesicular monoamine transporter type 2, VMAT-2), and vesicular docking and release proteins (VAMP-2, synaptotagmin, SNAP-25, syntaxin, synaptophysin). Data from each TS sample, corrected for actin content, was expressed as a percentage value of its control. Results identified consistent increases of DAT and D2 receptor density in five of six frontal regions in all three TS subjects. D1 and alpha-2A receptor density were increased in a few frontal regions. These results support the hypothesis of a dopaminergic dysfunction in the frontal lobe and a likely role in the pathophysiology of TS.
Yoon
Dustin Y
DY
Department of Neurology, Johns Hopkins University School of Medicine, Harriett Lane Outpatient Building, 200 N. Wolfe Street, Suite 2158, Baltimore, MD 21205, USA.
Gause
Colin D
CD
Leckman
James F
JF
Singer
Harvey S
HS
D000328:Adult; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001923:Brain Chemistry / Q000502:physiology; D004298:Dopamine / Q000032:analysis / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000032:analysis / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism; D011237:Predictive Value of Tests; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000473:pathology*; D017448:Receptors, Dopamine D2 / Q000032:analysis / Q000378:metabolism; D012016:Reference Values; D013570:Synaptic Membranes / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism; D005879:Tourette Syndrome / Q000378:metabolism* / Q000473:pathology*; D015854:Up-Regulation / Q000502:physiology
D015415:Biomarkers; D050483:Dopamine Plasma Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017448:Receptors, Dopamine D2; D004298:Dopamine