Striatal monoamine neurotransmitters and metabolites in dominantly inherited olivopontocerebellar atrophy.
We measured the levels of the monoamine neurotransmitters and metabolites in striatum of 14 patients with end-stage dominantly inherited olivopontocerebellar atrophy (OPCA). On average, dopamine levels were reduced in putamen (-53%), caudate (-35%), and nucleus accumbens (-31%). However, individual patient values showed a wide variation, indicating that mild to moderate striatal dopamine loss is a common but not constant feature of OPCA. Seven patients had marked putamen dopamine loss (-62% to -81%) but without evidence of correspondingly severe substantia nigra cell damage; this suggests the possibility of a "dying-back" phenomenon in which nerve terminal loss precedes cell body degeneration. Severe substantia nigra cell loss with almost total (-95% to -99%) putamen and caudate dopamine depletion was present in two patients; however, none of the 14 patients had had a clinical diagnosis of parkinsonism or was receiving antiparkinsonian medication. Mean striatal serotonin levels were normal, whereas concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid were elevated by 47% to 63%; this suggests increased activity of raphe dorsalis serotonin neurons innervating the striatum, which might aggravate the functional consequences of the dopamine deficit.
Kish
S J
SJ
Human Neurochemical Pathology Lab, Clarke Institute of Psychiatry, Toronto, ON, Canada.
Robitaille
Y
Y
el-Awar
M
M
Clark
B
B
Schut
L
L
Ball
M J
MJ
Young
L T
LT
Currier
R
R
Shannak
K
K
D001679:Biogenic Amines / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D005799:Genes, Dominant; D006801:Humans; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009849:Olivopontocerebellar Atrophies / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013378:Substantia Nigra / Q000473:pathology
D001679:Biogenic Amines; D018377:Neurotransmitter Agents; D004298:Dopamine