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.
Human Neurochemical Pathology Lab, Clarke Institute of Psychiatry, Toronto, ON, Canada.
S J
SJ
Kish
Y
Y
Robitaille
M
M
el-Awar
B
B
Clark
L
L
Schut
M J
MJ
Ball
L T
LT
Young
R
R
Currier
K
K
Shannak
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