Dopamine transporter and nitric oxide synthase in hypoxic-ischemic brain.
Changes in dopamine transporter and neuronal nitric oxide synthase (nNOS) were investigated by immunohistochemistry in 18 cases of hypoxic-ischemic basal ganglia necrosis. Neuropil dopamine transporter immunostaining in the striatum was increased in seven cases, with relatively mild basal ganglia necrosis, and decreased in four cases, with marked basal ganglia necrosis, compared with age-matched control subjects. Correspondingly, some striatal neurons had increased immunoreactivity to dopamine transporter in the cases of increased immunostaining in the neuropil. nNOS-positive neurons did not obviously change in cases of basal ganglia necrosis within 2 days after birth and then decreased or were not detectable in cases of basal ganglia necrosis at more than 3 days after birth. The results suggest that the synthesis of dopamine transporter is up-regulated in relatively mild basal ganglia necrosis to compensate for the uptake of increased dopamine, that this compensative ability is lost in marked basal ganglia necrosis, and that nNOS-containing neurons in the striatum are relatively resistant to hypoxic ischemia. We speculate that glutamate excitotoxicity mediated by glutamate receptors 1, 2/3, and 4 and excessive dopaminergic excitatory activity may play important roles in hypoxic-ischemic basal ganglia necrosis and that nNOS does not contribute to that condition.
Meng
S Z
SZ
Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
Ohyu
J
J
Itoh
M
M
Takashima
S
S
D001480:Basal Ganglia Diseases / Q000201:enzymology / Q000473:pathology*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism*; D016022:Case-Control Studies; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000201:enzymology / Q000378:metabolism*; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000201:enzymology* / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009336:Necrosis; D017072:Neostriatum / Q000473:pathology; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D015854:Up-Regulation
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D019001:Nitric Oxide Synthase; D004298:Dopamine