Neonatal hypoxic-ischemic or excitotoxic striatal injury results in a decreased adult number of substantia nigra neurons.
It has been shown that morphologic and biochemical presynaptic markers of dopaminergic terminals are preserved in a unilateral experimental model of neonatal hypoxic-ischemic injury to the striatum. As the substantia nigra is spared direct injury in this model, we anticipated that the number of tyrosine hydroxylase-positive dopaminergic neurons projecting to the striatum would also be normal. We have found, however, that following unilateral neonatal striatal injury the number of ipsilateral tyrosine hydroxylase-positive neurons is decreased, as is the mean area of the substantia nigra pars compacta. The decrease in neurons is correlated with the decrease in striatal size (r = 0.7, P = 0.01). Neuron loss is most pronounced in the substantia nigra pars reticulata, where it is 50%. Calbindin-positive neurons in the dorsal tier of the substantia nigra pars compacta appear to be preserved. We also examined effects on the nigra following a neonatal excitotoxic striatal lesion made with quinolinic acid. We observed a decrease in the number of substantia nigra tyrosine hydroxylase-positive neurons in the absence of direct nigral injury, and the decrease was closely correlated with reductions in striatal area (r = 0.91, p < 0.01). While there are a number of possible explanations for these observations, one major possibility is that there has been a reduction in tyrosine hydroxylase-positive neurons due to a diminution in developmental target-derived trophic support from the striatum. If striatum-derived trophic support plays a role in the developmental regulation of substantia nigra neuron number, then abnormalities in this supportive relationship may play a role in the loss of these neurons in some animal models of developmental nigral degeneration, and some forms of human parkinsonism.
Burke
R E
RE
Department of Neurology, Columbia University, New York, NY 10032.
Macaya
A
A
DeVivo
D
D
Kenyon
N
N
Janec
E M
EM
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D064026:Calbindins; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000502:physiology; D002534:Hypoxia, Brain / Q000378:metabolism*; D007150:Immunohistochemistry; D009474:Neurons / Q000201:enzymology; D017378:Quinolinic Acid / Q000633:toxicity; D051381:Rats; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D064026:Calbindins; D064030:S100 Calcium Binding Protein G; D014446:Tyrosine 3-Monooxygenase; D017378:Quinolinic Acid; D004298:Dopamine