Striatal 6-hydroxydopamine induces apoptosis of nigral neurons in the adult rat.
The massive dopaminergic neuronal loss that occurs in Parkinson's disease shows features of apoptosis. In the current study we have characterised the neuronal death in an animal model of Parkinson's disease. 6-Hydroxydopamine infused in the striatum of adult rats induced progressive loss of dopamine neurons, identified as tyrosine hydroxylase immunoreactive profiles, in the ipsilateral substantia nigra starting at day 5 post-lesion (32%). Silver staining revealed the presence of apoptotic profiles with neuronal morphology in the substantia nigra ipsilateral to the intrastriatal 6-hydroxydopamine injection. These apoptotic nuclei were first observed at day 6 post-lesion, peaked between days 7 and 10 and then abruptly declined. The apoptotic morphology of 6-hydroxydopamine-induced neuronal death was confirmed by electron microscopic studies. These data show that intrastriatal 6-hydroxydopamine-induced dopaminergic neuronal death in the adult rat is apoptotic and supports the use of this lesion protocol as an animal model of Parkinson's disease.
Martí
Maria J
MJ
Experimental Neurology Laboratory, Neurological Service, Fundació Clínic, Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer (IDIBAPS), 08036, Barcelona, Spain. mjmarti@clinic.ub.es
Saura
Josep
J
Burke
Robert E
RE
Jackson-Lewis
Vernice
V
Jiménez
Anna
A
Bonastre
Mercé
M
Tolosa
Eduard
E
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002452:Cell Count; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D053938:DNA Fragmentation / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D017072:Neostriatum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D009434:Neural Pathways / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D013565:Sympatholytics; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D013565:Sympatholytics; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine