Effect of intrastriatal 6-OHDA lesion on dopaminergic innervation of the rat cortex and globus pallidus.
The present study examined in the rat the effect of a partial lesion of the nigrostriatal dopaminergic pathway induced by intrastriatal injection of 6-hydroxydopamine (6-OHDA), on the dopaminergic innervation of the cortex and the globus pallidus as revealed using tyrosine hydroxylase (TH) immunoreactivity. Twenty-eight days after unilateral injection of 6-OHDA into the dorsal part of the striatum, TH-positive fiber density was reduced by 41% in the dorsal and central part of the structure, and was accompanied by a retrograde loss of 33% of TH-positive neurons in the substantia nigra (SN), while the ventral tegmental area was completely spared. In the SN, TH-positive cell loss was most severe in the ventral part of the structure (-55%). In the same animals, a substantial loss of TH-positive fibers was evident in the dorsal part of the globus pallidus, and involved both thick fibers of passage and thin varicose terminal axonal branches. In the cortex, a loss of TH-positive fibers was prominent in the cingulate area, moderate in the motor area and less affected in the insular area, while the noradrenergic innervation revealed using dopamine-beta-hydroxylase immunoreactivity was preserved in all of these cortical subregions. These results demonstrate that the intrastriatal 6-OHDA lesion model in rats produces a significant loss of dopaminergic axons in extrastriatal structures including the pallidum and cortex, which may contribute to functional sequelae in this animal model of Parkinson's disease.
Debeir
Thomas
T
INSERM U679, Neurologie et Thérapeutique Expérimentale, Hôpital de la Salpêtrière, 47 Boulevard de l'Hôpital, 75013, Paris, France.
Ginestet
Laure
L
François
Chantal
C
Laurens
Stéphanie
S
Martel
Jean-Claude
JC
Chopin
Philippe
P
Marien
Marc
M
Colpaert
Francis
F
Raisman-Vozari
Rita
R
D018663:Adrenergic Agents / Q000633:toxicity*; D000818:Animals; D002452:Cell Count / Q000379:methods; D002540:Cerebral Cortex / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D007839:Functional Laterality / Q000502:physiology; D005917:Globus Pallidus / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009412:Nerve Fibers / Q000378:metabolism; D009434:Neural Pathways / Q000378:metabolism; D016627:Oxidopamine / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects* / Q000293:injuries / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D018663:Adrenergic Agents; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine