Moderate degeneration of nigral neurons after repeated but not after single intrastriatal injections of low doses of 6-hydroxydopamine in mice.
Parkinson's disease (PD) is characterized by a bilateral progressive degeneration of nigrostriatal dopaminergic neurons. Among several toxin-induced animal models of PD, a single intrastriatal injection of 6-hydroxydopamine (6-OHDA) has been reported to provoke a retrograde degeneration of nigral dopaminergic neurons and may reflect an early stage of PD. However, the lack of a progressive neuronal loss in those acute models limits the suitability for the assessment of neuroprotective therapeutics. Therefore, we investigated if repeated microinjections of 6-OHDA into the striatum of mice may generate a subchronic model with progressive degeneration. In contrast to acute bilateral microinjections of 8 microg 6-OHDA, repeated daily intrastriatal applications for 5 d provoked a moderate, but significant loss of nigral neurons. However, a longer treatment over 7 d failed to cause a more marked degeneration than observed after 5 d. Motor performance was unaltered after single and repeated treatments, except of a slight cataleptic behavior and shortened stride-length performance in mice treated over 7 d. The present data show for the first time that daily intrastriatal injections of 6-OHDA over 5 d can enhance the nigrostriatal neurodegeneration in mice. However, the extent of the neuronal loss was moderate and the technical expense limits the utility as a subchronic model.
Institute of Pharmacology and Toxicology, Department of Veterinary Medicine, Freie Universität Berlin, Koserstr. 20, Berlin, Germany. richter.franziska@vetmed.fu-berlin.de
Franziska
F
Richter
Melanie
M
Hamann
Angelika
A
Richter
D000818:Animals; D002452:Cell Count; D004195:Disease Models, Animal; D018450:Disease Progression; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D009498:Neurotoxins / Q000633:toxicity; D016627:Oxidopamine / Q000633:toxicity*; D020734:Parkinsonian Disorders / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D013565:Sympatholytics / Q000633:toxicity; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D009498:Neurotoxins; D013565:Sympatholytics; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine