Publication Database

Moderate degeneration of nigral neurons after repeated but not after single intrastriatal injections of low doses of 6-hydroxydopamine in mice (2008)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Richter, Franziska

Hamann, Melanie

Richter, Angelika

Quelle

Brain research

Bandzählung: 1188

Seiten: 148 – 156

ISSN: 0006-8993

Sprache

Englisch

Verweise

Pubmed: 18035334

Kontakt

Institut für Pharmakologie und Toxikologie

Koserstr. 20
14195 Berlin
+49 30 838 53221
pharmakologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.