gms | German Medical Science

55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

25. bis 28.04.2004, Köln

Transplantation of rostral migratory stream (RMS)-derived cells into a rat model of Parkinson’s disease

Transplantation von Zellen des rostralen migratorischen Stroms in ein Tiermodell des M. Parkinson

Meeting Abstract

Suche in Medline nach

  • corresponding author Maria-Beatrix Schmidt - Labor für Molekulare Neurochirurgie, Abt. für Funktionelle und Stereotaktische Neurochirurgie, Universitätsklinikum Freiburg, Freiburg
  • I. Singec - Institut für Anatomie und Zellbiologie, Universität Freiburg, Freiburg
  • A. Klein - Labor für Molekulare Neurochirurgie, Abt. für Funktionelle und Stereotaktische Neurochirurgie, Universitätsklinikum Freiburg, Freiburg
  • G. Nikkhah - Labor für Molekulare Neurochirurgie, Abt. für Funktionelle und Stereotaktische Neurochirurgie, Universitätsklinikum Freiburg, Freiburg

Deutsche Gesellschaft für Neurochirurgie. Ungarische Gesellschaft für Neurochirurgie. 55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie. Köln, 25.-28.04.2004. Düsseldorf, Köln: German Medical Science; 2004. DocP 03.26

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2004/04dgnc0309.shtml

Veröffentlicht: 23. April 2004

© 2004 Schmidt et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective

The continuous loss of dopaminergic neurons mainly in the nigrostriatal system lead to the neurodegenerative disorder called Parkinson’s disease (PD). Since promising strategies for treating PD as neurotransplantation of foetal brain tissue pose considerable ethical constraints, therefore is a need for alternative cell resources. One of these sources may be the adult mammalian brain which possesses stem/progenitor cells with the potential of migration and differentiation. Throughout adult life persisting neural stem cells of the subventricular zone (SVZ) and RMS generate neuroblasts which migrate over a long distance and ultimately differentiate into tyrosinhydroxylase positive (TH+) and GABAergic interneurons in the olfactory bulb. The aim of this study was to determine whether the exploitation of neuroblasts of the forebrain might be useful to ameliorate PD symptoms and to restore the dopaminergic system.

Methods

In a short term study (STS) (5 rats) and a long-term study (LTS) (19 rats) all subjects received unilateral stereotactic injections with 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. Another 6 animals served as non-lesioned controls in the LTS. Drug-induced rotation tests were assessed to prove the lesion effect. Additionally, the LTS animals were tested in skilled forelimb behaviour. The RMS of P11 transgenic mice ubiquitously expressing GFP (kras-GFP) were explanted, dissociated, and subsequently transplanted into the striatum of these rats which obtained immunosuppression just before the transplantation and until the perfusion. All the animals were tested again in the rotation tests and the LTS animals performed the skilled forelimb behaviour test. Finally, all animals were perfused and the immunohistology against TH and GFP was analysed.

Results

Histological analysis show GFP positive cells (300-1000 cells per graft) which were widely distributed in the host striatum exhibiting elaborate dendritic arborizations covered by spines, both in the short term as well as in the long-term experiment. TH positive cells (100-600 cells per graft) were found only in the STS, but not in the LTS. In parallel, rotation tests revealed functional improvement only in the STS, but not in the LTS. No effects were seen in the skilled forelimb behaviour.

Conclusions

Therefore, RMS- derived cells seem to be a promising cell source for a cell-based restorative approach in the dopaminergic nigrostriatal system, and potentially also in Parkinson's disease.