gms | German Medical Science

63rd Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Japanese Neurosurgical Society (JNS)

German Society of Neurosurgery (DGNC)

13 - 16 June 2012, Leipzig

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Minocycline and HIF-1 stabilization promote survival of cultured dopaminergic neurons

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  • N. Porz - Department of Neurosurgery, University Hospital, University of Bern, Switzerland
  • S.D. Santo - Department of Neurosurgery, University Hospital, University of Bern, Switzerland
  • A.D. Ducray - Department of Neurosurgery, University Hospital, University of Bern, Switzerland
  • A. Raabe - Department of Neurosurgery, University Hospital, University of Bern, Switzerland
  • H.R. Widmer - Department of Neurosurgery, University Hospital, University of Bern, Switzerland

Deutsche Gesellschaft für Neurochirurgie. Japanische Gesellschaft für Neurochirurgie. 63. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie (JNS). Leipzig, 13.-16.06.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. DocP 020

doi: 10.3205/12dgnc407, urn:nbn:de:0183-12dgnc4076

Published: June 4, 2012

© 2012 Porz et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Objective: The lack of effective therapies for Parkinson's disease has lead to the necessity to explore novel treatment options. Notably, activation of Hypoxia inducible Factor-1 (HIF-1) is involved in neural progenitor cell propagation and dopaminergic cell differentiation. Moreover, there is increasing evidence that the tetracycline derivate minocycline exerts neuroprotective effects. Aim of the present study was to investigate the effect of HIF-1 activation by chemical stabilization and minocycline treatment on survival of cultured dopaminergic neurons.

Methods: The ventral mesencephalon (VM) was isolated from Wistar rat fetuses (at embryonic day 14) and grown as organotypic free-floating roller tube (FFRT) cultures for one week. HIF-1 activation was induced by dimethyloxallyl glycine (DMOG, [1mM]) incubation starting at day in vitro 2 until the end of the culture period. Minocycline treatment followed the same schedule. Untreated cultures served as controls. The cultures were then fixed, sectioned on a cryostat and the sections were immunohistochemically stained for the dopaminergic cell marker tyrosine hydroxylase (TH) and for the cell proliferation-associated protein Ki-67.

Results: Chronic DMOG and minocycline treatment resulted in a significant increase of TH-positive cells (by 50% and 75%, respectively) as compared to controls. Despite a parallel augmentation of Ki-67 positive cells by DMOG (by 70%) no co-localization between Ki-67 and TH-positive cells was observed.

Conclusions: Our findings suggest that stabilization of HIF-1 and minocycline provide a means to promote differentiation and / or survival of dopaminergic neurons. Moreover, the increased proliferation rate implies that a pool of precursor cells was stimulated by HIF-1 stabilization. These data support previous reports assessing the possible therapeutic utility of HIF-1 induction and minocycline for Parkinson's disease.

This work was supported by the Swiss Parkinson Foundation.