De - und Remyelinisierung in Dopaminrezeptor-defizienten Mäusen

De-and remyelination in dopamine receptor-deficient mice

von Katharina Schultz
Dissertation
Datum der mündl. Prüfung:2012-06-27
Erschienen:2012-05-31
Betreuer:Prof. Dr. Christine Stadelmann-Nessler
Gutachter:Prof. Dr. Christine Stadelmann-Nessler
Gutachter:Prof. Dr. Mikael Simons
Gutachter:Prof. Dr. David Liebetanz
Zum Verlinken/Zitieren: http://dx.doi.org/10.53846/goediss-1535

 

 

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De-and remyelination in dopamine receptor-deficient mice Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous-system with destruction of myelin sheaths, axonal damage and only partial remyelination. In non remyelinated MS lesions there is often a significant loss of oligodendrocytes. The destruction of oligodendrocytes happens predominantly at the beginning a lesion occurs. In this work the effect of the dopamine D2 receptor (DRD2) and D3 (DRD3) and dopamine agonist pramipexole relating to the oligodendroglial survival in the model of cuprizone-induced demyelination has been tested for toxicity. The literature has shown the expression of DRD2 and DRD3 on oligodendrocyte percusor cells (OPCs) and an effect on the extent of concentration of oligodendrocytes. Our hypothesis is that dopamine receptor-deficient mice compared to wild type (wt) mice have shown an increased vulnerability of oligodendrocytes. Furthermore, it should be investigated how far the therapy with pramipexole, a dopamine D3 receptor agonist, receptor-independent or dependent, leads to a protection of oligodendrocytes. With the help of various histological and immunohistochemical methods we were allowed to count the density of apoptotic oligodendrocytes and activated microglia, which drew conclusions from the extent of tissue damage. We could not find significant differences in the density of apoptotic oligodendrocytes and activated microglia between the different experimental groups. In one experiment, more apoptotic oligodendrocytes were found in the animals of the wild-type PBS (phosphate buffered saline) group compared with the pramipexole-treated DRD3 knockout mice, which may allow to draw conclusions from receptor-independent effects of pramipexole. These results must be reproduced in further studies in detail and will have to be verified. So it appears that endogenous dopamine receptor system plays no significant role in our results - the protection of oligodendrocytes in cuprizone-induced damage. Furthermore, a preventive-protective effect of pramipexole can
Keywords: muliple sclerosis - neuropathology - dopamine receptor deficiency - pramipexole - oligodendrocyte percusor cells OPCs
Schlagwörter: Multiple Sklerose - Neuropathologie - Dopaminrezeptordefizienz - Pramipexol - Oligodendrocytenvorläuferzellen OPCs
 
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