Die Bedeutung von Neuregulin im 6-OHDA Tiermodell der Parkinson Krankheit

The present study shows that intraperitoneal injection of Neuregulin1-β1 protects dopaminergic nigral neurons against cell death. This was shown in the 6- hydroxydopamine (6-OHDA)-model, one of the most important animal-models of idiopathic Parkinson’s disease (IPS). 6-OHDA was unilaterally injected into the striatum in mice, which induced a retrograde degeneration of nigral dopaminergic cells, so on injection-side a reduced number of cells (expressed in percentage of the contralateral intact side) of 35.3% ± 2.3% was observed (group 6 – P). Animals, which received Neuregulin1-β1 injection immediately (starting 6 hours post operation = group 6 – N), showed a cell number on the leasioned side of 61.3% ± 3.0% and animals, which received Neuregulin1-β1 treatment delayed (starting 48 hours post operation = group 6 – vN), showed 59.6% ± 6.0%. These results were statistically relevant in both Neuregulin1-β1 treated groups (p < 0.001). In sham-operated animals a higher cell number (5468.3 ± 53.7) was observed after intraperitoneal injection of Neuregulin1-β1 in comparison to not Neuregulin1-β1 treated sham-operated animals (4686.0 ± 51.1; control group). This effect could be explained by induction of a dopaminergic phenotype in preexisting cells. In order to exclude, that the Neuregulin1-β1 effect is a mere consequence of this induction, we expressed the cell numbers as percentage of the contralateral intact side. All shown results were confirmed in another staining. Addiotinal results demonstrate Neuregulin1-β1 protected significantly (p < 0.001) against loss of striatal dopaminergic fibers (75.2% ± 5.6% striatal density in group 6 – N; 48.0% ± 4.7% in group 6 - P). Consistent with the histological findings Neuregulin1- β1 treatment reduced 6-OHDA-associated rotational behaviour. Neuregulin1-β1 untreated animals showed 2.4 ± 0,6 rotations per minute. In group 6 – N 1.1 ± 0.6 rotations per minute were observed, which was no significantly different to 0.4 ± 0.2 rotations in controls. Delayed Neuregulin1-β1 treatment features no statistically relevant effect (1.9 ± 0.4 rotations per minute). Current therapy of IPS is based on symptomatic improvement, and neuroprotective therapy is not available. Due to this circumstance it is important to develop neuroprotective therapy strategies. Neuregulin1-β1 is the only known neuroprotective neurotrophine that passes the blood brain barrier upon systemic application. In this study potent neuroprotective effects of Neuregulin1-β1 treatment on the nigrostriatal dopaminergic system were demonstrated.