Die Bedeutung von Neuregulin im 6-OHDA Tiermodell der Parkinson Krankheit
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Philipps-Universität Marburg
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Abstract
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.
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Dates
Created: 2014Issued: 2014-11-05Updated: 2014-11-05
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
Keywords
Parkinson Disease
DFG-subjects
Parkinsonkrankheit
DDC-Numbers
610
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Schindler, Friederike Rebecca (1060348071): Die Bedeutung von Neuregulin im 6-OHDA Tiermodell der Parkinson Krankheit. : Philipps-Universität Marburg 2014-11-05. DOI: https://doi.org/10.17192/z2014.0700.
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This item has been published with the following license: In Copyright