This title appears in the Scientific Report :
2017
Please use the identifier:
http://dx.doi.org/10.1002/jnr.24110 in citations.
Intrastriatal administration of botulinum neurotoxin A normalizes striatal D$_{2}$R binding and reduces striatal D$_{1}$R binding in male hemiparkinsonian rats
Intrastriatal administration of botulinum neurotoxin A normalizes striatal D$_{2}$R binding and reduces striatal D$_{1}$R binding in male hemiparkinsonian rats
Cerebral administration of botulinum neurotoxin A (BoNT-A) has been shown to improve disease-specific motor behavior in a rat model of Parkinson disease (PD). Since the dopaminergic system of the basal ganglia fundamentally contributes to motor function, we investigated the impact of BoNT-A on stria...
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Personal Name(s): | Wedekind, Franziska (Corresponding author) |
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Oskamp, Angela / Lang, Markus / Hawlitschka, Alexander / Zilles, Karl / Wree, Andreas / Bauer, Andreas | |
Contributing Institute: |
Nuklearchemie; INM-5 Strukturelle und funktionelle Organisation des Gehirns; INM-1 Molekulare Organisation des Gehirns; INM-2 |
Published in: | Journal of neuroscience research, 96 (2018) 1, S. 75–86 |
Imprint: |
New York, NY [u.a.]
Wiley-Liss
2018
|
PubMed ID: |
28695985 |
DOI: |
10.1002/jnr.24110 |
Document Type: |
Journal Article |
Research Program: |
Connectivity and Activity |
Publikationsportal JuSER |
Cerebral administration of botulinum neurotoxin A (BoNT-A) has been shown to improve disease-specific motor behavior in a rat model of Parkinson disease (PD). Since the dopaminergic system of the basal ganglia fundamentally contributes to motor function, we investigated the impact of BoNT-A on striatal dopamine receptor expression using in vitro and in vivo imaging techniques (positron emission tomography and quantitative autoradiography, respectively). Seventeen male Wistar rats were unilaterally lesioned with 6-hydroxydopamine (6-OHDA) and assigned to two treatment groups 7 weeks later: 10 rats were treated ipsilaterally with an intrastriatal injection of 1 ng BoNT-A, while the others received vehicle (n = 7). All animals were tested for asymmetric motor behavior (apomorphine-induced rotations and forelimb usage) and for striatal expression of dopamine receptors and transporters (D1 R, D2 R, and DAT). The striatal D2 R availability was also quantified longitudinally (1.5, 3, and 5 months after intervention) in 5 animals per treatment group. The 6-OHDA lesion alone induced a unilateral PD-like phenotype and a 13% increase of striatal D2 R. BoNT-A treatment reduced the asymmetry in both apomorphine-induced rotational behavior and D2 R expression, with the latter returning to normal values 5 months after intervention. D1 R expression was significantly reduced, while DAT concentrations showed no alteration. Independent of the treatment, higher interhemispheric symmetry in raclopride binding to D2 R was generally associated with reduced forelimb akinesia. Our findings indicate that striatal BoNT-A treatment diminishes motor impairment and induces changes in D1 and D2 binding site density in the 6-OHDA rat model of PD. |