TY  - JOUR
AU  - Wedekind, Franziska
AU  - Oskamp, Angela
AU  - Lang, Markus
AU  - Hawlitschka, Alexander
AU  - Zilles, Karl
AU  - Wree, Andreas
AU  - Bauer, Andreas
TI  - Intrastriatal administration of botulinum neurotoxin A normalizes striatal D$_{2}$R binding and reduces striatal D$_{1}$R binding in male hemiparkinsonian rats
JO  - Journal of neuroscience research
VL  - 96
IS  - 1
SN  - 0360-4012
CY  - New York, NY [u.a.]
PB  - Wiley-Liss
M1  - FZJ-2017-05301
SP  - 75–86
PY  - 2018
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:28695985
UR  - <Go to ISI:>//WOS:000425811000009
DO  - DOI:10.1002/jnr.24110
UR  - https://juser.fz-juelich.de/record/836178
ER  -