%0 Journal Article
%A Wedekind, Franziska
%A Oskamp, Angela
%A Lang, Markus
%A Hawlitschka, Alexander
%A Zilles, Karl
%A Wree, Andreas
%A Bauer, Andreas
%T Intrastriatal administration of botulinum neurotoxin A normalizes striatal D$_{2}$R binding and reduces striatal D$_{1}$R binding in male hemiparkinsonian rats
%J Journal of neuroscience research
%V 96
%N 1
%@ 0360-4012
%C New York, NY [u.a.]
%I Wiley-Liss
%M FZJ-2017-05301
%P 75–86
%D 2018
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:28695985
%U <Go to ISI:>//WOS:000425811000009
%R 10.1002/jnr.24110
%U https://juser.fz-juelich.de/record/836178