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[(18)F]fallypride-PET/CT Analysis of the Dopamine D(2)/D(3) Receptor in the Hemiparkinsonian Rat Brain Following Intrastriatal Botulinum Neurotoxin A Injection

Intrastriatal injection of botulinum neurotoxin A (BoNT-A) results in improved motor behavior of hemiparkinsonian (hemi-PD) rats, an animal model for Parkinson’s disease. The caudate–putamen (CPu), as the main input nucleus of the basal ganglia loop, is fundamentally involved in motor function and d...

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Autores principales: Mann, Teresa, Kurth, Jens, Hawlitschka, Alexander, Stenzel, Jan, Lindner, Tobias, Polei, Stefan, Hohn, Alexander, Krause, Bernd J., Wree, Andreas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017015/
https://www.ncbi.nlm.nih.gov/pubmed/29509680
http://dx.doi.org/10.3390/molecules23030587
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author Mann, Teresa
Kurth, Jens
Hawlitschka, Alexander
Stenzel, Jan
Lindner, Tobias
Polei, Stefan
Hohn, Alexander
Krause, Bernd J.
Wree, Andreas
author_facet Mann, Teresa
Kurth, Jens
Hawlitschka, Alexander
Stenzel, Jan
Lindner, Tobias
Polei, Stefan
Hohn, Alexander
Krause, Bernd J.
Wree, Andreas
author_sort Mann, Teresa
collection PubMed
description Intrastriatal injection of botulinum neurotoxin A (BoNT-A) results in improved motor behavior of hemiparkinsonian (hemi-PD) rats, an animal model for Parkinson’s disease. The caudate–putamen (CPu), as the main input nucleus of the basal ganglia loop, is fundamentally involved in motor function and directly interacts with the dopaminergic system. To determine receptor-mediated explanations for the BoNT-A effect, we analyzed the dopamine D(2)/D(3) receptor (D(2)/D(3)R) in the CPu of 6-hydroxydopamine (6-OHDA)-induced hemi-PD rats by [(18)F]fallypride-PET/CT scans one, three, and six months post-BoNT-A or -sham-BoNT-A injection. Male Wistar rats were assigned to three different groups: controls, sham-injected hemi-PD rats, and BoNT-A-injected hemi-PD rats. Disease-specific motor impairment was verified by apomorphine and amphetamine rotation testing. Animal-specific magnetic resonance imaging was performed for co-registration and anatomical reference. PET quantification was achieved using PMOD software with the simplified reference tissue model 2. Hemi-PD rats exhibited a constant increase of 23% in D(2)/D(3)R availability in the CPu, which was almost normalized by intrastriatal application of BoNT-A. Importantly, the BoNT-A effect on striatal D(2)/D(3)R significantly correlated with behavioral results in the apomorphine rotation test. Our results suggest a therapeutic effect of BoNT-A on the impaired motor behavior of hemi-PD rats by reducing interhemispheric changes of striatal D(2)/D(3)R.
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spelling pubmed-60170152018-11-13 [(18)F]fallypride-PET/CT Analysis of the Dopamine D(2)/D(3) Receptor in the Hemiparkinsonian Rat Brain Following Intrastriatal Botulinum Neurotoxin A Injection Mann, Teresa Kurth, Jens Hawlitschka, Alexander Stenzel, Jan Lindner, Tobias Polei, Stefan Hohn, Alexander Krause, Bernd J. Wree, Andreas Molecules Article Intrastriatal injection of botulinum neurotoxin A (BoNT-A) results in improved motor behavior of hemiparkinsonian (hemi-PD) rats, an animal model for Parkinson’s disease. The caudate–putamen (CPu), as the main input nucleus of the basal ganglia loop, is fundamentally involved in motor function and directly interacts with the dopaminergic system. To determine receptor-mediated explanations for the BoNT-A effect, we analyzed the dopamine D(2)/D(3) receptor (D(2)/D(3)R) in the CPu of 6-hydroxydopamine (6-OHDA)-induced hemi-PD rats by [(18)F]fallypride-PET/CT scans one, three, and six months post-BoNT-A or -sham-BoNT-A injection. Male Wistar rats were assigned to three different groups: controls, sham-injected hemi-PD rats, and BoNT-A-injected hemi-PD rats. Disease-specific motor impairment was verified by apomorphine and amphetamine rotation testing. Animal-specific magnetic resonance imaging was performed for co-registration and anatomical reference. PET quantification was achieved using PMOD software with the simplified reference tissue model 2. Hemi-PD rats exhibited a constant increase of 23% in D(2)/D(3)R availability in the CPu, which was almost normalized by intrastriatal application of BoNT-A. Importantly, the BoNT-A effect on striatal D(2)/D(3)R significantly correlated with behavioral results in the apomorphine rotation test. Our results suggest a therapeutic effect of BoNT-A on the impaired motor behavior of hemi-PD rats by reducing interhemispheric changes of striatal D(2)/D(3)R. MDPI 2018-03-06 /pmc/articles/PMC6017015/ /pubmed/29509680 http://dx.doi.org/10.3390/molecules23030587 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mann, Teresa
Kurth, Jens
Hawlitschka, Alexander
Stenzel, Jan
Lindner, Tobias
Polei, Stefan
Hohn, Alexander
Krause, Bernd J.
Wree, Andreas
[(18)F]fallypride-PET/CT Analysis of the Dopamine D(2)/D(3) Receptor in the Hemiparkinsonian Rat Brain Following Intrastriatal Botulinum Neurotoxin A Injection
title [(18)F]fallypride-PET/CT Analysis of the Dopamine D(2)/D(3) Receptor in the Hemiparkinsonian Rat Brain Following Intrastriatal Botulinum Neurotoxin A Injection
title_full [(18)F]fallypride-PET/CT Analysis of the Dopamine D(2)/D(3) Receptor in the Hemiparkinsonian Rat Brain Following Intrastriatal Botulinum Neurotoxin A Injection
title_fullStr [(18)F]fallypride-PET/CT Analysis of the Dopamine D(2)/D(3) Receptor in the Hemiparkinsonian Rat Brain Following Intrastriatal Botulinum Neurotoxin A Injection
title_full_unstemmed [(18)F]fallypride-PET/CT Analysis of the Dopamine D(2)/D(3) Receptor in the Hemiparkinsonian Rat Brain Following Intrastriatal Botulinum Neurotoxin A Injection
title_short [(18)F]fallypride-PET/CT Analysis of the Dopamine D(2)/D(3) Receptor in the Hemiparkinsonian Rat Brain Following Intrastriatal Botulinum Neurotoxin A Injection
title_sort [(18)f]fallypride-pet/ct analysis of the dopamine d(2)/d(3) receptor in the hemiparkinsonian rat brain following intrastriatal botulinum neurotoxin a injection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017015/
https://www.ncbi.nlm.nih.gov/pubmed/29509680
http://dx.doi.org/10.3390/molecules23030587
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