Cargando…

A Rat Model of Hemidystonia Induced by 3-Nitropropionic Acid

OBJECTIVE: Secondary dystonia commonly presents as hemidystonia and is often refractory to current treatments. We aimed to establish an inducible rat model of hemidystonia utilizing 3-nitropropionic acid (3-NP) and to determine the pathophysiology of this model. METHODS: Two different doses of 3-NP...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Huan-Guang, Ma, Yu, Meng, Da-Wei, Yang, An-Chao, Zhang, Jian-guo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3806852/
https://www.ncbi.nlm.nih.gov/pubmed/24194961
http://dx.doi.org/10.1371/journal.pone.0079199
_version_ 1782288447565725696
author Liu, Huan-Guang
Ma, Yu
Meng, Da-Wei
Yang, An-Chao
Zhang, Jian-guo
author_facet Liu, Huan-Guang
Ma, Yu
Meng, Da-Wei
Yang, An-Chao
Zhang, Jian-guo
author_sort Liu, Huan-Guang
collection PubMed
description OBJECTIVE: Secondary dystonia commonly presents as hemidystonia and is often refractory to current treatments. We aimed to establish an inducible rat model of hemidystonia utilizing 3-nitropropionic acid (3-NP) and to determine the pathophysiology of this model. METHODS: Two different doses of 3-NP were stereotactically administered into the ipsilateral caudate putamen (CPu) of Wistar rats. Behavioral changes and alterations in the neurotransmitter levels in the basal ganglia were analyzed. We also performed an electromyogram, 7.0-T magnetic resonance imaging and transmission electron microscopy examination to determine the pathophysiology of the model. RESULTS: In the CPu region, 3-NP produced mitochondrial cristae rupture, axonal degeneration, increased excitatory synaptic vesicles and necrosis. The extracellular concentrations of excitatory amino acids increased, whereas the inhibitory amino acids decreased in the CPu. Furthermore, an imbalance of neurotransmitters was found in other regions of the basal ganglia with the exception of the external globus pallidus. This study demonstrated that 3-NP administration results in CPu damage, and combined with a neurotransmitter imbalance in the basal ganglia, it produces specific neurobehavioral changes in rats. Right limb (contralateral side of CPu lesion) and trunk dystonic postures, shortened step length and ipsiversive dystonic posturing were observed in these rats. Furthermore, EMG recordings confirmed that co-contraction of the agonist and antagonist muscles could be seen for several seconds in right limbs. CONCLUSIONS: Stereotactic injection of 3-NP into the ipsilateral CPu of rats established an inducible model for hemidystonia. This effect might result from an imbalance of neurotransmitter levels, which induce dysfunctional activity of the basal ganglia mainly via the cortico-striato-GPi direct pathway. Symptoms in this model were present for 1 week. Activation of the cortico-striato-GPe indirect pathway and rebalance of neurotransmitters may lead to recovery. This rat model may be a suitable tool used to understand and further investigate the pathophysiology of dystonia.
format Online
Article
Text
id pubmed-3806852
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-38068522013-11-05 A Rat Model of Hemidystonia Induced by 3-Nitropropionic Acid Liu, Huan-Guang Ma, Yu Meng, Da-Wei Yang, An-Chao Zhang, Jian-guo PLoS One Research Article OBJECTIVE: Secondary dystonia commonly presents as hemidystonia and is often refractory to current treatments. We aimed to establish an inducible rat model of hemidystonia utilizing 3-nitropropionic acid (3-NP) and to determine the pathophysiology of this model. METHODS: Two different doses of 3-NP were stereotactically administered into the ipsilateral caudate putamen (CPu) of Wistar rats. Behavioral changes and alterations in the neurotransmitter levels in the basal ganglia were analyzed. We also performed an electromyogram, 7.0-T magnetic resonance imaging and transmission electron microscopy examination to determine the pathophysiology of the model. RESULTS: In the CPu region, 3-NP produced mitochondrial cristae rupture, axonal degeneration, increased excitatory synaptic vesicles and necrosis. The extracellular concentrations of excitatory amino acids increased, whereas the inhibitory amino acids decreased in the CPu. Furthermore, an imbalance of neurotransmitters was found in other regions of the basal ganglia with the exception of the external globus pallidus. This study demonstrated that 3-NP administration results in CPu damage, and combined with a neurotransmitter imbalance in the basal ganglia, it produces specific neurobehavioral changes in rats. Right limb (contralateral side of CPu lesion) and trunk dystonic postures, shortened step length and ipsiversive dystonic posturing were observed in these rats. Furthermore, EMG recordings confirmed that co-contraction of the agonist and antagonist muscles could be seen for several seconds in right limbs. CONCLUSIONS: Stereotactic injection of 3-NP into the ipsilateral CPu of rats established an inducible model for hemidystonia. This effect might result from an imbalance of neurotransmitter levels, which induce dysfunctional activity of the basal ganglia mainly via the cortico-striato-GPi direct pathway. Symptoms in this model were present for 1 week. Activation of the cortico-striato-GPe indirect pathway and rebalance of neurotransmitters may lead to recovery. This rat model may be a suitable tool used to understand and further investigate the pathophysiology of dystonia. Public Library of Science 2013-10-23 /pmc/articles/PMC3806852/ /pubmed/24194961 http://dx.doi.org/10.1371/journal.pone.0079199 Text en © 2013 Liu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Liu, Huan-Guang
Ma, Yu
Meng, Da-Wei
Yang, An-Chao
Zhang, Jian-guo
A Rat Model of Hemidystonia Induced by 3-Nitropropionic Acid
title A Rat Model of Hemidystonia Induced by 3-Nitropropionic Acid
title_full A Rat Model of Hemidystonia Induced by 3-Nitropropionic Acid
title_fullStr A Rat Model of Hemidystonia Induced by 3-Nitropropionic Acid
title_full_unstemmed A Rat Model of Hemidystonia Induced by 3-Nitropropionic Acid
title_short A Rat Model of Hemidystonia Induced by 3-Nitropropionic Acid
title_sort rat model of hemidystonia induced by 3-nitropropionic acid
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3806852/
https://www.ncbi.nlm.nih.gov/pubmed/24194961
http://dx.doi.org/10.1371/journal.pone.0079199
work_keys_str_mv AT liuhuanguang aratmodelofhemidystoniainducedby3nitropropionicacid
AT mayu aratmodelofhemidystoniainducedby3nitropropionicacid
AT mengdawei aratmodelofhemidystoniainducedby3nitropropionicacid
AT yanganchao aratmodelofhemidystoniainducedby3nitropropionicacid
AT zhangjianguo aratmodelofhemidystoniainducedby3nitropropionicacid
AT liuhuanguang ratmodelofhemidystoniainducedby3nitropropionicacid
AT mayu ratmodelofhemidystoniainducedby3nitropropionicacid
AT mengdawei ratmodelofhemidystoniainducedby3nitropropionicacid
AT yanganchao ratmodelofhemidystoniainducedby3nitropropionicacid
AT zhangjianguo ratmodelofhemidystoniainducedby3nitropropionicacid