Botulinum Neurotoxin A Injected Ipsilaterally or Contralaterally into the Striatum in the Rat 6-OHDA Model of Unilateral Parkinson’s Disease Differently Affects Behavior
Parkinson’s disease (PD) is one of the most frequent neurodegenerative disorders. The loss of dopaminergic neurons in the substantia nigra leads to a disinhibition of cholinergic interneurons in the striatum. Pharmacotherapeutical strategies of PD-related hypercholinism have numerous adverse side ef...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-06-01
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| Series: | Frontiers in Behavioral Neuroscience |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fnbeh.2017.00119/full |
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| author | Veronica A. Antipova Veronica A. Antipova Carsten Holzmann Oliver Schmitt Andreas Wree Alexander Hawlitschka |
| author_facet | Veronica A. Antipova Veronica A. Antipova Carsten Holzmann Oliver Schmitt Andreas Wree Alexander Hawlitschka |
| author_sort | Veronica A. Antipova |
| collection | DOAJ |
| description | Parkinson’s disease (PD) is one of the most frequent neurodegenerative disorders. The loss of dopaminergic neurons in the substantia nigra leads to a disinhibition of cholinergic interneurons in the striatum. Pharmacotherapeutical strategies of PD-related hypercholinism have numerous adverse side effects. We previously showed that ipsilateral intrastriatal injections of 1 ng in unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats inhibit apomorphine-induced rotation behavior significantly up to 6 months. In this study, we extended the behavioral testing of ipsilateral botulinum neurotoxin A (BoNT-A)-injection and additionally investigated the impact of intrastriatal BoNT-A-injections contralateral to the 6-OHDA-lesioned hemisphere on the basal ganglia circuity and motor functions. We hypothesized that the interhemispheric differences of acetylcholine (ACh) concentration seen in unilateral hemi-PD should be differentially and temporally influenced by the ipsilateral or contralateral injection of BoNT-A. Hemi-PD rats were injected with 1 ng BoNT-A or vehicle substance into either the ipsilateral or contralateral striatum 6 weeks after 6-OHDA-lesion and various behaviors were tested. In hemi-PD rats intrastriatal ipsilateral BoNT-A-injections significantly reduced apomorphine-induced rotations and increased amphetamine-induced rotations, but showed no significant improvement of forelimb usage and akinesia, lateralized sensorimotor integration and also no effect on spontaneous locomotor activity. However, intrastriatal BoNT-A-injections contralateral to the lesion led to a significant increase of the apomorphine-induced turning rate only 2 weeks after the treatment. The apomorphine-induced rotation rate decreases thereafter to a value below the initial rotation rate. Amphetamine-induced rotations were not significantly changed after BoNT-A-application in comparison to sham-treated animals. Forelimb usage was temporally improved by contralateral BoNT-A-injection at 2 weeks after BoNT-A. Akinesia and lateralized sensorimotor integration were also improved, but contralateral BoNT-A-injection had no significant effect on spontaneous locomotor activity. These long-ranging and different effects suggest that intrastriatally applied BoNT-A acts not only as an inhibitor of ACh release but also has long-lasting impact on transmitter expression and thereby on the basal ganglia circuitry. Evaluation of changes of transmitter receptors is subject of ongoing studies of our group. |
| first_indexed | 2024-12-11T00:37:43Z |
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| language | English |
| last_indexed | 2024-12-11T00:37:43Z |
| publishDate | 2017-06-01 |
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| spelling | doaj.art-7c0c988a303247a4895a043b917c29d42022-12-22T01:27:03ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532017-06-011110.3389/fnbeh.2017.00119258675Botulinum Neurotoxin A Injected Ipsilaterally or Contralaterally into the Striatum in the Rat 6-OHDA Model of Unilateral Parkinson’s Disease Differently Affects BehaviorVeronica A. Antipova0Veronica A. Antipova1Carsten Holzmann2Oliver Schmitt3Andreas Wree4Alexander Hawlitschka5Institute of Anatomy, Rostock University Medical CenterRostock, GermanyInstitute of Macroscopic and Clinical Anatomy, Medical University of GrazGraz, AustriaInstitute of Medical Genetics, Rostock University Medical CenterRostock, GermanyInstitute of Anatomy, Rostock University Medical CenterRostock, GermanyInstitute of Anatomy, Rostock University Medical CenterRostock, GermanyInstitute of Anatomy, Rostock University Medical CenterRostock, GermanyParkinson’s disease (PD) is one of the most frequent neurodegenerative disorders. The loss of dopaminergic neurons in the substantia nigra leads to a disinhibition of cholinergic interneurons in the striatum. Pharmacotherapeutical strategies of PD-related hypercholinism have numerous adverse side effects. We previously showed that ipsilateral intrastriatal injections of 1 ng in unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats inhibit apomorphine-induced rotation behavior significantly up to 6 months. In this study, we extended the behavioral testing of ipsilateral botulinum neurotoxin A (BoNT-A)-injection and additionally investigated the impact of intrastriatal BoNT-A-injections contralateral to the 6-OHDA-lesioned hemisphere on the basal ganglia circuity and motor functions. We hypothesized that the interhemispheric differences of acetylcholine (ACh) concentration seen in unilateral hemi-PD should be differentially and temporally influenced by the ipsilateral or contralateral injection of BoNT-A. Hemi-PD rats were injected with 1 ng BoNT-A or vehicle substance into either the ipsilateral or contralateral striatum 6 weeks after 6-OHDA-lesion and various behaviors were tested. In hemi-PD rats intrastriatal ipsilateral BoNT-A-injections significantly reduced apomorphine-induced rotations and increased amphetamine-induced rotations, but showed no significant improvement of forelimb usage and akinesia, lateralized sensorimotor integration and also no effect on spontaneous locomotor activity. However, intrastriatal BoNT-A-injections contralateral to the lesion led to a significant increase of the apomorphine-induced turning rate only 2 weeks after the treatment. The apomorphine-induced rotation rate decreases thereafter to a value below the initial rotation rate. Amphetamine-induced rotations were not significantly changed after BoNT-A-application in comparison to sham-treated animals. Forelimb usage was temporally improved by contralateral BoNT-A-injection at 2 weeks after BoNT-A. Akinesia and lateralized sensorimotor integration were also improved, but contralateral BoNT-A-injection had no significant effect on spontaneous locomotor activity. These long-ranging and different effects suggest that intrastriatally applied BoNT-A acts not only as an inhibitor of ACh release but also has long-lasting impact on transmitter expression and thereby on the basal ganglia circuitry. Evaluation of changes of transmitter receptors is subject of ongoing studies of our group.http://journal.frontiersin.org/article/10.3389/fnbeh.2017.00119/fullbotulinum toxinshemiparkinsonismbehaviorWistar ratsstriatum |
| spellingShingle | Veronica A. Antipova Veronica A. Antipova Carsten Holzmann Oliver Schmitt Andreas Wree Alexander Hawlitschka Botulinum Neurotoxin A Injected Ipsilaterally or Contralaterally into the Striatum in the Rat 6-OHDA Model of Unilateral Parkinson’s Disease Differently Affects Behavior Frontiers in Behavioral Neuroscience botulinum toxins hemiparkinsonism behavior Wistar rats striatum |
| title | Botulinum Neurotoxin A Injected Ipsilaterally or Contralaterally into the Striatum in the Rat 6-OHDA Model of Unilateral Parkinson’s Disease Differently Affects Behavior |
| title_full | Botulinum Neurotoxin A Injected Ipsilaterally or Contralaterally into the Striatum in the Rat 6-OHDA Model of Unilateral Parkinson’s Disease Differently Affects Behavior |
| title_fullStr | Botulinum Neurotoxin A Injected Ipsilaterally or Contralaterally into the Striatum in the Rat 6-OHDA Model of Unilateral Parkinson’s Disease Differently Affects Behavior |
| title_full_unstemmed | Botulinum Neurotoxin A Injected Ipsilaterally or Contralaterally into the Striatum in the Rat 6-OHDA Model of Unilateral Parkinson’s Disease Differently Affects Behavior |
| title_short | Botulinum Neurotoxin A Injected Ipsilaterally or Contralaterally into the Striatum in the Rat 6-OHDA Model of Unilateral Parkinson’s Disease Differently Affects Behavior |
| title_sort | botulinum neurotoxin a injected ipsilaterally or contralaterally into the striatum in the rat 6 ohda model of unilateral parkinson s disease differently affects behavior |
| topic | botulinum toxins hemiparkinsonism behavior Wistar rats striatum |
| url | http://journal.frontiersin.org/article/10.3389/fnbeh.2017.00119/full |
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