High frequency stimulation of the subthalamic nucleus improves speed of locomotion but impairs forelimb movement in Parkinsonian rats
Abstract The subthalamic nucleus (STN) plays an important role in motor and non-motor behavior in Parkinson’s disease, but its involvement in gait functions is largely unknown. In this study, we investigated the role of the STN on gait in a rat model of PD using the CatWalk method. Parkinsonian rats...
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| Veröffentlicht in: | Neuroscience 2007-09, Vol.148 (3), p.815-823 |
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| creator | Vlamings, R Visser-Vandewalle, V Koopmans, G Joosten, E.A.J Kozan, R Kaplan, S Steinbusch, H.W.M Temel, Y |
| description | Abstract The subthalamic nucleus (STN) plays an important role in motor and non-motor behavior in Parkinson’s disease, but its involvement in gait functions is largely unknown. In this study, we investigated the role of the STN on gait in a rat model of PD using the CatWalk method. Parkinsonian rats received bilateral high frequency stimulation (HFS) with different stimulation amplitudes of the STN. Rats were rendered parkinsonian by bilateral injections of 6-hydroxydopamine (6-OHDA) into the striatum. One group of 6-OHDA animals was implanted bilaterally with stimulation electrodes at the level of the STN. Stimulations were performed at 130 Hz (frequency), 60 μs (pulse width) and varying amplitudes of 0, 3, 30 and 150 μA. Rats were evaluated in an automated quantitative gait analysis method (CatWalk method). After behavioral evaluations, rats were killed and the brains processed for histological stainings to determine the impact of the dopaminergic lesion (tyrosine hydroxylase immunohistochemistry) and the localization of the electrode tip (hematoxylin–eosin histochemistry). Results show that bilateral 6-OHDA infusion significantly decreased (70%) the number of dopaminergic cells in the substantia nigra pars compacta (SNc). Due to 6-OHDA treatment, the gait parameters changed considerably. There was a general slowness. The most pronounced effects were seen at the level of the hind paws. Due to implantation of STN electrodes the step pattern changed. STN electrical stimulation improved the general slowness but induced slowing of the forelimb movement. Furthermore, we found that HFS with a medium amplitude significantly changed speed, the so-called dynamic aspect of gait. The static features of gait were only significantly influenced with low amplitude. Remarkably, STN stimulation affected predominantly the forepaws/limbs. |
| doi_str_mv | 10.1016/j.neuroscience.2007.06.043 |
| format | Article |
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In this study, we investigated the role of the STN on gait in a rat model of PD using the CatWalk method. Parkinsonian rats received bilateral high frequency stimulation (HFS) with different stimulation amplitudes of the STN. Rats were rendered parkinsonian by bilateral injections of 6-hydroxydopamine (6-OHDA) into the striatum. One group of 6-OHDA animals was implanted bilaterally with stimulation electrodes at the level of the STN. Stimulations were performed at 130 Hz (frequency), 60 μs (pulse width) and varying amplitudes of 0, 3, 30 and 150 μA. Rats were evaluated in an automated quantitative gait analysis method (CatWalk method). After behavioral evaluations, rats were killed and the brains processed for histological stainings to determine the impact of the dopaminergic lesion (tyrosine hydroxylase immunohistochemistry) and the localization of the electrode tip (hematoxylin–eosin histochemistry). Results show that bilateral 6-OHDA infusion significantly decreased (70%) the number of dopaminergic cells in the substantia nigra pars compacta (SNc). Due to 6-OHDA treatment, the gait parameters changed considerably. There was a general slowness. The most pronounced effects were seen at the level of the hind paws. Due to implantation of STN electrodes the step pattern changed. STN electrical stimulation improved the general slowness but induced slowing of the forelimb movement. Furthermore, we found that HFS with a medium amplitude significantly changed speed, the so-called dynamic aspect of gait. The static features of gait were only significantly influenced with low amplitude. Remarkably, STN stimulation affected predominantly the forepaws/limbs.</description><identifier>ISSN: 0306-4522</identifier><identifier>EISSN: 1873-7544</identifier><identifier>DOI: 10.1016/j.neuroscience.2007.06.043</identifier><identifier>PMID: 17706885</identifier><identifier>CODEN: NRSCDN</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>6-OHDA ; Animals ; Biological and medical sciences ; CatWalk ; Corpus Striatum - drug effects ; Corpus Striatum - physiopathology ; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases ; Denervation ; Disease Models, Animal ; Dopamine - metabolism ; Electric Stimulation Therapy - adverse effects ; Electric Stimulation Therapy - instrumentation ; Electric Stimulation Therapy - methods ; Electrodes, Implanted - adverse effects ; Forelimb - innervation ; Forelimb - physiopathology ; Fundamental and applied biological sciences. Psychology ; gait ; Gait - physiology ; Gait Disorders, Neurologic - physiopathology ; Gait Disorders, Neurologic - therapy ; high frequency stimulation ; Locomotion - physiology ; Male ; Medical sciences ; Nerve Degeneration - chemically induced ; Nerve Degeneration - metabolism ; Nerve Degeneration - physiopathology ; Neurology ; Neurotoxins ; Oxidopamine ; Parkinsonian Disorders - physiopathology ; Parkinsonian Disorders - therapy ; Parkinson’s disease ; Rats ; Rats, Inbred Lew ; Substantia Nigra - metabolism ; Substantia Nigra - pathology ; Substantia Nigra - physiopathology ; subthalamic nucleus ; Subthalamic Nucleus - physiopathology ; Treatment Outcome ; Tyrosine 3-Monooxygenase - metabolism ; Vertebrates: nervous system and sense organs</subject><ispartof>Neuroscience, 2007-09, Vol.148 (3), p.815-823</ispartof><rights>IBRO</rights><rights>2007 IBRO</rights><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c475t-c9d68f50349de2b1fd8181e88f243df330b6c176c2d8c187431b278a0ce9dc0f3</citedby><cites>FETCH-LOGICAL-c475t-c9d68f50349de2b1fd8181e88f243df330b6c176c2d8c187431b278a0ce9dc0f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0306452207008032$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19143130$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17706885$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vlamings, R</creatorcontrib><creatorcontrib>Visser-Vandewalle, V</creatorcontrib><creatorcontrib>Koopmans, G</creatorcontrib><creatorcontrib>Joosten, E.A.J</creatorcontrib><creatorcontrib>Kozan, R</creatorcontrib><creatorcontrib>Kaplan, S</creatorcontrib><creatorcontrib>Steinbusch, H.W.M</creatorcontrib><creatorcontrib>Temel, Y</creatorcontrib><title>High frequency stimulation of the subthalamic nucleus improves speed of locomotion but impairs forelimb movement in Parkinsonian rats</title><title>Neuroscience</title><addtitle>Neuroscience</addtitle><description>Abstract The subthalamic nucleus (STN) plays an important role in motor and non-motor behavior in Parkinson’s disease, but its involvement in gait functions is largely unknown. In this study, we investigated the role of the STN on gait in a rat model of PD using the CatWalk method. Parkinsonian rats received bilateral high frequency stimulation (HFS) with different stimulation amplitudes of the STN. Rats were rendered parkinsonian by bilateral injections of 6-hydroxydopamine (6-OHDA) into the striatum. One group of 6-OHDA animals was implanted bilaterally with stimulation electrodes at the level of the STN. Stimulations were performed at 130 Hz (frequency), 60 μs (pulse width) and varying amplitudes of 0, 3, 30 and 150 μA. Rats were evaluated in an automated quantitative gait analysis method (CatWalk method). After behavioral evaluations, rats were killed and the brains processed for histological stainings to determine the impact of the dopaminergic lesion (tyrosine hydroxylase immunohistochemistry) and the localization of the electrode tip (hematoxylin–eosin histochemistry). Results show that bilateral 6-OHDA infusion significantly decreased (70%) the number of dopaminergic cells in the substantia nigra pars compacta (SNc). Due to 6-OHDA treatment, the gait parameters changed considerably. There was a general slowness. The most pronounced effects were seen at the level of the hind paws. Due to implantation of STN electrodes the step pattern changed. STN electrical stimulation improved the general slowness but induced slowing of the forelimb movement. Furthermore, we found that HFS with a medium amplitude significantly changed speed, the so-called dynamic aspect of gait. The static features of gait were only significantly influenced with low amplitude. Remarkably, STN stimulation affected predominantly the forepaws/limbs.</description><subject>6-OHDA</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>CatWalk</subject><subject>Corpus Striatum - drug effects</subject><subject>Corpus Striatum - physiopathology</subject><subject>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</subject><subject>Denervation</subject><subject>Disease Models, Animal</subject><subject>Dopamine - metabolism</subject><subject>Electric Stimulation Therapy - adverse effects</subject><subject>Electric Stimulation Therapy - instrumentation</subject><subject>Electric Stimulation Therapy - methods</subject><subject>Electrodes, Implanted - adverse effects</subject><subject>Forelimb - innervation</subject><subject>Forelimb - physiopathology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>gait</subject><subject>Gait - physiology</subject><subject>Gait Disorders, Neurologic - physiopathology</subject><subject>Gait Disorders, Neurologic - therapy</subject><subject>high frequency stimulation</subject><subject>Locomotion - physiology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Nerve Degeneration - chemically induced</subject><subject>Nerve Degeneration - metabolism</subject><subject>Nerve Degeneration - physiopathology</subject><subject>Neurology</subject><subject>Neurotoxins</subject><subject>Oxidopamine</subject><subject>Parkinsonian Disorders - physiopathology</subject><subject>Parkinsonian Disorders - therapy</subject><subject>Parkinson’s disease</subject><subject>Rats</subject><subject>Rats, Inbred Lew</subject><subject>Substantia Nigra - metabolism</subject><subject>Substantia Nigra - pathology</subject><subject>Substantia Nigra - physiopathology</subject><subject>subthalamic nucleus</subject><subject>Subthalamic Nucleus - physiopathology</subject><subject>Treatment Outcome</subject><subject>Tyrosine 3-Monooxygenase - metabolism</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0306-4522</issn><issn>1873-7544</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNks9u1DAQxiMEotvCKyALCW4JYzt_vByQqkIpUiWQgLPlOGPW28Re7LjSPgDvjcNGKuKELz74NzOfv2-K4iWFigJt3-wrhyn4qC06jRUD6CpoK6j5o2JDRcfLrqnrx8UGOLRl3TB2VpzHuId8mpo_Lc5o10ErRLMpft3YHztiAv5MudmRxNlOaVSz9Y54Q-Ydkpj6eadGNVlNXNIjpkjsdAj-HiOJB8RhIUev_eT_1PVpXgBlQyTGBxzt1JMp4xO6_OLIFxXurIveWeVIUHN8Vjwxaoz4fL0viu_XH75d3ZS3nz9-urq8LXXdNXOpt0MrTAO83g7IemoGQQVFIQyr-WA4h77VtGs1G4TORtSc9qwTCjRuBw2GXxSvT32z-vzhOMvJRo3jqBz6FCUDzlnLWAbfnkCdfY4BjTwEO6lwlBTkEoLcy79DkEsIElqZQ8jFL9YpqZ9weChdXc_AqxVQUavRBOW0jQ_clmblHDL3_sRh9uTeYpDruMEG1LMcvP0_Pe_-aaNH62yefIdHjHufgsuuSyojkyC_LmuzbA10AAI4478BwabE3Q</recordid><startdate>20070907</startdate><enddate>20070907</enddate><creator>Vlamings, R</creator><creator>Visser-Vandewalle, V</creator><creator>Koopmans, G</creator><creator>Joosten, E.A.J</creator><creator>Kozan, R</creator><creator>Kaplan, S</creator><creator>Steinbusch, H.W.M</creator><creator>Temel, Y</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7TK</scope></search><sort><creationdate>20070907</creationdate><title>High frequency stimulation of the subthalamic nucleus improves speed of locomotion but impairs forelimb movement in Parkinsonian rats</title><author>Vlamings, R ; Visser-Vandewalle, V ; Koopmans, G ; Joosten, E.A.J ; Kozan, R ; Kaplan, S ; Steinbusch, H.W.M ; Temel, Y</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c475t-c9d68f50349de2b1fd8181e88f243df330b6c176c2d8c187431b278a0ce9dc0f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>6-OHDA</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>CatWalk</topic><topic>Corpus Striatum - drug effects</topic><topic>Corpus Striatum - physiopathology</topic><topic>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</topic><topic>Denervation</topic><topic>Disease Models, Animal</topic><topic>Dopamine - metabolism</topic><topic>Electric Stimulation Therapy - adverse effects</topic><topic>Electric Stimulation Therapy - instrumentation</topic><topic>Electric Stimulation Therapy - methods</topic><topic>Electrodes, Implanted - adverse effects</topic><topic>Forelimb - innervation</topic><topic>Forelimb - physiopathology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>gait</topic><topic>Gait - physiology</topic><topic>Gait Disorders, Neurologic - physiopathology</topic><topic>Gait Disorders, Neurologic - therapy</topic><topic>high frequency stimulation</topic><topic>Locomotion - physiology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Nerve Degeneration - chemically induced</topic><topic>Nerve Degeneration - metabolism</topic><topic>Nerve Degeneration - physiopathology</topic><topic>Neurology</topic><topic>Neurotoxins</topic><topic>Oxidopamine</topic><topic>Parkinsonian Disorders - physiopathology</topic><topic>Parkinsonian Disorders - therapy</topic><topic>Parkinson’s disease</topic><topic>Rats</topic><topic>Rats, Inbred Lew</topic><topic>Substantia Nigra - metabolism</topic><topic>Substantia Nigra - pathology</topic><topic>Substantia Nigra - physiopathology</topic><topic>subthalamic nucleus</topic><topic>Subthalamic Nucleus - physiopathology</topic><topic>Treatment Outcome</topic><topic>Tyrosine 3-Monooxygenase - metabolism</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vlamings, R</creatorcontrib><creatorcontrib>Visser-Vandewalle, V</creatorcontrib><creatorcontrib>Koopmans, G</creatorcontrib><creatorcontrib>Joosten, E.A.J</creatorcontrib><creatorcontrib>Kozan, R</creatorcontrib><creatorcontrib>Kaplan, S</creatorcontrib><creatorcontrib>Steinbusch, H.W.M</creatorcontrib><creatorcontrib>Temel, Y</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Neurosciences Abstracts</collection><jtitle>Neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vlamings, R</au><au>Visser-Vandewalle, V</au><au>Koopmans, G</au><au>Joosten, E.A.J</au><au>Kozan, R</au><au>Kaplan, S</au><au>Steinbusch, H.W.M</au><au>Temel, Y</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High frequency stimulation of the subthalamic nucleus improves speed of locomotion but impairs forelimb movement in Parkinsonian rats</atitle><jtitle>Neuroscience</jtitle><addtitle>Neuroscience</addtitle><date>2007-09-07</date><risdate>2007</risdate><volume>148</volume><issue>3</issue><spage>815</spage><epage>823</epage><pages>815-823</pages><issn>0306-4522</issn><eissn>1873-7544</eissn><coden>NRSCDN</coden><abstract>Abstract The subthalamic nucleus (STN) plays an important role in motor and non-motor behavior in Parkinson’s disease, but its involvement in gait functions is largely unknown. In this study, we investigated the role of the STN on gait in a rat model of PD using the CatWalk method. Parkinsonian rats received bilateral high frequency stimulation (HFS) with different stimulation amplitudes of the STN. Rats were rendered parkinsonian by bilateral injections of 6-hydroxydopamine (6-OHDA) into the striatum. One group of 6-OHDA animals was implanted bilaterally with stimulation electrodes at the level of the STN. Stimulations were performed at 130 Hz (frequency), 60 μs (pulse width) and varying amplitudes of 0, 3, 30 and 150 μA. Rats were evaluated in an automated quantitative gait analysis method (CatWalk method). After behavioral evaluations, rats were killed and the brains processed for histological stainings to determine the impact of the dopaminergic lesion (tyrosine hydroxylase immunohistochemistry) and the localization of the electrode tip (hematoxylin–eosin histochemistry). Results show that bilateral 6-OHDA infusion significantly decreased (70%) the number of dopaminergic cells in the substantia nigra pars compacta (SNc). Due to 6-OHDA treatment, the gait parameters changed considerably. There was a general slowness. The most pronounced effects were seen at the level of the hind paws. Due to implantation of STN electrodes the step pattern changed. STN electrical stimulation improved the general slowness but induced slowing of the forelimb movement. Furthermore, we found that HFS with a medium amplitude significantly changed speed, the so-called dynamic aspect of gait. The static features of gait were only significantly influenced with low amplitude. Remarkably, STN stimulation affected predominantly the forepaws/limbs.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>17706885</pmid><doi>10.1016/j.neuroscience.2007.06.043</doi><tpages>9</tpages></addata></record> |
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| subjects | 6-OHDA Animals Biological and medical sciences CatWalk Corpus Striatum - drug effects Corpus Striatum - physiopathology Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Denervation Disease Models, Animal Dopamine - metabolism Electric Stimulation Therapy - adverse effects Electric Stimulation Therapy - instrumentation Electric Stimulation Therapy - methods Electrodes, Implanted - adverse effects Forelimb - innervation Forelimb - physiopathology Fundamental and applied biological sciences. Psychology gait Gait - physiology Gait Disorders, Neurologic - physiopathology Gait Disorders, Neurologic - therapy high frequency stimulation Locomotion - physiology Male Medical sciences Nerve Degeneration - chemically induced Nerve Degeneration - metabolism Nerve Degeneration - physiopathology Neurology Neurotoxins Oxidopamine Parkinsonian Disorders - physiopathology Parkinsonian Disorders - therapy Parkinson’s disease Rats Rats, Inbred Lew Substantia Nigra - metabolism Substantia Nigra - pathology Substantia Nigra - physiopathology subthalamic nucleus Subthalamic Nucleus - physiopathology Treatment Outcome Tyrosine 3-Monooxygenase - metabolism Vertebrates: nervous system and sense organs |
| title | High frequency stimulation of the subthalamic nucleus improves speed of locomotion but impairs forelimb movement in Parkinsonian rats |
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