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Enhanced histamine H2 excitation of striatal cholinergic interneurons in L-DOPA-induced dyskinesia
Levodopa is the most effective therapy for the motor deficits of Parkinson's disease (PD), but long term treatment leads to the development of L-DOPA-induced dyskinesia (LID). Our previous studies indicate enhanced excitability of striatal cholinergic interneurons (ChIs) in mice expressing LID...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9563247/ https://www.ncbi.nlm.nih.gov/pubmed/25661301 http://dx.doi.org/10.1016/j.nbd.2015.01.003 |
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author | Lim, Sean Austin O. Xia, Rong Ding, Yunmin Won, Lisa Ray, William J. Hitchcock, Stephen A. McGehee, Daniel S. Kang, Un Jung |
author_facet | Lim, Sean Austin O. Xia, Rong Ding, Yunmin Won, Lisa Ray, William J. Hitchcock, Stephen A. McGehee, Daniel S. Kang, Un Jung |
author_sort | Lim, Sean Austin O. |
collection | PubMed |
description | Levodopa is the most effective therapy for the motor deficits of Parkinson's disease (PD), but long term treatment leads to the development of L-DOPA-induced dyskinesia (LID). Our previous studies indicate enhanced excitability of striatal cholinergic interneurons (ChIs) in mice expressing LID and reduction of LID when ChIs are selectively ablated. Recent gene expression analysis indicates that stimulatory H2 histamine receptors are prefentially expressed on ChIs at high levels in the striatum, and we tested whether a change in H2 receptor function might contribute to the elevated excitability in LID. Using two different mouse models of PD (6-hydroxydopamine lesion and Pitx3(ak/ak) mutation), we chronically treated the animals with either vehicle or L-DOPA to induce dyskinesia. Electrophysiological recordings indicate that histamine H2 receptor-mediated excitation of striatal ChIs is enhanced in mice expressing LID. Additionally, H2 receptor blockade by systemic administration of famotidine decreases behavioral LID expression in dyskinetic animals. These findings suggest that ChIs undergo a pathological change in LID with respect to histaminergic neurotransmission. The hypercholinergic striatum associated with LID may be dampened by inhibition of H2 histaminergic neurotransmission. This study also provides a proof of principle of utilizing selective gene expression data for cell-type-specific modulation of neuronal activity. |
format | Online Article Text |
id | pubmed-9563247 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
record_format | MEDLINE/PubMed |
spelling | pubmed-95632472022-10-14 Enhanced histamine H2 excitation of striatal cholinergic interneurons in L-DOPA-induced dyskinesia Lim, Sean Austin O. Xia, Rong Ding, Yunmin Won, Lisa Ray, William J. Hitchcock, Stephen A. McGehee, Daniel S. Kang, Un Jung Neurobiol Dis Article Levodopa is the most effective therapy for the motor deficits of Parkinson's disease (PD), but long term treatment leads to the development of L-DOPA-induced dyskinesia (LID). Our previous studies indicate enhanced excitability of striatal cholinergic interneurons (ChIs) in mice expressing LID and reduction of LID when ChIs are selectively ablated. Recent gene expression analysis indicates that stimulatory H2 histamine receptors are prefentially expressed on ChIs at high levels in the striatum, and we tested whether a change in H2 receptor function might contribute to the elevated excitability in LID. Using two different mouse models of PD (6-hydroxydopamine lesion and Pitx3(ak/ak) mutation), we chronically treated the animals with either vehicle or L-DOPA to induce dyskinesia. Electrophysiological recordings indicate that histamine H2 receptor-mediated excitation of striatal ChIs is enhanced in mice expressing LID. Additionally, H2 receptor blockade by systemic administration of famotidine decreases behavioral LID expression in dyskinetic animals. These findings suggest that ChIs undergo a pathological change in LID with respect to histaminergic neurotransmission. The hypercholinergic striatum associated with LID may be dampened by inhibition of H2 histaminergic neurotransmission. This study also provides a proof of principle of utilizing selective gene expression data for cell-type-specific modulation of neuronal activity. 2015-04 2015-02-04 /pmc/articles/PMC9563247/ /pubmed/25661301 http://dx.doi.org/10.1016/j.nbd.2015.01.003 Text en https://creativecommons.org/licenses/by/4.0/This manuscript version is made available under the CC BY-NC-ND 4.0 license. |
spellingShingle | Article Lim, Sean Austin O. Xia, Rong Ding, Yunmin Won, Lisa Ray, William J. Hitchcock, Stephen A. McGehee, Daniel S. Kang, Un Jung Enhanced histamine H2 excitation of striatal cholinergic interneurons in L-DOPA-induced dyskinesia |
title | Enhanced histamine H2 excitation of striatal cholinergic interneurons in L-DOPA-induced dyskinesia |
title_full | Enhanced histamine H2 excitation of striatal cholinergic interneurons in L-DOPA-induced dyskinesia |
title_fullStr | Enhanced histamine H2 excitation of striatal cholinergic interneurons in L-DOPA-induced dyskinesia |
title_full_unstemmed | Enhanced histamine H2 excitation of striatal cholinergic interneurons in L-DOPA-induced dyskinesia |
title_short | Enhanced histamine H2 excitation of striatal cholinergic interneurons in L-DOPA-induced dyskinesia |
title_sort | enhanced histamine h2 excitation of striatal cholinergic interneurons in l-dopa-induced dyskinesia |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9563247/ https://www.ncbi.nlm.nih.gov/pubmed/25661301 http://dx.doi.org/10.1016/j.nbd.2015.01.003 |
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