کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6021372 | 1580632 | 2016 | 49 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Optogenetic activation of striatal cholinergic interneurons regulates L-dopa-induced dyskinesias
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کلمات کلیدی
LIDsAAVnAChRChR2mAChRDATERK6-Hydroxydopamine6-OHDAACh - آهStriatum - استریاتومAcetylcholine - استیل کولینDopamine transporter - انتقال دهنده دوپامینAIMS - اهدافOptogenetics - اپتوژنتیکParkinson's disease - بیماری پارکینسونanalysis of variance - تحلیل واریانسANOVA - تحلیل واریانس Analysis of varianceabnormal involuntary movements - حرکات غیر دائمی غیر طبیعیDyskinesias - دیسکینزیNicotinic - نیکوتینیکAdeno-associated virus - ویروس Adeno مرتبط استChAT - چتcholine acetyltransferase - کولین استیل ترانسفرازmuscarinic acetylcholine receptor - گیرنده استیل کولین muscarinicnicotinic acetylcholine receptor - گیرنده استیلکولین نیکوتین
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
عصب شناسی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Optogenetic activation of striatal cholinergic interneurons regulates L-dopa-induced dyskinesias Optogenetic activation of striatal cholinergic interneurons regulates L-dopa-induced dyskinesias](/preview/png/6021372.png)
چکیده انگلیسی
L-dopa-induced dyskinesias (LIDs) are a serious complication of L-dopa therapy for Parkinson's disease. Emerging evidence indicates that the nicotinic cholinergic system plays a role in LIDs, although the pathways and mechanisms are poorly understood. Here we used optogenetics to investigate the role of striatal cholinergic interneurons in LIDs. Mice expressing cre-recombinase under the control of the choline acetyltransferase promoter (ChAT-Cre) were lesioned by unilateral injection of 6-hydroxydopamine. AAV5-ChR2-eYFP or AAV5-control-eYFP was injected into the dorsolateral striatum, and optical fibers implanted. After stable virus expression, mice were treated with L-dopa. They were then subjected to various stimulation protocols for 2Â h and LIDs rated. Continuous stimulation with a short duration optical pulse (1-5Â ms) enhanced LIDs. This effect was blocked by the general muscarinic acetylcholine receptor (mAChR) antagonist atropine indicating it was mAChR-mediated. By contrast, continuous stimulation with a longer duration optical pulse (20Â ms to 1Â s) reduced LIDs to a similar extent as nicotine treatment (~Â 50%). The general nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine blocked the decline in LIDs with longer optical pulses showing it was nAChR-mediated. None of the stimulation regimens altered LIDs in control-eYFP mice. Lesion-induced motor impairment was not affected by optical stimulation indicating that cholinergic transmission selectively regulates LIDs. Longer pulse stimulation increased the number of c-Fos expressing ChAT neurons, suggesting that changes in this immediate early gene may be involved. These results demonstrate that striatal cholinergic interneurons play a critical role in LIDs and support the idea that nicotine treatment reduces LIDs via nAChR desensitization.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 91, July 2016, Pages 47-58
Journal: Neurobiology of Disease - Volume 91, July 2016, Pages 47-58
نویسندگان
Tanuja Bordia, Xiomara A. Perez, Jaime E. Heiss, Danhui Zhang, Maryka Quik,