Esther Kim , Imane Frouni , Judy Shaqfah , Dominique Bédard , Philippe Huot
{"title":"半帕金森大鼠大脑中代谢型谷氨酸 2/3 型受体的自动放射标记","authors":"Esther Kim , Imane Frouni , Judy Shaqfah , Dominique Bédard , Philippe Huot","doi":"10.1016/j.jchemneu.2024.102422","DOIUrl":null,"url":null,"abstract":"<div><p>L-3,4-dihydroxyphenylalanine (L-DOPA) is the treatment of choice for Parkinson’s disease (PD) motor symptoms, but its chronic use is hindered by complications such as dyskinesia. Pre-clinical studies discovered that activation of metabotropic glutamate type 2 and 3 (mGlu<sub>2/3</sub>) receptors alleviates L-DOPA-induced dyskinesia. To gain mechanistic insight into the anti-dyskinetic activity of mGlu<sub>2/3</sub> activation, we performed autoradiographic binding with [<sup>3</sup>H]-LY-341,495 in brain sections from L-DOPA-treated 6-hydroxydopamine (6-OHDA)-lesioned rats that developed mild or severe dyskinesia, as well as L-DOPA-untreated 6-OHDA-lesioned and sham-lesioned animals. In the ipsilateral hemisphere, mildly dyskinetic 6-OHDA-lesioned rats showed a decrease in [<sup>3</sup>H]-LY-341,495 binding in the entopeduncular nucleus (EPN, 30 % vs sham-lesioned rats, <em>P</em><0.05), globus pallidus (GP, 28 % vs sham-lesioned rats, <em>P</em><0.05; 23 % vs L-DOPA-untreated 6-OHDA-lesioned rats, <em>P</em><0.001), and primary motor cortex (49 % vs sham-lesioned rats, <em>P</em><0.05; 45 % vs L-DOPA-untreated 6-OHDA-lesioned rats, <em>P</em><0.001). Severely dyskinetic 6-OHDA-lesioned rats exhibited an increase in binding in the primary motor cortex (43 % vs mildly dyskinetic 6-OHDA-lesioned rats, <em>P</em><0.05). In the contralateral hemisphere, mildly dyskinetic 6-OHDA-lesioned rats harboured a decrease in binding in the EPN (30 % vs sham-lesioned rats; 24 % vs L-DOPA-untreated 6-OHDA-lesioned rats, both <em>P</em><0.05), GP (34 % vs sham-lesioned rats, <em>P</em><0.05; 23 % vs L-DOPA-untreated 6-OHDA-lesioned rats, <em>P</em><0.001), and primary motor cortex (50 % vs sham-lesioned rats; 44 % vs L-DOPA-untreated 6-OHDA-lesioned rats, both <em>P</em><0.05). Severely dyskinetic 6-OHDA-lesioned rats presented a decrease in binding in the GP (30 % vs sham-lesioned rats; 19 % vs L-DOPA-untreated 6-OHDA-lesioned rats, both <em>P</em><0.05). Abnormal involuntary movements scores of 6-OHDA-lesioned animals were positively correlated with [<sup>3</sup>H]-LY-341,495 binding in the ipsilateral striatum, ipsilateral EPN, ipsilateral primary motor cortex and contralateral primary motor cortex (all <em>P</em><0.05). These results suggest that alterations in mGlu<sub>2/3</sub> receptor levels may be part of an endogenous compensatory mechanism to alleviate dyskinesia.</p></div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":null,"pages":null},"PeriodicalIF":2.7000,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0891061824000358/pdfft?md5=ec2ef69433d73816b2c7b2d6f385eb7d&pid=1-s2.0-S0891061824000358-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Autoradiographic labelling of metabotropic glutamate type 2/3 receptors in the hemi-parkinsonian rat brain\",\"authors\":\"Esther Kim , Imane Frouni , Judy Shaqfah , Dominique Bédard , Philippe Huot\",\"doi\":\"10.1016/j.jchemneu.2024.102422\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>L-3,4-dihydroxyphenylalanine (L-DOPA) is the treatment of choice for Parkinson’s disease (PD) motor symptoms, but its chronic use is hindered by complications such as dyskinesia. Pre-clinical studies discovered that activation of metabotropic glutamate type 2 and 3 (mGlu<sub>2/3</sub>) receptors alleviates L-DOPA-induced dyskinesia. To gain mechanistic insight into the anti-dyskinetic activity of mGlu<sub>2/3</sub> activation, we performed autoradiographic binding with [<sup>3</sup>H]-LY-341,495 in brain sections from L-DOPA-treated 6-hydroxydopamine (6-OHDA)-lesioned rats that developed mild or severe dyskinesia, as well as L-DOPA-untreated 6-OHDA-lesioned and sham-lesioned animals. In the ipsilateral hemisphere, mildly dyskinetic 6-OHDA-lesioned rats showed a decrease in [<sup>3</sup>H]-LY-341,495 binding in the entopeduncular nucleus (EPN, 30 % vs sham-lesioned rats, <em>P</em><0.05), globus pallidus (GP, 28 % vs sham-lesioned rats, <em>P</em><0.05; 23 % vs L-DOPA-untreated 6-OHDA-lesioned rats, <em>P</em><0.001), and primary motor cortex (49 % vs sham-lesioned rats, <em>P</em><0.05; 45 % vs L-DOPA-untreated 6-OHDA-lesioned rats, <em>P</em><0.001). Severely dyskinetic 6-OHDA-lesioned rats exhibited an increase in binding in the primary motor cortex (43 % vs mildly dyskinetic 6-OHDA-lesioned rats, <em>P</em><0.05). In the contralateral hemisphere, mildly dyskinetic 6-OHDA-lesioned rats harboured a decrease in binding in the EPN (30 % vs sham-lesioned rats; 24 % vs L-DOPA-untreated 6-OHDA-lesioned rats, both <em>P</em><0.05), GP (34 % vs sham-lesioned rats, <em>P</em><0.05; 23 % vs L-DOPA-untreated 6-OHDA-lesioned rats, <em>P</em><0.001), and primary motor cortex (50 % vs sham-lesioned rats; 44 % vs L-DOPA-untreated 6-OHDA-lesioned rats, both <em>P</em><0.05). Severely dyskinetic 6-OHDA-lesioned rats presented a decrease in binding in the GP (30 % vs sham-lesioned rats; 19 % vs L-DOPA-untreated 6-OHDA-lesioned rats, both <em>P</em><0.05). Abnormal involuntary movements scores of 6-OHDA-lesioned animals were positively correlated with [<sup>3</sup>H]-LY-341,495 binding in the ipsilateral striatum, ipsilateral EPN, ipsilateral primary motor cortex and contralateral primary motor cortex (all <em>P</em><0.05). These results suggest that alterations in mGlu<sub>2/3</sub> receptor levels may be part of an endogenous compensatory mechanism to alleviate dyskinesia.</p></div>\",\"PeriodicalId\":15324,\"journal\":{\"name\":\"Journal of chemical neuroanatomy\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2024-04-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0891061824000358/pdfft?md5=ec2ef69433d73816b2c7b2d6f385eb7d&pid=1-s2.0-S0891061824000358-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of chemical neuroanatomy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0891061824000358\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of chemical neuroanatomy","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0891061824000358","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
L-3,4-二羟基苯丙氨酸（L-DOPA）是治疗帕金森病（PD）运动症状的首选药物，但其长期使用受到运动障碍等并发症的阻碍。临床前研究发现，激活代谢型谷氨酸 2 型和 3 型（mGlu2/3）受体可减轻 L-DOPA 引起的运动障碍。为了深入了解激活 mGlu2/3 受体抗运动障碍的机理，我们在经 L-DOPA 治疗的 6-羟基多巴胺（6-OHDA）缺失大鼠出现轻度或重度运动障碍的脑切片中，以及未经 L-DOPA 治疗的 6-OHDA 缺失动物和假缺失动物的脑切片中，用[3H]-LY-341,495 进行了自显影结合。在同侧大脑半球，轻度运动障碍的 6-OHDA 失神经节大鼠显示，在内侧脑核（EPN，30% vs 假失神经节大鼠，P<0.05）、苍白球（GP，28% vs 假失神经节大鼠，P<0.05; 23 % vs L-DOPA-untreated 6-OHDA-lesioned rats, P<0.001）和初级运动皮层（49 % vs 假缺损大鼠，P<0.05; 45 % vs L-DOPA-untreated 6-OHDA-lesioned rats, P<0.001）。严重运动障碍的 6-OHDA 失神经节大鼠表现出初级运动皮层结合力增加（43% vs 轻度运动障碍的 6-OHDA 失神经节大鼠，P<0.05）。在对侧半球，轻度运动障碍的 6-OHDA 病变大鼠在 EPN（30 % vs 假缺损大鼠；24 % vs L-DOPA 未处理的 6-OHDA 病变大鼠，均为 P<0.05）、GP（34 % vs L-DOPA 未处理的 6-OHDA 病变大鼠，均为 P<0.0505）、GP（34 % vs 假缺失大鼠，P<0.05；23 % vs L-DOPA-untreated 6-OHDA-lesioned 大鼠，P<0.001）和初级运动皮层（50 % vs 假缺失大鼠；44 % vs L-DOPA-untreated 6-OHDA-lesioned 大鼠，均为 P<0.05）。严重运动障碍的 6-OHDA 病变大鼠 GP 结合力下降（30% vs 假缺失大鼠；19% vs L-DOPA 未治疗的 6-OHDA 病变大鼠，均为 P<0.05）。6-OHDA缺失动物的异常不自主运动评分与同侧纹状体、同侧EPN、同侧初级运动皮层和对侧初级运动皮层中的[3H]-LY-341,495结合呈正相关（均为P<0.05）。这些结果表明，mGlu2/3 受体水平的改变可能是缓解运动障碍的内源性代偿机制的一部分。
Autoradiographic labelling of metabotropic glutamate type 2/3 receptors in the hemi-parkinsonian rat brain
L-3,4-dihydroxyphenylalanine (L-DOPA) is the treatment of choice for Parkinson’s disease (PD) motor symptoms, but its chronic use is hindered by complications such as dyskinesia. Pre-clinical studies discovered that activation of metabotropic glutamate type 2 and 3 (mGlu2/3) receptors alleviates L-DOPA-induced dyskinesia. To gain mechanistic insight into the anti-dyskinetic activity of mGlu2/3 activation, we performed autoradiographic binding with [3H]-LY-341,495 in brain sections from L-DOPA-treated 6-hydroxydopamine (6-OHDA)-lesioned rats that developed mild or severe dyskinesia, as well as L-DOPA-untreated 6-OHDA-lesioned and sham-lesioned animals. In the ipsilateral hemisphere, mildly dyskinetic 6-OHDA-lesioned rats showed a decrease in [3H]-LY-341,495 binding in the entopeduncular nucleus (EPN, 30 % vs sham-lesioned rats, P<0.05), globus pallidus (GP, 28 % vs sham-lesioned rats, P<0.05; 23 % vs L-DOPA-untreated 6-OHDA-lesioned rats, P<0.001), and primary motor cortex (49 % vs sham-lesioned rats, P<0.05; 45 % vs L-DOPA-untreated 6-OHDA-lesioned rats, P<0.001). Severely dyskinetic 6-OHDA-lesioned rats exhibited an increase in binding in the primary motor cortex (43 % vs mildly dyskinetic 6-OHDA-lesioned rats, P<0.05). In the contralateral hemisphere, mildly dyskinetic 6-OHDA-lesioned rats harboured a decrease in binding in the EPN (30 % vs sham-lesioned rats; 24 % vs L-DOPA-untreated 6-OHDA-lesioned rats, both P<0.05), GP (34 % vs sham-lesioned rats, P<0.05; 23 % vs L-DOPA-untreated 6-OHDA-lesioned rats, P<0.001), and primary motor cortex (50 % vs sham-lesioned rats; 44 % vs L-DOPA-untreated 6-OHDA-lesioned rats, both P<0.05). Severely dyskinetic 6-OHDA-lesioned rats presented a decrease in binding in the GP (30 % vs sham-lesioned rats; 19 % vs L-DOPA-untreated 6-OHDA-lesioned rats, both P<0.05). Abnormal involuntary movements scores of 6-OHDA-lesioned animals were positively correlated with [3H]-LY-341,495 binding in the ipsilateral striatum, ipsilateral EPN, ipsilateral primary motor cortex and contralateral primary motor cortex (all P<0.05). These results suggest that alterations in mGlu2/3 receptor levels may be part of an endogenous compensatory mechanism to alleviate dyskinesia.
期刊介绍：
The Journal of Chemical Neuroanatomy publishes scientific reports relating the functional and biochemical aspects of the nervous system with its microanatomical organization. The scope of the journal concentrates on reports which combine microanatomical, biochemical, pharmacological and behavioural approaches.
Papers should offer original data correlating the morphology of the nervous system (the brain and spinal cord in particular) with its biochemistry. The Journal of Chemical Neuroanatomy is particularly interested in publishing important studies performed with up-to-date methodology utilizing sensitive chemical microassays, hybridoma technology, immunocytochemistry, in situ hybridization and receptor radioautography, to name a few examples.
The Journal of Chemical Neuroanatomy is the natural vehicle for integrated studies utilizing these approaches. The articles will be selected by the editorial board and invited reviewers on the basis of their excellence and potential contribution to this field of neurosciences. Both in vivo and in vitro integrated studies in chemical neuroanatomy are appropriate subjects of interest to the journal. These studies should relate only to vertebrate species with particular emphasis on the mammalian and primate nervous systems.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
