当前位置：
X-MOL 学术
›
Neuroscience
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Inhibition of Excessive Glutamatergic Transmission in the Ventral Thalamic Nuclei by a Selective Adenosine A1 Receptor Agonist, 5'-Chloro-5'-Deoxy-(±)-ENBA Underlies its Tremorolytic Effect in the Harmaline-Induced Model of Essential Tremor.
Neuroscience ( IF 2.9 ) Pub Date : 2020-01-11 , DOI: 10.1016/j.neuroscience.2019.12.045 Barbara Kosmowska 1 , Krystyna Ossowska 1 , Jolanta Konieczny 1 , Tomasz Lenda 1 , Klemencja Berghauzen-Maciejewska 1 , Jadwiga Wardas 1
Neuroscience ( IF 2.9 ) Pub Date : 2020-01-11 , DOI: 10.1016/j.neuroscience.2019.12.045 Barbara Kosmowska 1 , Krystyna Ossowska 1 , Jolanta Konieczny 1 , Tomasz Lenda 1 , Klemencja Berghauzen-Maciejewska 1 , Jadwiga Wardas 1
Affiliation
|
The primary cause of harmaline tremor, which is a model of essential tremor (ET) in animals, is excessive activation of olivocerebellar glutamatergic climbing fibers. Our recent study indicated that 5'-chloro-5'-deoxy-(±)-N6-(±)-(endo-norborn-2-yl)adenosine (5'Cl5'd-(±)-ENBA), a potent and selective adenosine A1 receptor (A1) agonist, inhibited harmaline tremor. The present study was aimed to evaluate the role of glutamatergic transmission system in 5'Cl5'd-(±)-ENBA tremorolytic action in the harmaline model in rats, by analyzing glutamate release in the motor nuclei of the thalamus and mRNA expression of glutamatergic neuron markers (vGlut1/2) in reference to the general neuronal activity marker (zif-268) in different brain structures. The extracellular glutamate level in the motor thalamus was evaluated by in vivo microdialysis and the vGlut1/vGlut2 and zif-268 mRNA expression was analyzed by in situ hybridization. The intensity of tremor was measured automatically using Force Plate Actimeters (FPAs). 5'Cl5'd-(±)-ENBA (0.5 mg/kg) given 30 min before harmaline (30 mg/kg) decreased the harmaline-induced excessive glutamate release in the motor thalamus and reversed harmaline-induced molecular effects, such as elevation of the vGlut1 mRNA expression in the inferior olive (IO) and decrease in the motor cortex, as well as an increase of the zif-268 mRNA expression in the IO, motor thalamus and motor cortex. Moreover, 5'Cl5'd-(±)-ENBA reduced harmaline tremor by lowering its power in 9-15 Hz frequency band. Our findings show that A1 stimulation decreases glutamate release in the motor thalamic nuclei in the harmaline model of ET, suggesting that A1 receptors, especially in this structure, may be a potential therapeutic target in this disorder.
中文翻译：
选择性腺苷A1受体激动剂5'-Chloro-5'-Deoxy-（±）-ENBA抑制丘脑丘脑核中的过量谷氨酸能传递是其在原发性震颤诱导的模型中的溶瘤作用的基础。
harmaline震颤（动物固有震颤（ET）的模型）的主要原因是小脑谷氨酸谷氨酸能爬升纤维过度活化。我们最近的研究表明5'-chloro-5'-deoxy-（±）-N6-（±）-（endo-norborn-2-yl）腺苷（5'Cl5'd-（±）-ENBA）强效和选择性的腺苷A1受体（A1）激动剂，抑制harmaline震颤。本研究旨在通过分析丘脑运动核中谷氨酸的释放以及谷氨酸能的mRNA表达来评估谷氨酸能传递系统在大鼠harmaline模型中的5'Cl5'd-（±）-ENBA溶血作用中的作用。神经元标记（vGlut1 / 2），指不同大脑结构中的一般神经元活动标记（zif-268）。通过体内微透析评估运动丘脑中的细胞外谷氨酸水平，并通过原位杂交分析vGlut1 / vGlut2和zif-268 mRNA的表达。震颤强度是使用测力板测厚仪（FPA）自动测量的。在harmaline（30 mg / kg）之前30分钟给予5'Cl5'd-（±）-ENBA（0.5 mg / kg）可以减少harmaline引起的运动丘脑中过量谷氨酸的释放并逆转harmaline引起的分子效应，例如下橄榄（IO）中vGlut1 mRNA表达的升高，运动皮层中的表达降低，以及IO，丘脑和运动皮层中zif-268 mRNA的表达增加。此外，5'Cl5'd-（±）-ENBA通过降低9-15 Hz频带的功率来降低harmaline震颤。
更新日期：2020-01-13
中文翻译：
选择性腺苷A1受体激动剂5'-Chloro-5'-Deoxy-（±）-ENBA抑制丘脑丘脑核中的过量谷氨酸能传递是其在原发性震颤诱导的模型中的溶瘤作用的基础。
harmaline震颤（动物固有震颤（ET）的模型）的主要原因是小脑谷氨酸谷氨酸能爬升纤维过度活化。我们最近的研究表明5'-chloro-5'-deoxy-（±）-N6-（±）-（endo-norborn-2-yl）腺苷（5'Cl5'd-（±）-ENBA）强效和选择性的腺苷A1受体（A1）激动剂，抑制harmaline震颤。本研究旨在通过分析丘脑运动核中谷氨酸的释放以及谷氨酸能的mRNA表达来评估谷氨酸能传递系统在大鼠harmaline模型中的5'Cl5'd-（±）-ENBA溶血作用中的作用。神经元标记（vGlut1 / 2），指不同大脑结构中的一般神经元活动标记（zif-268）。通过体内微透析评估运动丘脑中的细胞外谷氨酸水平，并通过原位杂交分析vGlut1 / vGlut2和zif-268 mRNA的表达。震颤强度是使用测力板测厚仪（FPA）自动测量的。在harmaline（30 mg / kg）之前30分钟给予5'Cl5'd-（±）-ENBA（0.5 mg / kg）可以减少harmaline引起的运动丘脑中过量谷氨酸的释放并逆转harmaline引起的分子效应，例如下橄榄（IO）中vGlut1 mRNA表达的升高，运动皮层中的表达降低，以及IO，丘脑和运动皮层中zif-268 mRNA的表达增加。此外，5'Cl5'd-（±）-ENBA通过降低9-15 Hz频带的功率来降低harmaline震颤。
京公网安备 11010802027423号