The rat rotenone model reproduces the abnormal pattern of central catecholamine metabolism found in Parkinson's disease.
The rat rotenone model reproduces the abnormal pattern of central catecholamine metabolism found in Parkinson's disease.
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DOI：
10.1242/dmm.049082
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发表时间：
2022-01-01
影响因子：
4.3
通讯作者：
Sharabi Y
中科院分区：
文献类型：
--
作者：
Landau R;Halperin R;Sullivan P;Zibly Z;Leibowitz A;Goldstein DS;Sharabi Y
最近的报告表明，帕金森病（PD）涉及特定的功能异常，在残留的神经元-减少囊泡隔离细胞质儿茶酚胺通过囊泡单胺转运蛋白（VMAT）和减少醛脱氢酶（ALDH）的活动。这种双重打击建立了自毒代谢产物3，4-二羟基苯乙醛（DOPAL），这是PD发病机制的儿茶酚醛假说的焦点。需要一种动物模型来复制这种异常的儿茶酚胺神经化学模式。成年大鼠接受皮下媒介物或线粒体复合物1抑制剂鱼藤酮（2 mg/kg/天，通过微型泵），持续10天。 记录自发活动，并对纹状体组织进行采样，以测定表明上述异常的儿茶酚含量和儿茶酚比率。与溶剂相比，鱼藤酮降低了自发活动（P=0.002），降低了组织多巴胺浓度（P=0.00001），降低了囊泡隔离指数（3，4-二羟基苯乙酸（DOPAC）/多巴胺）和ALDH活性（DOPAC/DOPAL）（P=0.0025，P=0.036），并增加了DOPAL水平（P=0.04）。大鼠鱼藤酮模型涉及复制PD壳核中发现的模式的儿茶酚胺能神经元的功能异常。这些包括囊泡储存缺陷、ALDH活性降低和DOPAL积聚。大鼠鱼藤酮模型为研究儿茶醛假说提供了一个合适的体内平台。总结：这项研究提出了一种动物模型，反映了帕金森病患者的神经化学模式，新的和不断发展的疾病的儿茶醛假说的基础。
Recent reports indicate that Parkinson's disease (PD) involves specific functional abnormalities in residual neurons – decreased vesicular sequestration of cytoplasmic catecholamines via the vesicular monoamine transporter (VMAT) and decreased aldehyde dehydrogenase (ALDH) activity. This double hit builds up the autotoxic metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL), the focus of the catecholaldehyde hypothesis for the pathogenesis of PD. An animal model is needed that reproduces this abnormal catecholamine neurochemical pattern. Adult rats received subcutaneous vehicle or the mitochondrial complex 1 inhibitor rotenone (2 mg/kg/day via a minipump) for 10 days. Locomotor activity was recorded, and striatal tissue sampled for catechol contents and catechol ratios that indicate the above abnormalities. Compared to vehicle, rotenone reduced locomotor activity (P=0.002), decreased tissue dopamine concentrations (P=0.00001), reduced indices of vesicular sequestration (3,4-dihydroxyphenylacetic acid (DOPAC)/dopamine) and ALDH activity (DOPAC/DOPAL) (P=0.0025, P=0.036), and increased DOPAL levels (P=0.04). The rat rotenone model involves functional abnormalities in catecholaminergic neurons that replicate the pattern found in PD putamen. These include a vesicular storage defect, decreased ALDH activity and DOPAL build-up. The rat rotenone model provides a suitable in vivo platform for studying the catecholaldehyde hypothesis. Summary: This study presents an animal model that reflects the neurochemical pattern found in Parkinson's patients, the basis of the new and evolving catecholaldehyde hypothesis for the disease.
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影响因子：
15.1
作者：
Molochnikov L;Rabey JM;Dobronevsky E;Bonucelli U;Ceravolo R;Frosini D;Grünblatt E;Riederer P;Jacob C;Aharon-Peretz J;Bashenko Y;Youdim MB;Mandel SA
通讯作者：
Mandel SA
影响因子：
6.1
作者：
Galter, D;Buervenich, S;Olson, L
通讯作者：
Olson, L
帕金森病中有毒多巴胺代谢物 DOPAL 积累的决定因素。
影响因子：
4.7
作者：
Goldstein DS;Sullivan P;Holmes C;Miller GW;Alter S;Strong R;Mash DC;Kopin IJ;Sharabi Y
通讯作者：
Sharabi Y
影响因子：
4.6
作者：
Plotegher N;Berti G;Ferrari E;Tessari I;Zanetti M;Lunelli L;Greggio E;Bisaglia M;Veronesi M;Girotto S;Dalla Serra M;Perego C;Casella L;Bubacco L
通讯作者：
Bubacco L
DOI：
10.1124/jpet.118.248492
发表时间：
2018-07-01
影响因子：
3.5
作者：
Jinsmaa, Yunden;Sharabi, Yehonatan;Goldstein, David S.
通讯作者：
Goldstein, David S.