Kim A R, Pavlova E N, Blokhin V E, Bogdanov V V, Ugrumov M V
Koltzov Institute of Developmental Biology of Russian Academy of Sciences, Moscow,119334 Russia.
Acta Naturae. 2021 Jul-Sep;13(3):106-109. doi: 10.32607/actanaturae.11399.
Early (preclinical) diagnosis of Parkinson's disease (PD) is a major challenge in modern neuroscience. The objective of this study was to experimentally evaluate a diagnostic challenge test with monoiodotyrosine (MIT), an endogenous inhibitor of tyrosine hydroxylase. Striatal dopamine was shown to decrease by 34% 2 h after subcutaneous injection of 100 mg/kg MIT to intact mice, with the effect not being amplified by a further increase in the MIT dose. The selected MIT dose caused motor impairment in a neurotoxic mouse model of preclinical PD, but not in the controls. This was because MIT reduced striatal dopamine to the threshold of motor symptoms manifestation only in PD mice. Therefore, using the experimental mouse model of preclinical PD, we have shown that a MIT challenge test may be used to detect latent nigrostriatal dysfunction.
帕金森病(PD)的早期(临床前)诊断是现代神经科学面临的一项重大挑战。本研究的目的是通过实验评估一种使用酪氨酸羟化酶的内源性抑制剂单碘酪氨酸(MIT)的诊断激发试验。向完整小鼠皮下注射100mg/kg MIT后2小时,纹状体多巴胺显示减少34%,且MIT剂量进一步增加时该效应未被放大。所选的MIT剂量在临床前PD的神经毒性小鼠模型中引起运动障碍,但在对照组中未引起。这是因为MIT仅在PD小鼠中将纹状体多巴胺降低到运动症状表现的阈值。因此,利用临床前PD的实验小鼠模型,我们已经表明MIT激发试验可用于检测潜在的黑质纹状体功能障碍。