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Dopamine Synthesis by Non-Dopaminergic Neurons in the Stratium of Mice with and without Degeneration of the Nigrostriatal Dopaminergic System
Neurochemical Journal ( IF 0.5 ) Pub Date : 2020-03-31 , DOI: 10.1134/s1819712420010043
V. E. Blokhin , T. S. Pronina , M. V. Ugryumov

Abstract—In the past 15 years, it has been shown that dopamine (DA) is synthesized in the brain not only by dopaminergic neurons but also by non-dopaminergic neurons expressing one of the complementary enzymes tyrosine hydroxylase or aromatic L-amino acid decarboxylase (hereinafter, decarboxylase). Moreover, L-DOPA, an intermediate product of DA synthesis, is transported from neurons containing tyrosine hydroxylase to neurons containing decarboxylase. The aim of this work was to test our hypothesis about the presence of DA synthesis by non-dopaminergic neurons in the murine striatum, a key link in the central regulation of motor function. For this, we used a methodological approach we developed that allows us to determine the intensity of cooperative synthesis as the difference between the total DA content in brain slices and in the incubation medium after incubation of the slices in Krebs–Ringer solution and Krebs–Ringer solution with the addition of a competitive L-DOPA membrane carrier inhibitor. Synthetic non-metabolizable 2-amino-2-norbornanecarboxylic acid, which, unlike the previously used inhibitors (L-tyrosine, L-leucine, etc.), does not directly or indirectly affect the functional activity of DA-ergic neurons, was used as an inhibitor for the first time. The use of this inhibitor made it possible to obtain evidence that the DA contained in the striatum of mice is normally synthesized not only by DAergic neurons (in axons), but also by non-dopaminergic neurons that express either tyrosine hydroxylase or decarboxylase. It was also shown that DA synthesis by non-dopaminergic neurons is performed in the striatum of mice with partial DAergic denervation caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a specific neurotoxin. We believe that the synthesis of DA by non-dopaminergic neuronsis an important neuroplasticity mechanism which contributes to the compensation of DA deficiency after the degeneration of nigrostriatal DA-ergic neurons. Thus, for the first time, evidence was obtained for the synthesis of DA by non-dopaminergic neurons in the striatum of healthy mice and mice with DA-ergic denervation of the striatum.

中文翻译:

具有和不具有黑质纹状体多巴胺能系统变性的小鼠中非多巴胺能神经元的多巴胺合成

摘要—在过去的15年中,研究表明,多巴胺(DA)不仅在大脑中由多巴胺能神经元合成,而且还由表达互补酶酪氨酸羟化酶或芳香族L-氨基酸脱羧酶之一的非多巴胺能神经元合成(以下简称“多巴胺能”)。 ,脱羧酶)。此外,DA合成的中间产物L-DOPA从含有酪氨酸羟化酶的神经元转运到含有脱羧酶的神经元。这项工作的目的是检验我们的假设,即鼠纹状体中非多巴胺能神经元是否存在DA合成,这是运动功能中枢调节的关键环节。为了这,我们使用开发的方法学方法,可以确定合作合成的强度,方法是将切片在Krebs-Ringer溶液和Krebs-Ringer溶液中分别与脑切片和培养液中的DA含量之差确定。加入竞争性L-DOPA膜载体抑制剂。使用了合成的不可代谢的2-氨基-2-降冰片烷羧酸,它与以前使用的抑制剂(L-酪氨酸,L-亮氨酸等)不同,它不会直接或间接影响DA-能神经元的功能活性第一次成为抑制剂。使用这种抑制剂可以获得证据,证明小鼠纹状体中的DA通常不仅由DA能神经元(在轴突中)合成,但也可以由表达酪氨酸羟化酶或脱羧酶的非多巴胺能神经元引起。还显示非多巴胺能神经元的DA合成是在小鼠纹状体中进行的,该小鼠的纹状体具有由1-甲基-4-苯基-1,2,3,6-四氢吡啶(一种特定的神经毒素)引起的部分DA能神经支配化。我们认为,非多巴胺能神经元合成DA的重要神经可塑性机制,有助于补偿黑纹状体DA能神经元变性后DA的缺乏。因此,首次获得了健康小鼠和纹状体的DA-能神经支配的小鼠的纹状体中非多巴胺能神经元合成DA的证据。还显示非多巴胺能神经元的DA合成是在小鼠纹状体中进行的,该小鼠的纹状体具有由1-甲基-4-苯基-1,2,3,6-四氢吡啶(一种特定的神经毒素)引起的部分DA能神经支配化。我们认为,非多巴胺能神经元合成DA的重要神经可塑性机制,有助于补偿黑纹状体DA能神经元变性后DA的缺乏。因此,首次获得了健康小鼠和纹状体的DA-能神经支配的小鼠的纹状体中非多巴胺能神经元合成DA的证据。还显示非多巴胺能神经元的DA合成是在小鼠纹状体中进行的,该小鼠的纹状体具有由1-甲基-4-苯基-1,2,3,6-四氢吡啶(一种特定的神经毒素)引起的部分DA能神经支配化。我们认为,非多巴胺能神经元合成DA的重要神经可塑性机制,有助于补偿黑纹状体DA能神经元变性后DA的缺乏。因此,首次获得了健康小鼠和纹状体的DA-能神经支配的小鼠的纹状体中非多巴胺能神经元合成DA的证据。我们认为,非多巴胺能神经元合成DA的重要神经可塑性机制,有助于补偿黑纹状体DA能神经元变性后DA的缺乏。因此,首次获得了健康小鼠和纹状体的DA-能神经支配的小鼠的纹状体中非多巴胺能神经元合成DA的证据。我们认为,非多巴胺能神经元合成DA的重要神经可塑性机制,有助于补偿黑纹状体DA能神经元变性后DA的缺乏。因此,首次获得了健康小鼠和纹状体的DA-能神经支配的小鼠的纹状体中非多巴胺能神经元合成DA的证据。
更新日期:2020-03-31
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