Naumova Alexandra A, Oleynik Ekaterina A, Khramtsova Anna V, Nikolaeva Svetlana D, Chernigovskaya Elena V, Glazova Margarita V
Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, St. Petersburg, Russia.
Dev Neurobiol. 2023 Jul-Sep;83(5-6):205-218. doi: 10.1002/dneu.22924. Epub 2023 Jul 24.
The nigrostriatal system composed of the dorsal striatum and the substantia nigra (SN) is highly involved in the control of motor behavior. Various extremal and pathological conditions as well as social isolation (SI) may cause an impairment of locomotor function; however, corresponding alterations in the nigrostriatal dopaminergic pathway are far from full understanding. Here, we analyzed the effect of 3-day hindlimb unloading (HU) and SI on the key players of dopamine transmission in the nigrostriatal system of CD1 mice. Three groups of mice were analyzed: group-housed (GH), SI, and HU animals. Our data showed a significant decrease in the expression and phosphorylation of tyrosine hydroxylase (TH) in the SN and dorsal striatum of HU mice that suggested attenuation of dopamine synthesis in response to HU. In the dorsal striatum of HU mice, the downregulation of TH expression was also observed indicating the effect of unloading; however, TH phosphorylation at Ser40 was mainly affected by SI pointing on an impact of isolation too. Expression of dopamine receptors D1 in the dorsal striatum of HU mice was increased suggesting a compensatory response, but the activity of downstream signaling pathways involving protein kinase A and cAMP response element-binding protein was inhibited. At the same time, SI alone did not affect expression of DA receptors and activity of downstream signaling in the dorsal striatum. Obtained data let us to conclude that HU was the main factor which impaired dopamine transmission in the nigrostriatal system but SI made some contribution to its negative effects.
由背侧纹状体和黑质（SN）组成的黑质纹状体系统高度参与运动行为的控制。各种极端和病理状况以及社会隔离（SI）可能会导致运动功能受损；然而，黑质纹状体多巴胺能通路的相应改变尚不完全清楚。在此，我们分析了3天的后肢卸载（HU）和SI对CD1小鼠黑质纹状体系统中多巴胺传递关键因子的影响。分析了三组小鼠：群居（GH）、SI和HU组动物。我们的数据显示，HU小鼠的黑质和背侧纹状体中酪氨酸羟化酶（TH）的表达和磷酸化显著降低，这表明对HU的反应中多巴胺合成减弱。在HU小鼠的背侧纹状体中，也观察到TH表达下调，表明卸载的影响；然而，Ser40处的TH磷酸化主要受SI影响，也表明隔离的影响。HU小鼠背侧纹状体中多巴胺受体D1的表达增加，表明存在代偿反应，但涉及蛋白激酶A和cAMP反应元件结合蛋白的下游信号通路的活性受到抑制。同时，单独的SI并不影响背侧纹状体中多巴胺受体的表达和下游信号的活性。获得的数据使我们得出结论，HU是损害黑质纹状体系统中多巴胺传递的主要因素，但SI对其负面影响也有一定作用。
