Kalinina Daria S, Lyakhovetskii Vsevolod A, Gorskii Oleg V, Shkorbatova Polina Yu, Pavlova Natalia V, Bazhenova Elena Yu, Sysoev Yurii I, Gainetdinov Raul R, Musienko Pavel E
Institute of Translational Biomedicine, St. Petersburg State University Hospital, St. Petersburg State University, 199034 St. Petersburg, Russia.
Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 194223 St. Petersburg, Russia.
Biomedicines. 2023 Jul 11;11(7):1958. doi: 10.3390/biomedicines11071958.
Dopamine (DA) is the critical neurotransmitter involved in the unconscious control of muscle tone and body posture. We evaluated the general motor capacities and muscle responses to postural disturbance in three conditions: normal DA level (wild-type rats, WT), mild DA deficiency (WT after administration of α-methyl-p-tyrosine-AMPT, that blocks DA synthesis), and severe DA depletion (DAT-KO rats after AMPT). The horizontal displacements in WT rats elicited a multi-component EMG corrective response in the flexor and extensor muscles. Similar to the gradual progression of DA-related diseases, we observed different degrees of bradykinesia, rigidity, and postural instability after AMPT. The mild DA deficiency impaired the initiation pattern of corrective responses, specifically delaying the extensor muscles' activity ipsilaterally to displacement direction and earlier extensor activity from the opposite side. DA depletion in DAT-KO rats after AMPT elicited tremors, general stiffness, and akinesia, and caused earlier response to horizontal displacements in the coactivated flexor and extensor muscles bilaterally. The data obtained show the specific role of DA in postural reactions and suggest that this experimental approach can be used to investigate sensorimotor control in different dopamine-deficient states and to model DA-related diseases.
多巴胺(DA)是参与无意识控制肌张力和身体姿势的关键神经递质。我们在三种情况下评估了一般运动能力和肌肉对姿势干扰的反应:正常DA水平(野生型大鼠,WT)、轻度DA缺乏(给予α-甲基-对-酪氨酸-AMPT后阻断DA合成的WT大鼠)和严重DA耗竭(AMPT后的DAT-KO大鼠)。WT大鼠的水平位移在屈肌和伸肌中引发了多成分肌电图纠正反应。与DA相关疾病的逐渐进展相似,我们在AMPT后观察到不同程度的运动迟缓、僵硬和姿势不稳。轻度DA缺乏损害了纠正反应的起始模式,特别是延迟了与位移方向同侧的伸肌活动,并使对侧的伸肌活动提前。AMPT后DAT-KO大鼠的DA耗竭引发了震颤、全身僵硬和运动不能,并导致双侧共同激活的屈肌和伸肌对水平位移的反应提前。获得的数据显示了DA在姿势反应中的特定作用,并表明这种实验方法可用于研究不同多巴胺缺乏状态下的感觉运动控制,并模拟与DA相关的疾病。