Wang Shuang, Zhao Yan, Gao Jie, Guo Yufang, Wang Xiang, Huo Jian, Wei Ping, Cao Jian
1 Department of Pathophysiology, Institute of Basic Medical Science, Xi'an Medical University, Xi'an, China.
2 Department of Immunology, Institute of Basic Medical Science, Xi'an Medical University, Xi'an, China.
Am J Alzheimers Dis Other Demen. 2017 Mar;32(2):73-81. doi: 10.1177/1533317516685425. Epub 2017 Jan 13.
The 5-hydroxytryptamine (5-HT; serotonin) neurotransmission is severely affected by the degeneration of nigrostriatal dopaminergic neurons. Here, we report the effects of the systemic administration of the 5-HT receptor agonist AS-19. In sham rats, the mean response of the 5-HT neurons in the dorsal raphe nucleus (DRN) to systemic AS-19 was excitatory and the mean response of the γ-aminobutyric acid (GABA) interneurons was inhibitory. In Parkinson disease (PD) rats, the same dose did not affect the 5-HT neurons and only high doses (640 μg/kg intravenous) were able to the increase GABA interneuron activity. These results indicate that DRN 5-HT neurons and GABA interneurons are regulated by the activation of 5-HT receptors and that the degeneration of the nigrostriatal pathway leads to decreased responses of these neurons to AS-19, which in turn suggests that the 5-HT receptors on 5-HT neurons and GABA interneurons in PD rats are dysfunctional and downregulated.
5-羟色胺（5-HT；血清素）神经传递受到黑质纹状体多巴胺能神经元变性的严重影响。在此，我们报告了5-HT受体激动剂AS-19全身给药的效果。在假手术大鼠中，中缝背核（DRN）中5-HT神经元对全身给予AS-19的平均反应是兴奋性的，而γ-氨基丁酸（GABA）中间神经元的平均反应是抑制性的。在帕金森病（PD）大鼠中，相同剂量不影响5-HT神经元，只有高剂量（静脉注射640μg/kg）能够增加GABA中间神经元的活性。这些结果表明，DRN中的5-HT神经元和GABA中间神经元受5-HT受体激活的调节，黑质纹状体通路的变性导致这些神经元对AS-19的反应降低，这反过来表明PD大鼠中5-HT神经元和GABA中间神经元上的5-HT受体功能失调且下调。
