■5-羟色胺(5-HT)系统可以操纵DA去神经支配的纹状体中外源性L-DOPA的加工,导致L-DOPA诱导的运动障碍(LID)的调节。
■为了表征5-羟色胺前体5-羟基色氨酸(5-HTP)或5-羟色胺转运蛋白(SERT)抑制剂的作用,西酞普兰对L-DOPA诱导的行为,神经化学信号,以及帕金森病动物模型中潜在的蛋白质表达。
■20周龄的MitoPark(MP)小鼠,接受14天的L-DOPA/卡比多巴给药,表现出运动障碍,称为LID。随后的调查探索了5-HT改性剂的作用,如5-HTP和西酞普兰,关于异常非自愿运动(AIM),运动活动,神经化学信号,血清素转运蛋白活性,LIDMP小鼠的DA-去神经支配纹状体中的蛋白质表达。
■5-HTP对发展和确定的LID表现出持续时间依赖性抑制作用,特别是与在L-DOPA引发的MP小鼠中观察到的异常肢体运动有关。然而,西酞普兰,在LIDMP小鼠中主要抑制由L-DOPA诱导的异常轴向运动。我们证明5-HTP可以降低DA周转率的L-DOPA上调,同时上调5-HT代谢。此外,5-HTP显示降低LIDMP小鼠纹状体中p-ERK和p-DARPP-32的表达。西酞普兰在缓解LID发育中的作用可能归因于LIDMP小鼠背侧纹状体中SERT活性的下调。
■虽然单次注射5-HTP和西酞普兰均有效缓解了LID的发展,AIM亚型缓解的差异可能与这两种5-羟色胺能药物对L-DOPA衍生的DA和5-HT代谢的独特作用有关.
UNASSIGNED: The serotonin (5-HT) system can manipulate the processing of exogenous L-DOPA in the DA-denervated striatum, resulting in the modulation of L-DOPA-induced dyskinesia (LID).
UNASSIGNED: To characterize the effects of the serotonin precursor 5-hydroxy-tryptophan (5-HTP) or the serotonin transporter (SERT) inhibitor, Citalopram on L-DOPA-induced behavior, neurochemical signals, and underlying protein expressions in an animal model of Parkinson\'s disease.
UNASSIGNED: MitoPark (MP) mice at 20 weeks of age, subjected to a 14-day administration of L-DOPA/
Carbidopa, displayed dyskinesia, referred to as LID. Subsequent investigations explored the effects of 5-HT-modifying agents, such as 5-HTP and Citalopram, on abnormal involuntary movements (AIMs), locomotor activity, neurochemical signals, serotonin transporter activity, and protein expression in the DA-denervated striatum of LID MP mice.
UNASSIGNED: 5-HTP exhibited duration-dependent suppressive effects on developing and established LID, especially related to abnormal limb movements observed in L-DOPA-primed MP mice. However, Citalopram, predominantly suppressed abnormal axial movement induced by L-DOPA in LID MP mice. We demonstrated that 5-HTP could decrease L-DOPA-upregulation of DA turnover rates while concurrently upregulating 5-HT metabolism. Additionally, 5-HTP was shown to reduce the expressions of p-ERK and p-DARPP-32 in the striatum of LID MP mice. The effect of Citalopram in alleviating LID development may be attributed to downregulation of SERT activity in the dorsal striatum of LID MP mice.
UNASSIGNED: While both single injection of 5-HTP and Citalopram effectively mitigated the development of LID, the difference in mitigation of AIM subtypes may be linked to the unique effects of these two serotonergic agents on L-DOPA-derived DA and 5-HT metabolism.