Serotonin innervation of the subthalamic nucleus in parkinsonian monkeys

IF 5.1 2区医学 Q1 NEUROSCIENCES

Neurobiology of Disease Pub Date : 2025-05-02 DOI:10.1016/j.nbd.2025.106938

C.V.L. Delmas , J. Munro , M. Bérard , T. Di Paolo , M. Morissette , M.E. Tremblay , A. Parent , M. Parent

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Abstract

The subthalamic nucleus (STN), the main driving force of the basal ganglia, is innervated by brainstem serotonin (5-HT) neurons with highly plastic axonal arborization. A pathologically-induced rearrangement of the ascending 5-HT projections could contribute to the disrupted firing pattern of STN neurons observed in Parkinson's disease (PD). This light and electron microscope study was designed to characterize the neuroadaptive changes of 5-HT inputs to the different functional territories of the STN in four cynomolgus monkeys (Macaca fascicularis) rendered parkinsonian by systemic injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and four control animals. Using an unbiased stereological approach, we report a significant decrease of the density of 5-HT axon varicosities immunolabeled for the 5-HT membrane transporter (SERT), across all STN functional territories of MPTP-treated monkeys. In MPTP-treated animals, the SERT+ axon varicosities are larger than in control monkeys. In both experimental conditions they are only partially synaptic. A preserved length of 5-HT axons in the STN along with a conserved number of 5-HT neurons in the dorsal raphe nucleus is observed. Overall, our results indicate that, in parkinsonian monkeys, the 5-HT axons projecting to the STN are preserved but endowed with significantly less axon varicosities. Such neuroadaptive change could lead to a lower ambient level of 5-HT in this basal ganglia component, representing a compensatory mechanism designed to cope with the hyperexcitability of STN neurons that is known to occur in PD.

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帕金森猴丘脑下核的血清素神经支配

丘脑下核（STN）是基底神经节的主要驱动力，由脑干5-羟色胺（5-HT）神经元支配，具有高度可塑性的轴突树突。病理诱导的上升5-HT投射重排可能导致帕金森病（PD）中观察到的STN神经元放电模式中断。本研究旨在通过全身注射1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP），观察4只食猴（Macaca fascicularis）和4只对照动物帕金森病后，5-羟色胺输入到STN不同功能区域的神经适应性变化。使用无偏体视学方法，我们报告了在mptp治疗的猴子的所有STN功能区域中，5-HT膜转运蛋白（SERT）免疫标记的5-HT轴突变异密度显著降低。在mptp治疗的动物中，SERT+轴突变异比对照猴子大。在这两种实验条件下，它们只是部分突触。在中缝背核中，5-HT轴突的长度和5-HT神经元的数量保持不变。总的来说，我们的研究结果表明，在帕金森猴中，向STN投射的5-HT轴突被保留了下来，但轴突的多样性明显减少。这种神经适应性变化可能导致基底神经节成分中5-羟色胺的环境水平降低，这代表了一种补偿机制，旨在应对PD中已知发生的STN神经元的过度兴奋性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neurobiology of Disease 医学-神经科学

CiteScore

11.20

自引率

3.30%

发文量

270

审稿时长

76 days

期刊介绍： Neurobiology of Disease is a major international journal at the interface between basic and clinical neuroscience. The journal provides a forum for the publication of top quality research papers on: molecular and cellular definitions of disease mechanisms, the neural systems and underpinning behavioral disorders, the genetics of inherited neurological and psychiatric diseases, nervous system aging, and findings relevant to the development of new therapies.