关键词: Acetylcholine Deep brain stimulation Dopamine Magnetoelectric nanoparticles Serotonin

Mesh : Mice Animals Subthalamic Nucleus / metabolism Deep Brain Stimulation / methods Pedunculopontine Tegmental Nucleus / metabolism Thalamus / metabolism Proto-Oncogene Proteins c-fos / metabolism Movement Disorders

来  源:   DOI:10.1016/j.bbr.2023.114363

Abstract:
Deep brain stimulation (DBS) is commonly used to alleviate motor symptoms in several movement disorders. However, the procedure is invasive, and the technology has remained largely stagnant since its inception decades ago. Recently, we have shown that wireless nanoelectrodes may offer an alternative approach to conventional DBS. However, this method is still in its infancy, and more research is required to characterize its potential before it can be considered as an alternative to conventional DBS.
Herein, we aimed to investigate the effect of stimulation via magnetoelectric nanoelectrodes on primary neurotransmitter systems that have implications for DBS in movement disorders.
Mice were injected with either magnetoelectric nanoparticles (MENPs) or magnetostrictive nanoparticles (MSNPs, as a control) in the subthalamic nucleus (STN). Mice then underwent magnetic stimulation, and their motor behavior was assessed in the open field test. In addition, magnetic stimulation was applied before sacrifice and post-mortem brains were processed for immunohistochemistry (IHC) to assess the co-expression of c-Fos with either tyrosine hydroxylase (TH), tryptophan hydroxylase-2 (TPH2) or choline acetyltransferase (ChAT).
Stimulated animals covered longer distances in the open field test when compared to controls. Moreover, we found a significant increase in c-Fos expression in the motor cortex (MC) and paraventricular region of the thalamus (PV-thalamus) after magnetoelectric stimulation. Stimulated animals showed fewer TPH2/c-Fos double-labeled cells in the dorsal raphe nucleus (DRN), as well as TH/c-Fos double-labeled cells in the ventral tegmental area (VTA), but not in the substantia nigra pars compacta (SNc). There was no significant difference in the number of ChAT/ c-Fos double-labeled cells in the pedunculopontine nucleus (PPN).
Magnetoelectric DBS in mice enables selective modulation of deep brain areas and animal behavior. The measured behavioral responses are associated with changes in relevant neurotransmitter systems. These changes are somewhat similar to those observed in conventional DBS, suggesting that magnetoelectric DBS might be a suitable alternative.
摘要:
背景:深部脑刺激(DBS)通常用于缓解几种运动障碍的运动症状。然而,这个程序是侵入性的,这项技术自几十年前诞生以来基本上停滞不前。最近,我们已经表明,无线纳米电极可以提供传统DBS的替代方法。然而,这种方法还处于起步阶段,并且需要更多的研究来表征其潜力,然后才能将其视为常规DBS的替代品。
目的:在此,我们旨在研究通过磁电纳米电极刺激对主要神经递质系统的影响,这对运动障碍中的DBS有影响。
方法:小鼠注射磁电纳米粒子(MENP)或磁致伸缩纳米粒子(MSNP,作为对照)在丘脑底核(STN)中。然后对小鼠进行磁刺激,并在开场试验中评估了他们的运动行为。此外,在处死前施加磁刺激,并对死后的大脑进行免疫组织化学(IHC)处理,以评估c-Fos与酪氨酸羟化酶(TH)的共表达,色氨酸羟化酶-2(TPH2)或胆碱乙酰转移酶(ChAT)。
结果:与对照组相比,在野外测试中,受激动物的距离更长。此外,我们发现,磁电刺激后,运动皮质(MC)和丘脑室旁区(PV-丘脑)的c-Fos表达显著增加.受刺激的动物在背侧中缝核(DRN)中显示出较少的TPH2/c-Fos双标记细胞,以及腹侧被盖区(VTA)的TH/c-Fos双标记细胞,但不在黑质致密部(SNc)中。花梗桥脑核(PPN)中ChAT/c-Fos双标记细胞的数量没有显着差异。
结论:在小鼠中的磁电DBS能够选择性调节脑深部区域和动物行为。测量的行为反应与相关神经递质系统的变化相关。这些变化与常规DBS中观察到的变化有些相似,这表明磁电DBS可能是一个合适的替代方案。
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