Centre for NeuroInflammation & Neurodegeneration, Division of Brain Sciences, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, United Kingdom.
Exp Neurol. 2013 Oct;248:213-23. doi: 10.1016/j.expneurol.2013.06.008. Epub 2013 Jun 14.
The pedunculopontine nucleus (PPN) controls various physiological functions, whilst being deemed a suitable target for low-frequency stimulation therapy for alleviating aspects of Parkinson's disease (PD). Previous studies showed that the PPN contains mainly cholinergic, γ-aminobutyric acid (GABA)ergic and glutamatergic neurons. Here we report on the total number of PPN neurons in laboratory rats, a species frequently used as an experimental model for simulating aspects of human PD. Moreover, the study reports that the number of PPN neurons decreases under toxic conditions that mimic in animals the core pathology seen in human PD. Immunohistochemical detection methods combined with unbiased stereology served to estimate that the PPN of healthy rats unilaterally contains ~19,028 NeuN-immunopositive neurons. The identified neurons revealed a distinct distribution pattern consisting of high cell density in the most rostral and caudal sections of the PPN nucleus, contrasting with lower densities in the medial segments. Our data also show a significant loss which affected PPN non-cholinergic cells, but not cholinergic ones in rats lesioned unilaterally in the Substantia Nigra pars compacta (SNpc) with a single injection of 6-hydroxydopamine (6-OHDA) compared to control animals. This result differs from previous studies which reported a substantial cholinergic cell loss in the PPN of post-mortem PD brains and in 6-OHDA-lesioned monkeys. Since a noted demise of dopaminergic neurons residing in the SN was confirmed in the 6-OHDA-lesioned rats, the current study suggests that a "dying-back" mechanism may underlie the cell death affecting non-cholinergic PPN neurons.
被盖脚桥核（PPN）控制着各种生理功能，同时被认为是低频刺激疗法的一个合适靶点，可用于缓解帕金森病（PD）的某些方面。先前的研究表明，PPN 主要包含胆碱能、γ-氨基丁酸（GABA）能和谷氨酸能神经元。在这里，我们报告了实验室大鼠 PPN 神经元的总数，大鼠是一种常用于模拟人类 PD 某些方面的实验模型的物种。此外，该研究报告称，在模拟动物中人类 PD 核心病理学的有毒条件下，PPN 神经元的数量会减少。免疫组织化学检测方法与无偏立体学相结合，用于估计健康大鼠单侧 PPN 含有约 19028 个 NeuN 免疫阳性神经元。鉴定出的神经元呈现出一种独特的分布模式，在 PPN 核的最头侧和尾侧部分细胞密度较高，而在中侧部分密度较低。我们的数据还显示，与对照组动物相比，单侧黑质致密部（SNpc）用 6-羟多巴胺（6-OHDA）单次注射损伤的大鼠 PPN 中非胆碱能细胞而非胆碱能细胞显著减少。这一结果与先前的研究不同，先前的研究报告称，帕金森病死后大脑 PPN 中的胆碱能细胞大量丧失，以及 6-OHDA 损伤的猴子中也是如此。由于在 6-OHDA 损伤的大鼠中证实了 SN 中多巴胺能神经元的明显丧失，因此目前的研究表明，“逆行性”机制可能是影响非胆碱能 PPN 神经元死亡的原因。
