Purkinje cell injury, structural plasticity and fusion in patients with Friedreich's ataxia.
Purkinje cell injury, structural plasticity and fusion in patients with Friedreich's ataxia.
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DOI：
10.1186/s40478-016-0326-3
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发表时间：
2016-05-23
影响因子：
7.1
通讯作者：
Wilkins A
中科院分区：
文献类型：
--
作者：
Kemp KC;Cook AJ;Redondo J;Kurian KM;Scolding NJ;Wilkins A
浦肯野细胞病理学是一系列遗传性和获得性小脑疾病的常见发现，浦肯野细胞损伤的程度取决于潜在的病因。浦肯野细胞具有无与伦比的抗损伤能力，并在中枢神经系统内显示出独特的再生能力。它们对细胞损伤的反应不是大多数神经元的典型反应，可能代表了退行性、代偿性和再生机制。在这里，我们提出了一个病理学研究显示新的和基本的见解浦肯野细胞损伤，重塑和修复弗里德赖希共济失调，最常见的遗传性共济失调。分析尸检小脑组织的患者谁弗里德赖希共济失调，我们提供的证据显着损伤浦肯野细胞轴突室相对保存的核周体和广泛的树突状分支。浦肯野细胞的轴突重塑在疾病中明显升高。在遗传条件下，我们还首次显示了Friedreich共济失调病例中浦肯野细胞融合和异核体形成频率的疾病相关增加;有证据表明小脑炎症的潜在水平影响异核体形成。我们的研究结果进一步证明了浦肯野细胞独特的可塑性和再生潜力。阐明这些现象背后的生物学机制可能对操纵神经元修复以响应神经损伤具有重要的临床意义。
Purkinje cell pathology is a common finding in a range of inherited and acquired cerebellar disorders, with the degree of Purkinje cell injury dependent on the underlying aetiology. Purkinje cells have an unparalleled resistance to insult and display unique regenerative capabilities within the central nervous system. Their response to cell injury is not typical of most neurons and likely represents both degenerative, compensatory and regenerative mechanisms. Here we present a pathological study showing novel and fundamental insights into Purkinje cell injury, remodelling and repair in Friedreich’s ataxia; the most common inherited ataxia. Analysing post-mortem cerebellum tissue from patients who had Friedreich's ataxia, we provide evidence of significant injury to the Purkinje cell axonal compartment with relative preservation of both the perikaryon and its extensive dendritic arborisation. Axonal remodelling of Purkinje cells was clearly elevated in the disease. For the first time in a genetic condition, we have also shown a disease-related increase in the frequency of Purkinje cell fusion and heterokaryon formation in Friedreich's ataxia cases; with evidence that underlying levels of cerebellar inflammation influence heterokaryon formation. Our results together further demonstrate the Purkinje cell’s unique plasticity and regenerative potential. Elucidating the biological mechanisms behind these phenomena could have significant clinical implications for manipulating neuronal repair in response to neurological injury.