Abstract：
Specialized cutaneous Schwann cells (SCs), termed nociceptive SCs, were recently discovered. Their function is not fully understood, but they are believed not only to support peripheral axons in mouse skin by forming a mesh-like neural-glio networking structure in subepidermal area, but also contributing to transduction of mechanical sensation and neuropathic pain. Diabetic neuropathy (DPN) is one of the most common complication of diabetes, however, the mechanisms behind painful and painless DPN remain unclear. Using a mouse model of DPN, we want to investigate if there are quantitative differences in nociceptive SC density between the condition of hyperglycemia-induced sensory abnormalities and control condition and at which stage in the disease the damage occurs. Here, we developed a set of counting rules for nociceptive SCs based on immunofluorescent staining, and applied the method to quantify the density of nociceptive SCs in control mice (n = 10), mice with nociceptive hypersensitivity at early diabetic stage (n = 5), and mice with sensory hyposensitivity at late diabetic stage (n = 5) in the Streptozotocin (STZ) model of type 1 diabetes. Nociceptive SCs were identified as S100+/Sox10+/DAPI+ cells abutting to peripheral nerves, with the somas located within 25 µm depth in the subepidermal area and outside glands and large fiber bundles. Hypersensitive diabetic mice had decreased nociceptive SC density, despite having normal epidermal nerve fiber density, compared with age-matched control mice (P = 0.023). In contrast, there was a reduction in intraepidermal nerve fiber density but no difference in nociceptive SC density between hyposensitive diabetic mice and the age-matched control mice. This study provides a detailed description of how to identify and quantify nociceptive SC and demonstrates that nociceptive SC density declines before nerve fiber deterioration, which supports previous observations that nociceptive SCs are critical for maintenance of cutaneous sensory nerves.
摘要：
特化皮肤雪旺细胞（SCs），称为伤害性SCs，是最近发现的。它们的功能还没有被完全理解，但是它们被认为不仅通过在表皮下区域形成网状神经胶质网络结构来支持小鼠皮肤中的外周轴突，但也有助于机械感觉和神经性疼痛的传导。糖尿病神经病变(DPN)是糖尿病最常见的并发症之一。然而,疼痛和无痛DPN背后的机制尚不清楚.使用DPN的小鼠模型，我们想调查高血糖引起的感觉异常的状况和控制状况之间的伤害性SC密度是否存在定量差异，以及在疾病的哪个阶段发生损害。这里,我们开发了一套基于免疫荧光染色的伤害性SCs计数规则，并应用该方法量化对照小鼠(n=10)的伤害性SCs密度，在早期糖尿病阶段具有伤害性超敏反应的小鼠（n=5），和在1型糖尿病的链脲佐菌素（STZ）模型中在糖尿病晚期（n=5）具有感觉敏感性的小鼠。伤害性SCs被鉴定为S100+/Sox10+/DAPI+细胞邻接周围神经，体位于表皮下区域和外部腺体和大纤维束的25µm深度内。过敏性糖尿病小鼠的伤害性SC密度降低，尽管表皮神经纤维密度正常,与年龄匹配的对照小鼠相比（P=0.023）。相比之下,在低敏感性糖尿病小鼠和年龄匹配的对照小鼠之间,表皮内神经纤维密度降低,但伤害性SC密度无差异.这项研究提供了如何识别和量化伤害性SC的详细描述，并证明了伤害性SC密度在神经纤维恶化之前下降，这支持了先前的观察，即伤害性SCs对于维持皮肤感觉神经至关重要。
