Peripheral neuropathy in the pre-diabetic state of the type 2 diabetes mouse model (TSOD mice) involves TRPV1 expression in dorsal root ganglions.

2 型糖尿病小鼠模型 （ TSOD 小鼠 ） 的糖尿病前期状态下的周围神经病变涉及背根神经节中的 TRPV1 表达。

• 发表时间: Jun 2022
• 来源期刊: IBRO Neurosci Rep
• DOI: 10.1016/j.ibneur.2022.02.001
• PMID: 35199097
• 文章类型: Journal Article
• 作者列表: Shida K,Ohsawa M,Takahashi S,Ota H,Tamura T,Kusama N,Nakasone M,Yamazaki H,Sobue K,Shida K,Ohsawa M,Takahashi S,Ota H,Tamura T,Kusama N,Nakasone M,Yamazaki H,Sobue K

关键词: ANOVA, Analysis of variance; DM, diabetes mellitus; DRG, dorsal root ganglion; Diabetes mellitus; FITC, fluorescein isothiocyanate; HFD, High-Fat Diet; IGT, impaired glucose tolerance; ITT, insulin tolerance test; Impaired glucose tolerance; LPA, Lysophosphatidic Acid; Mechanical allodynia; NF-H, neurofilament heavy; STZ, streptozotocin; TRITC, tetramethylrhodamine; TRPV1, Transient Receptor Potential Vanilloid 1; TSNO, Tsumura Suzuki Non-Obesity; TSOD, Tsumura Suzuki Obese Diabetes; Thermal hypersensitivity; ir, immunoreactive; tHODE, total Hydroxyoctadecadienoic Acid; ANOVA, Analysis of variance; DM, diabetes mellitus; DRG, dorsal root ganglion; Diabetes mellitus; FITC, fluorescein isothiocyanate; HFD, High-Fat Diet; IGT, impaired glucose tolerance; ITT, insulin tolerance test; Impaired glucose tolerance; LPA, Lysophosphatidic Acid; Mechanical allodynia; NF-H, neurofilament heavy; STZ, streptozotocin; TRITC, tetramethylrhodamine; TRPV1, Transient Receptor Potential Vanilloid 1; TSNO, Tsumura Suzuki Non-Obesity; TSOD, Tsumura Suzuki Obese Diabetes; Thermal hypersensitivity; ir, immunoreactive; tHODE, total Hydroxyoctadecadienoic Acid

Abstract

Peripheral neuropathy, which is a complication of diabetes mellitus (DM), is thought to occur in the pre-DM state, being known as impaired glucose tolerance (IGT) neuropathy, although its pathogenesis is unknown. Since it is reversible, an effective treatment at the pre-DM stage could stop the progression of peripheral neuropathy and improve patients\' quality of life and reduce medical costs. We investigated the hypersensitivity to mechanical and thermal stimuli during the pre-DM state in Tsumura Suzuki Obese Diabetes (TSOD) mice, a type 2 DM mouse model. The expression pattern of the Transient Receptor Potential Vanilloid 1 (TRPV1)-positive cells in the dorsal root ganglia (DRG) was examined in TSOD mice, which showed a pre-DM state at 5-12 weeks of age and decreased mechanical and thermal nociceptive thresholds. Additionally, the size of TRPV1-positive cells in TSOD mice increased compared with that in non-diabetic controls (Tsumura Suzuki Non-Obesity; TSNO). Furthermore, the expression of TRPV1 on myelinated nerve fibers (neurofilament heavy-positive cells) had significantly increased. Thus, TSOD mice in the pre-DM state at 5-12 weeks of age could be a useful animal model of IGT neuropathy. We also hypothesized that the development of IGT neuropathy may involve a switch in TRPV1 expression from small, unmyelinated neurons to large, myelinated neurons in the DRG.

摘要

周围神经病变,这是糖尿病（DM）的并发症，被认为发生在DM前状态，被称为糖耐量受损（IGT）神经病，虽然其发病机制尚不清楚。因为它是可逆的，DM前期的有效治疗可以阻止周围神经病变的进展,改善患者的生活质量,降低医疗成本.我们研究了TsumuraSuzukiObeseDiabetes（TSOD）小鼠在DM前状态下对机械和热刺激的超敏反应，2型DM小鼠模型。在TSOD小鼠中检查了背根神经节（DRG）中瞬时受体电位香草素1（TRPV1）阳性细胞的表达模式，在5-12周龄时显示出DM前状态，并降低了机械和热伤害感受阈值。此外,与非糖尿病对照组相比，TSOD小鼠中TRPV1阳性细胞的大小增加（TsumuraSuzuki非肥胖；TSNO）。此外，TRPV1在有髓神经纤维(神经丝重阳性细胞)上的表达显著增加.因此，在5-12周龄时处于DM前状态的TSOD小鼠可以是IGT神经病变的有用动物模型。我们还假设IGT神经病变的发展可能涉及TRPV1表达从小,无髓鞘神经元大，DRG中的有髓神经元。