Filfilan Reham M, Nassar Mohammed A
School of Biosciences, University of Sheffield, Sheffield, UK.
Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia.
Mol Pain. 2025 Jan-Dec;21:17448069251328521. doi: 10.1177/17448069251328521. Epub 2025 Mar 11.
Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes. Half of DPN patients experience sensory deficits including loss of sensation and pain. Loss of sensation increases the risk of unnoticed foot injuries which combined with poor circulation and healing lead to amputation. Type 2 diabetes accounts for 50% of foot amputation highlighting the significant impact sensory loss can have on patients' quality of life. However, the cellular basis underlying sensory loss in DPN remains unclear. We characterized diabetes-induced neuronal loss and damage in dorsal root ganglia (DRG) in the db/db mouse model of type 2 diabetes. Morphometric characterization was carried out on two neuronal populations in lumbar DRGs of 32-week diabetic (db/db) mice. These are the N200-positive neurons, a marker for low and high-threshold mechanosensitive sensory and proprioceptive neurons, and peripherin (PRPH)-positive neurons, a marker for pain sensing neurons. In diabetic mice, N200-positive neurons were reduced by 30%. Furthermore, diabetes increased the percentage of N200-positive neurons with cytoplasmic vacuoles, a sign of damage and stress, by 2.44 fold. In addition, the average number of vacuoles was 1.6 fold higher in diabetic mice. Therapies aimed at reducing this loss could help patients better protect their limbs from injuries and thus reduce amputations.
糖尿病周围神经病变（DPN）是糖尿病最常见的并发症。一半的DPN患者会出现感觉缺陷，包括感觉丧失和疼痛。感觉丧失会增加足部受伤未被察觉的风险，再加上血液循环不良和愈合能力差，会导致截肢。2型糖尿病占足部截肢病例的50%，这凸显了感觉丧失对患者生活质量的重大影响。然而，DPN中感觉丧失的细胞基础仍不清楚。我们在2型糖尿病的db/db小鼠模型中，对背根神经节（DRG）中糖尿病诱导的神经元损失和损伤进行了表征。对32周龄糖尿病（db/db）小鼠腰段DRG中的两个神经元群体进行了形态计量学表征。这些是N200阳性神经元，它是低阈值和高阈值机械敏感感觉神经元及本体感觉神经元的标志物，以及外周蛋白（PRPH）阳性神经元，它是痛觉感受神经元的标志物。在糖尿病小鼠中，N200阳性神经元减少了30%。此外，糖尿病使有细胞质空泡的N200阳性神经元的百分比增加了2.44倍，细胞质空泡是损伤和应激的标志。此外，糖尿病小鼠的空泡平均数量高出1.6倍。旨在减少这种损失的治疗方法可以帮助患者更好地保护其肢体免受损伤，从而减少截肢。
