Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
Department of Breast and Thyroid Surgery, The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
Mol Med Rep. 2017 Aug;16(2):1739-1746. doi: 10.3892/mmr.2017.6786. Epub 2017 Jun 15.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by selective degeneration of upper and lower motor neurons. The disease progression is associated with the astrocytic environment. Aquaporin-4 (AQP4) water channels are the most abundant AQPs expressed in astrocytes, exerting important influences on central nervous system homeostasis. The present study aimed to characterize the alterations in AQP4 expression and loca-lization in superoxide dismutase 1 (SOD1) G93A transgenic mice. SOD1G93A mice were sacrificed during the presymptomatic, disease onset and end stages and immunostaining was performed on spinal cord sections to investigate neuronal loss, glial activation and AQP4 expression in the spinal cord. It was observed that global AQP4 expression increased in the spinal cord of SOD1G93A mice as the disease progressed. However, AQP4 polarization decreased as the disease progressed, and AQP4 polarized localization at the endfeet of astrocytes was decreased in the spinal ventral horn of SOD1G93A mice at the disease onset and end stages. Meanwhile, motor neuron dege-neration and decreased glutamate transporter 1 expression in astrocytes in SOD1G93A mice were observed as the disease progressed. The results of the present study demonstrated that AQP4 depolarization is a widespread pathological condition and may contribute to motor neuron degeneration in ALS.
肌萎缩侧索硬化症（ALS）是一种进行性神经退行性疾病，其特征是上下运动神经元选择性退化。疾病的进展与星形胶质细胞的环境有关。水通道蛋白 4（AQP4）水通道是星形胶质细胞中表达最丰富的 AQP，对中枢神经系统的内稳态发挥着重要影响。本研究旨在描述超氧化物歧化酶 1（SOD1）G93A 转基因小鼠中 AQP4 表达和定位的改变。在疾病的前症状期、发病期和终末期，处死 SOD1G93A 小鼠，并对脊髓切片进行免疫染色，以研究脊髓神经元丢失、神经胶质激活和 AQP4 的表达。结果发现，随着疾病的进展，SOD1G93A 小鼠脊髓中的 AQP4 整体表达增加。然而，随着疾病的进展，AQP4 的极化减少，AQP4 在星形胶质细胞终足的极化定位在 SOD1G93A 小鼠脊髓腹角在疾病发病和终末期减少。同时，随着疾病的进展，SOD1G93A 小鼠中的运动神经元退化和星形胶质细胞中谷氨酸转运蛋白 1 的表达减少。本研究的结果表明，AQP4 的去极化是一种广泛存在的病理状态，可能导致 ALS 中运动神经元的退化。
