Alterations in AQP4 expression and polarization in the course of motor neuron degeneration in SOD1G93A mice

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 localization 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 degeneration 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.