Inhibition of NMDA Receptors Downregulates Astrocytic AQP4 to Suppress Seizures
- PDF / 6,347,936 Bytes
- 13 Pages / 595.276 x 790.866 pts Page_size
- 39 Downloads / 156 Views
ORIGINAL RESEARCH
Inhibition of NMDA Receptors Downregulates Astrocytic AQP4 to Suppress Seizures Shuisheng Lei1 · Yan He1 · Ziting Zhu1,2 · Zhongrui Liu1 · Yuwan Lin1,2 · Yuehua He1 · Sheng Du1 · Xiang Chen2 · Pingyi Xu1,2 · Xiaoqin Zhu1 Received: 23 July 2019 / Accepted: 14 February 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Aquaporin 4 (AQP4), a water-specific channel protein locating on the astrocyte membrane, has been found to be antagonist, agonist and undergone closely related to epilepsy. Our previous study showed that inhibition of an N-methyl-d-aspartate receptor (NMDAR) subunit NR2A can suppress epileptic seizures, suggesting that AQP4 is potentially involved in NR2A-mediated epilepsy treatment. In this study, we aimed to explore the relevance of AQP4 in NR2A-mediated seizures treatment in pentylenetetrazol (PTZ)-induced rat models. We performed electroencephalogram (EEG) recording and examined AQP4 expression at mRNA and protein levels, and the downstream molecules of AQP4 as well. It showed that AQP4 expression was increased after the induction of seizures. Lateral ventricle pretreatment of NR2A inhibitor could mitigate the PTZ-induced seizures severity and counterbalance the increase of AQP4 expression. In contrast, NR2A activator that resulted in seizures aggravation could further augment the seizure-related elevations of AQP4 expression. Pharmacological inhibition of AQP4 alone could also suppress the PTZ-induced seizure activities, with decreased expressions of NF-κB p65, interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α in the brain. The results indicated that increased expression of AQP4 might be an important mechanism involved in NR2A of NMDAR-mediated treatment for epileptic seizures, enlightening a potentially new target for seizures treatment. Keywords Seizures · NMDAR · NR2A · Aquaporin 4 · Inflammation · NF-κB.
Introduction Epilepsy, a common neurological disorder with an estimated 65 million people affected all over the world, is characterized by repeated spontaneous seizures and abnormal synchronized discharges in neurons (Devinsky et al. 2018). Seizure generation is determined by multiple factors, including N-methyl-d-aspartate receptors (NMDAR), one of the most Shuisheng Lei and Yan He have contributed equally to this work. * Pingyi Xu [email protected] * Xiaoqin Zhu [email protected] 1
Department of Physiology, Key Laboratory of Neuroscience, School of Basic Medical Sciences, Department of Dermatology, The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China
Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China
2
widely studied receptors of excitatory neurotransmitter glutamate. NMDAR plays a crucial role in the pathogenesis of seizures. The activation of NMDAR mediates neuronal hyper-excitability and excitotoxicity (Lemke et al. 2013). NMDAR non-selective antagonist MK-801 inhibits seizures activities and reduces cell damage caused b
Data Loading...
