title: Changes in the astrocytic aquaporin-4 and inwardly rectifying potassium channel expression in the brain of the amyotrophic lateral sclerosis SOD1(G93A)  rat model.
abstract: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting upper and lower motor neurons. Dysfunction and death of motor neurons are closely related to the modified astrocytic environment. Astrocytic endfeet, lining the blood-brain barrier (BBB), are enriched in two proteins, aquaporin-4 (AQP4) and inwardly rectifying potassium channel (Kir) 4.1. Both channels are important for the maintainance of a functional BBB astrocytic lining. In this study, expression levels of AQP4 and Kir4.1 were for the first time examined in the brainstem and cortex, along with the functional properties of Kir channels in cultured cortical astrocytes of the SOD1(G93A) rat model of ALS. Western blot analysis showed increased expression of AQP4 and decreased expression of Kir4.1 in the brainstem and cortex of the ALS rat. In addition, higher immunoreactivity of AQP4 and reduced immunolabeling of Kir4.1 in facial and trigeminal nuclei as well as in the motor cortex were also observed. Particularly, the observed changes in the expression of both channels were retained in cultured astrocytes. Furthermore, whole-cell patch-clamp recordings from cultured ALS cortical astrocytes showed a significantly lower Kir current density. Importantly, the potassium uptake current in ALS astrocytes was significantly reduced at all extracellular potassium concentrations. Consequently, the Kir-specific Cs(+)- and Ba(2+)-sensitive currents were also decreased. The changes in the studied channels, notably at the upper CNS level, could underline the hampered ability of astrocytes to maintain water and potassium homeostasis, thus affecting the BBB, disturbing the neuronal microenvironment, and causing motoneuronal dysfunction and death.
authors.affiliation: Center for Laser Microscopy, Faculty of Biology, University of Belgrade, Studentski trg 3, POB 52, Belgrade, Serbia.
authors.forename: Danijela
authors.initials: D
authors.lastname: Bataveljić
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Nikolić
authors.forename: Milena
authors.initials: M
authors.lastname: Milosević
authors.forename: Nataša
authors.initials: N
authors.lastname: Todorović
authors.forename: Pavle R
authors.initials: PR
authors.lastname: Andjus
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D051401:Aquaporin 4 / Q000096:biosynthesis* / Q000235:genetics; D001253:Astrocytes / Q000378:metabolism*; D001933:Brain Stem / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D000098854:Kcnj10 Channel
chemical_list: C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D000098854:Kcnj10 Channel; D024661:Potassium Channels, Inwardly Rectifying; C000606290:SOD1 protein, human; C109415:SOD1 G93A protein; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1