Decreased Expression of Alpha1 Subunit of Na(+)/K+-Atpase in the Als Rat Brain

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting predominantly motoneurons but with a particular pathological role of non-neuronal cells. Previous research suggested that increased concentration of extracellular potassium could lead to motoneuron dysfunction. The Na /K -ATPase should regulate the homeostasis of potassium ions and thus help maintain regular neuronal activity. This homeostasis m. he regulated by Nat/K'-ATPase in both neurons and astrocytes. In ordere to reveal the possible role of the Na'/K -ATPase in ALS pathology, we explared the expression of the alphal catalytic subunit of Na/K-ATPase in neurons and astrocytes from different brain regions of the SOD19934 rat model of ALS. Labeling immunofluorescently the alphal isoform of the Na' /K'-ATPase revealed a decreased signal in the trigemi-1 nal nucleus and cerebellum of the ALS rat. Double immunofluorecence with NeuN for neurons showed that the reduced alphal was on the neuronal surface in the trigeminal nucleus. In addition, the alphal ring-like staining of cerebellar granule neurons was lower in ALS as compared to the wild type rat. In comparison to neurons, astrocytes from the wild type rat were characterized with a lower expression of alphal. In the examined brain regions we did not observe a prominent difference in alphal expression between astrocytes of wild Lype and ALS rats. Based on the findings of this study the prominent reduction of Nat/K'-ATPase level observed in neurons and not in astrocytes could contribute to further understaning of impaired ion homeostasis affecting proper neuronal physiology in ALS. The role of glial Na/K*-ATPase needs to be further studied with markers of other alpha subunit isoforms.