ALS and Astrocytes – A Potassium Problem

Multiple approaches to multiplexing

Astrocytes often get overlooked in discussions on amyotrophic lateral sclerosis (ALS). But they’re more involved than you’d think, especially when it comes to keeping things balanced in the nervous system. In a recent study (1), researchers used SOD1 (G93A) mice, which mimic ALS pathology, crossed with a transgenic line that expresses GFP in astrocytes (thanks to the GFAP promoter). This approach allowed them to visualize astrocytes specifically and examine how ALS-like conditions affect them in different regions of the nervous system.

The study focused on Kir4.1 potassium channels, essential regulators of potassium levels around neurons. The researchers discovered that in the spinal cords of SOD1 mice – a model of ALS – Kir4.1 expression was significantly downregulated, yet the brain cortex didn’t seem to suffer the same way. This selective downregulation is bad news for motor neurons because astrocytes can’t clear excess potassium effectively without Kir4.1. The result is that spinal cord astrocytes in the ALS model have a reduced capacity to handle elevated potassium concentrations – and this leads to a toxic environment for motor neurons.

To reach these conclusions the team used a dual-labeling technique that combined GFP fluorescence, to look at astrocyte-specific changes, alongside our Guinea pig Anti-Kir4.1 (KCNJ10) Antibody (#APC-035-GP) to pinpoint Kir4.1 expression (Figure 1). This multiplex labeling allowed them to see the reduction of Kir4.1 specifically in spinal cord astrocytes. By demonstrating how ALS-like conditions selectively impair potassium homeostasis in the spinal cord, this work has uncovered a potential mechanism contributing to motor neuron degeneration.

Figure 1. Immunohistochemical analysis of Kir4.1 expression. A representative picture of Kir4.1 staining in the motor cortex. Image and legend from Filipi et al (2024) (1).

If you’d like to make use the power of multiplexing to answer more questions, you can find a host of useful reagents – like conjugated primary antibodies and antibodies raised in less common species like guinea pig – on the Multiplexing Immunodetection page. 

Alomone Labs product mentioned in this blog:

Reference

1.      T. Filipi, J. Tureckova, O. Vanatko, M. Chmelova, M. Kubiskova, N. Sirotova, S. Matejkova, L. Vargova, M. Anderova, ALS-like pathology diminishes swelling of spinal astrocytes in the SOD1 animal model. Front Cell Neurosci, 18:1472374 (2024). doi: 10.3389/fncel.2024.1472374.