@conference{
author = "Perić, Mina and Nikolić, Ljiljana and Bataveljić, Danijela and Andjus, Pavle",
year = "2022",
abstract = "Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by death of motor neurons in the spinal cord and brain. Non-neuronal cells particularly of glial origin play an essential role in disease onset and progression. The aim of our study was to examine functional properties of two glial species of the spinal cord, oligodendrocytes and microglia in the ALS SOD1G93A rat with a particular focus on the expression and functional significance of the inwardly rectifying potassium channel Kir4.1 that is abundantly expressed in these glial cells.
We demonstrate that the expression of Kir4.1 is markedly diminished in oligodendrocytes of the SOD1G93A rat. Moreover, our data show an elevated number of dysmorphic oligodendrocytes, indicative of a degenerative phenotype. To assess physiological properties of oligodendrocytes, we prepared cell cultures from the rat spinal cord. The cells isolated from the SOD1G93A spinal cord displayed similar processes ramification as the control, but expressed a lower level of Kir4.1. Whole-cell patch-clamp recordings revealed compromised membrane biophysical properties and diminished inward currents in ALS oligodendrocytes, while the Ba2+-sensitive Kir current was decreased in ALS oligodendrocytes [1].
The microglia in the ALS rat spinal chords shows remarkable clustering in ventral horns, already starting in presymptomatic animals. Colocalization of Kir4.1 and microglial Iba1 staining was 2-3 times more abudant in presymptomatic as well as in symptomatic animals compared to individual cells. The morphology of micorglia also changes in ALS where the number and length of processes dicreases almost the same in pre- and symptomatic animals. It was also shown that these clusters bare a higher accumulation and colocalization with Kir4.1 and Iba1 of mutated SOD1 compared to individual cells. Similarly, the transmembrane marker of microglial fagocitosis, CD68 was also augmented in these clusters.
The spinal chord micorglial cells were cultured and explored with patch-clamp electrophysiology by using an innovative movable microscope stage [2] to facilitate the gigaseal formation of the cell membrane and patch pipette. These measurements demonstrated a decrease of Kir Ba2+-sensitive currents.
Altogether, our findings provide the evidence of impaired Kir4.1 expression and function in SOD1G93A spinal cord oligodendrocytes and microglia with this channel’s particular abundance in clusters typical of ALS pathology and its progression.
REFERENCES
[1] M.Peric, L. Nikolic L, et al. Eur J Neurosci. 54 (2021), 6339-6354.
[2] M.Peric, D. Bataveljić et al. Microsc Res Tech. (2022) , DOI: 10.1002/jemt.24066",
publisher = "Belgrade: Institute of Physics",
journal = "Book of Abstracts: 15th Photonics Workshop: Conference; 2022 Mar 13-16; Kopaonik, Serbia",
title = "Imaging the molecular markers of neurodegeneration in the ALS rat oligodendrocytes and microglia",
pages = "35",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5511"
}