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Open AccessArticle

CD34 Identifies a Subset of Proliferating Microglial Cells Associated with Degenerating Motor Neurons in ALS

Institut Pasteur de Montevideo, Montevideo 11400, Uruguay
Linus Pauling Institute, Department of Biochemistry and Biophysics, Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331, USA
Imagine Institute, Hôpital Necker, 75015 Paris, France
INSERM UMR 1163, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implications, 75015 Paris, France
Paris Descartes–Sorbonne Paris Cité University, Imagine Institute, 75006 Paris, France
CNRS ERL 8254, INSERM U1163, Université Paris Descartes, 75006 Paris, France
Laboratory of Excellence GR-Ex, 75015 Paris, France
Equipe Labélisée par la Ligue Nationale contre le cancer, 75013 Paris, France
AB Science, 75008 Paris, France
Department of Hematology, Hôpital Necker, 75015 Paris, France
Centre national de référence des mastocytoses (CEREMAST), 75743 Paris, France
Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Birmingham Veterans Affairs Medical Center, Birmingham, AL 35294, USA
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(16), 3880;
Received: 31 May 2019 / Revised: 9 July 2019 / Accepted: 16 July 2019 / Published: 9 August 2019
(This article belongs to the Special Issue Amyotrophic Lateral Sclerosis: Highlights of Its Complexity)
Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of upper and lower motor neurons accompanied by proliferation of reactive microglia in affected regions. However, it is unknown whether the hematopoietic marker CD34 can identify a subpopulation of proliferating microglial cells in the ALS degenerating spinal cord. Immunohistochemistry for CD34 and microglia markers was performed in lumbar spinal cords of ALS rats bearing the SOD1G93A mutation and autopsied ALS and control human subjects. Characterization of CD34-positive cells was also performed in primary cell cultures of the rat spinal cords. CD34 was expressed in a large number of cells that closely interacted with degenerating lumbar spinal cord motor neurons in symptomatic SOD1G93A rats, but not in controls. Most CD34+ cells co-expressed the myeloid marker CD11b, while only a subpopulation was stained for Iba1 or CD68. Notably, CD34+ cells actively proliferated and formed clusters adjacent to damaged motor neurons bearing misfolded SOD1. CD34+ cells were identified in the proximity of motor neurons in autopsied spinal cord from sporadic ALS subjects but not in controls. Cell culture of symptomatic SOD1G93A rat spinal cords yielded a large number of CD34+ cells exclusively in the non-adherent phase, which generated microglia after successive passaging. A yet unrecognized CD34+ cells, expressing or not the microglial marker Iba1, proliferate and accumulate adjacent to degenerating spinal motor neurons, representing an intriguing cell target for approaching ALS pathogenesis and therapeutics. View Full-Text
Keywords: microglia; CD34; amyotrophic lateral sclerosis; misfolded SOD1; motor neurons microglia; CD34; amyotrophic lateral sclerosis; misfolded SOD1; motor neurons
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Kovacs, M.; Trias, E.; Varela, V.; Ibarburu, S.; Beckman, J.S.; Moura, I.C.; Hermine, O.; King, P.H.; Si, Y.; Kwon, Y.; Barbeito, L. CD34 Identifies a Subset of Proliferating Microglial Cells Associated with Degenerating Motor Neurons in ALS. Int. J. Mol. Sci. 2019, 20, 3880.

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