Original Research ARTICLE

Front. Cell. Neurosci., 24 December 2013 | doi: 10.3389/fncel.2013.00274

Phenotypic transition of microglia into astrocyte-like cells associated with disease onset in a model of inherited ALS

Emiliano Trias1, Pablo Díaz-Amarilla1, Silvia Olivera-Bravo1, Eugenia Isasi1, Derek A. Drechsel2,3, Nathan Lopez2,3, C. Samuel Bradford2,3, Kyle E. Ireton2,3,5, Joseph S. Beckman2,3,4 and Luis Barbeito5*
  • 1Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay
  • 2Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR, USA
  • 3Environmental Health Sciences Center, Oregon State University, Corvallis, OR, USA
  • 4Linus Pauling Institute, Oregon State University, Corvallis, OR, USA
  • 5Institut Pasteur de Montevideo, Montevideo, Uruguay

Microglia and reactive astrocytes accumulate in the spinal cord of rats expressing the Amyotrophic lateral sclerosis (ALS)-linked SOD1G93A mutation. We previously reported that the rapid progression of paralysis in ALS rats is associated with the appearance of proliferative astrocyte-like cells that surround motor neurons. These cells, designated as Aberrant Astrocytes (AbA cells) because of their atypical astrocytic phenotype, exhibit high toxicity to motor neurons. However, the cellular origin of AbA cells remains unknown. Because AbA cells are labeled with the proliferation marker Ki67, we analyzed the phenotypic makers of proliferating glial cells that surround motor neurons by immunohistochemistry. The number of Ki67+AbA cells sharply increased in symptomatic rats, displaying large cell bodies with processes embracing motor neurons. Most were co-labeled with astrocytic marker GFAP concurrently with the microglial markers Iba1 and CD163. Cultures of spinal cord prepared from symptomatic SOD1G93A rats yielded large numbers of microglia expressing Iba1, CD11b, and CD68. Cells sorted for CD11b expression by flow cytometry transformed into AbA cells within two weeks. During these two weeks, the expression of microglial markers largely disappeared, while GFAP and S100β expression increased. The phenotypic transition to AbA cells was stimulated by forskolin. These findings provide evidence for a subpopulation of proliferating microglial cells in SOD1G93A rats that undergo a phenotypic transition into AbA cells after onset of paralysis that may promote the fulminant disease progression. These cells could be a therapeutic target for slowing paralysis progression in ALS.

Keywords: microglia, astrocytes, AbA cells, ALS, phenotypic transformation, neurodegeneration

Citation: Trias E, Díaz-Amarilla P, Olivera-Bravo S, Isasi E, Drechsel DA, Lopez N, Bradford CS, Ireton KE, Beckman JS and Barbeito L (2013) Phenotypic transition of microglia into astrocyte-like cells associated with disease onset in a model of inherited ALS. Front. Cell. Neurosci. 7:274. doi: 10.3389/fncel.2013.00274

Received: 18 July 2013; Paper pending published: 05 November 2013;
Accepted: 09 December 2013; Published online: 24 December 2013.

Edited by:

Ricardo Tapia, Universidad Nacional Autónoma de México, Mexico

Reviewed by:

Ricardo Tapia, Universidad Nacional Autónoma de México, Mexico
Jie Zhang, University of Texas Health Science Center at San Antonio, USA

Copyright © 2013 Trias, Díaz-Amarilla, Olivera-Bravo, Isasi, Drechsel, Lopez, Bradford, Ireton, Beckman and Barbeito. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Luis Barbeito, Institut Pasteur de Montevideo, Mataojo 2020, Montevideo 11400, Uruguay e-mail: barbeito@pasteur.edu.uy

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