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The Journal of Neuroscience, October 8, 2008, 28(41):10234-10244; doi:10.1523/JNEUROSCI.3494-08.2008

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Neurobiology of Disease
Ablation of Proliferating Microglia Does Not Affect Motor Neuron Degeneration in Amyotrophic Lateral Sclerosis Caused by Mutant Superoxide Dismutase

Genevíève Gowing,^1,2 * Thomas Philips,^3,4,5 * Bart Van Wijmeersch,⁶ Jean-Nicolas Audet,^1,2 Maarten Dewil,^3,4 Ludo Van Den Bosch,^3,4,5 An D. Billiau,⁶ Wim Robberecht,^3,4,5 and Jean-Pierre Julien^1,2

¹Laboratory of Molecular Endocrinology, Centre de Recherche du Centre Hospitalier de l'Université Laval and ²Department of Anatomy and Physiology, Laval University, Québec City, Québec, Canada G1V 4G2, ³Vesalius Research Institute, Flanders Institute for Biotechnology, 9052 Gent, Belgium, and Laboratories for ⁴Neurobiology, ⁵Experimental Neurology, and ⁶Experimental Transplantation, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium

Correspondence should be addressed to Jean-Pierre Julien, Bloc T2, Centre de Recherche du Centre Hospitalier de l'Université Laval, 2705 Boulevard Laurier, Québec City, Québec, Canada G1V 4G2. Email: jean-pierre.julien{at}crchul.ulaval.ca

Microglial activation is a hallmark of all neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Here, a detailed characterization of the microglial cell population within the spinal cord of a mouse model of familial ALS was performed. Using flow cytometry, we detected three distinct microglial populations within the spinal cord of mice overexpressing mutant superoxide dismutase (SOD1): mature microglial cells (CD11b⁺, CD45^low), myeloid precursor cells (CD11b⁺, CD45^int), and macrophages (CD11b⁺, CD45^high). Characterization of cell proliferation within the CNS of SOD1^G93A mice revealed that the expansion in microglial cell population is mainly attributable to the proliferation of myeloid precursor cells. To assess the contribution of proliferating microglia in motor neuron degeneration, we generated CD11b-TK^mut-30; SOD1^G93A doubly transgenic mice that allow the elimination of proliferating microglia on administration of ganciclovir. Surprisingly, a 50% reduction in reactive microglia specifically in the lumbar spinal cord of CD11b-TK^mut-30; SOD1^G93A doubly transgenic mice had no effect on motor neuron degeneration. This suggests that proliferating microglia-expressing mutant SOD1 are not central contributors of the neurodegenerative process in ALS caused by mutant SOD1.

Key words: ALS; microglia; motor neuron; degeneration; ablation; transgenic mice

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Received July 24, 2008; accepted Aug. 28, 2008.

Correspondence should be addressed to Jean-Pierre Julien, Bloc T2, Centre de Recherche du Centre Hospitalier de l'Université Laval, 2705 Boulevard Laurier, Québec City, Québec, Canada G1V 4G2. Email: jean-pierre.julien{at}crchul.ulaval.ca

This article has been cited by other articles:

				Y. Liu, W. Hao, A. Dawson, S. Liu, and K. Fassbender Expression of Amyotrophic Lateral Sclerosis-linked SOD1 Mutant Increases the Neurotoxic Potential of Microglia via TLR2 J. Biol. Chem., February 6, 2009; 284(6): 3691 - 3699. [Abstract] [Full Text] [PDF]

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