Human Molecular Genetics Advance Access published online on March 20, 2009
Human Molecular Genetics, doi:10.1093/hmg/ddp136
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Astrocytic protection of spinal motor neurons but not cortical neurons against loss of Als2/alsin function
1 Institut de Biologie du Développement de Marseille Luminy IBDML, Marseille, France 2 Institut Pasteur, INSERM U622, Paris, France
* corresponding author: Georg Haase, MD PhD, Laboratory of Motor Neuron Disease Modeling and Therapy Institut de Biologie du Développement de Marseille Luminy/Université Aix-Marseille, Case 907, Parc scientifique de Luminy, F-13273 Marseille cedex 09, France, E-mail: haase{at}ibdml.univ-mrs.fr, Phone: +33.4.91.26.92.78, Phone: +33.6.73.23.81.13, Fax: +33.4.91.26.97.57
Received December 3, 2008; Revised March 1, 2009; Accepted March 18, 2009
Three neurodegenerative diseases affecting upper and/or lower motor neurons have been associated with loss of ALS2/Alsin function: juvenile amyotrophic lateral sclerosis, primary lateral sclerosis and infantile-onset ascending hereditary spastic paralysis. The distinct neuronal vulnerability and the role of glia in these diseases remained however unclear. We here demonstrate that alsin-depleted spinal motor neurons can be rescued from defective survival and axon growth by co-cultured astrocytes. The astrocytic rescue is mediated by a soluble protective factor rather than by cellular contact. Cortical neurons are intrinsically as vulnerable to alsin depletion as spinal motor neurons but cannot be rescued by co-cultured astrocytes. To our knowledge these data provide the first example of non cell-autonomous glial effects in a recessive form of motor neuron disease and a potential rationale for the higher vulnerability of upper versus lower motor neurons in ALS2/Alsin-linked disorders.