title: Astrocytic protection of spinal motor neurons but not cortical neurons against loss of Als2/alsin function.
abstract: 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 remains, 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.
authors.affiliation: 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.
authors.forename: A
authors.initials: A
authors.lastname: Jacquier
authors.forename: S
authors.initials: S
authors.lastname: Bellouze
authors.forename: S
authors.initials: S
authors.lastname: Blanchard
authors.forename: D
authors.initials: D
authors.lastname: Bohl
authors.forename: G
authors.initials: G
authors.lastname: Haase
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D016472:Motor Neuron Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009046:Motor Neurons / Q000378:metabolism*; D013131:Spine / Q000166:cytology* / Q000378:metabolism / Q000503:physiopathology
chemical_list: C512358:Als2 protein, mouse; D020662:Guanine Nucleotide Exchange Factors