Jacquier A, Bellouze S, Blanchard S, Bohl D, Haase G
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.
Hum Mol Genet. 2009 Jun 15;18(12):2127-39. doi: 10.1093/hmg/ddp136. Epub 2009 Mar 20.
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.
三种影响上运动神经元和/或下运动神经元的神经退行性疾病与ALS2/阿尔辛功能丧失有关：青少年肌萎缩侧索硬化症、原发性侧索硬化症和婴儿期起病的上行性遗传性痉挛性截瘫。然而，这些疾病中不同的神经元易损性以及胶质细胞的作用仍不清楚。我们在此证明，通过与星形胶质细胞共培养，可挽救缺乏阿尔辛的脊髓运动神经元的生存缺陷和轴突生长缺陷。星形胶质细胞的挽救作用是由一种可溶性保护因子介导的，而不是通过细胞接触。皮质神经元本质上与脊髓运动神经元一样易受阿尔辛缺失的影响，但不能通过与星形胶质细胞共培养来挽救。据我们所知，这些数据提供了运动神经元疾病隐性形式中非细胞自主性胶质细胞效应的首个例子，以及ALS2/阿尔辛相关疾病中上运动神经元比下运动神经元更易受损的潜在原因。
