AbA cells: An aberrant astrocyte population in the degenerating SOD1G93A rat spinal cord mediating motor neuron death.

PABLO DIAZ-AMARILLA; SILVIA OLIVERA-BRAVO; CRAGNOLINI, ANDREA BEATRIZ; SILVIA OLIVERA-BRAVO; PATRICIA CASSINA; LUIS BARBEITO

Congreso; Society for Neuroscience Meeting; 2010

Neurodegeneration in amyotrophic lateral sclerosis (ALS) is associated with activation and proliferation of glial cells surrounding damaged motor neurons. Astrocytes expressing ALS-linked SOD1 mutations specifically induce motor neurons loss and contribute to disease progression by yet unknown means. We report the isolation of a population of neurotoxic astrocytes from the spinal cord of symptomatic transgenic rats expressing the SOD1G93A mutation, a model of familial ALS. These cells were maintained in culture during several passages without undergoing replicative senescence. We referred to these cells as AbA cells (Aberrant Astrocytes). Aba cells displayed markers of glial cells including NG2, A2B5, GFAP, S100beta and Connexin 43, but lacked the GLT1 glutamate transporter and Olig 2. Remarkably, AbA cells exhibited a 100-fold increased toxic activity to motor neurons in the conditioned medium as compared to primary neonatal SOD1G93A astrocytes. AbA-like cells were identified in the degenerating spinal cord as displaying distinctive GFAP/S100b+ and Cx43/S100b+ immunoreactivity, in close contact with motor neurons. The emergence of aberrant astrocytes after disease onset may explain key aspects of ALS pathogenesis and defines a new diagnostic and therapeutic target for neurodegenerative diseases.