Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease characterized by the death of upper and lower motor neurons (MN) in the central nervous system (CNS). While mutations associated with ALS are known to result in the degeneration of MNs, less is understood about their effects on non-neuronal cells such as astrocytes. Astrocytes play a key role in neuroinflammation which is a hallmark and driver of neurodegenerative disease. How mutations affect the reactivity and ability of astrocytes to respond to stress or damage in the CNS remains unknown. This work aims to identify the effects of the familial ALS-associated mutations SOD1 A4V and C9orf72 hexanucleotide expansion repeat on astrocyte activation to provide insight into the role these mutations have in ALS pathogenesis. Human-derived induced pluripotent stems cells from ALS patients with mutations of interest were used to generate mutant astrocytes for in vitro experiments. Astrocytes were activated with inflammatory cytokines, and their responding gene expression was evaluated via Real-Time quantitative PCR (RT-qPCR). Comparisons between morphological and RT-qPCR results from astrocytes cultured in serum-free and fetal bovine serum (FBS), a common astrocyte media supplement, revealed that FBS had unexpected long-term dampening effects on astrocyte activation. The findings suggest that culturing astrocytes in FBS may be a potential model for simulating chronic low-grade inflammation, as is typically observed in ALS. Our findings show that chronically inflamed SOD1 A4V mutant astrocytes have an overreactive response to inflammatory cytokines, which may contribute to MN death and ALS pathogenesis.
"},{"label":"Degree","value":["Bachelor of Arts with Departmental Honors"]},{"label":"Author-supplied Keywords","value":["ALS","Inflammation","Astrocytes"]},{"label":"Administrative Note","value":"Drupal Node ID: 33904