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In ALS patients and rodent models, EAAT2 expression is reduced in astrocytes in the motor cortex and spinal cord, which could cause an accumulation of excitotoxic levels of extracellular glutamate and subsequently increase the neuronal intracellular calcium concentration and initiate cascades that regulate motor neuron death ([99103]

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These findings were further corroborated within the Lifelines Cohort, where results showed sex- and duration-specific DNA methylation changes in women exposed to intermediate-term NSW (10-16 years), enriched in pathways related to circadian regulation and cellular senescence