Cerebrospinal Fluid From Patients With HTLV‐1‐associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) With Rapid Evolution Affects Mitochondrial DNA Transcription and Network Organization in Human Glioblastoma Cells

Human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive neurodegenerative disease affecting motor and sensory functions. While alterations in cerebrospinal fluid (CSF) have been used to identify disease biomarkers, the effects of such modified CSF on CNS cells remain unexplored. This study compared the effects of pools of CSF from HTLV-1 asymptomatic carriers (HAC) and HAM/TSP patients-categorized by disease progression as: very slow (HAMvs), typical (HAMt), and rapid (HAMr)-on the glioblastoma cell line U87-MG, a cellular model often used to study neurodegenerative diseases. RNA sequencing of U87-MG cells treated with a pool of CSFs from HAMr patients revealed a significant downregulation of transcription of mitochondrial genes after 24 h of treatment. Confocal microscopy showed phenotypical changes in the mitochondrial network: glioblastoma cells exposed to pooled HAMr CSF exhibited a less complex network compared to other patient groups. Despite these changes, U87-MG cells treated with CSF from HTLV-1-infected donors with distinct neurological outcomes presented similar mitochondrial oxygen consumption. In conclusion, these findings show that pooled HAMr CSF induces mitochondrial stress in glioblastoma cells, suggesting that CSF alterations may participate in rapidly progressing HAM/TSP pathogenesis.