Dataset Information

Cerebrospinal fluid from HAM/TSP patients with rapid evolution affects mitochondrial DNA transcription and structure in human glioblastoma cell lines

ABSTRACT: Human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive neurodegenerative disease impacting motor and sensorial functions. While the cerebrospinal fluid (CSF) alterations have been used to identify biomarkers for this disease, the effects of HTLV-1 CSF on neural cells remain unexplored. Herein, we investigated the impact of CSF from HTLV-1 infected patients on glioblastoma cell lines. CSF samples were obtained from HTLV-1 asymptomatic carriers (HAC) (n=13), and HAM/TSP patients (n=21) categorized according to the speed of disease progression: very slow (HAMvs), typical (HAMt), and rapid (HAMr). RNA sequencing of glioblastoma cells treated with HTLV-1 CSF revealed notable gene expression changes, particularly with HAMr CSF, which caused significant downregulation of mitochondrial DNA transcripts. Confocal microscopy showed phenotypical changes in the mitochondrial network: astrocytes exposed to HAMr CSF exhibited a less complex mitochondrial network compared to CSF from other patient groups. It is characterized by reduced mitochondrial branching, fewer junctions per branch length, and slightly increased branch diameter. Compared to untreated cells, HTLV+ CSF disturbed mitochondrial metabolism. However, these changes are limited at the metabolic level and do not appear to vary significantly with HTLV donor status. In conclusion, our findings suggest that HTLV+ CSF induces mitochondrial reorganization in glioblastoma cells, potentially helping to compensate for the stress caused by the CSF exposure.

ORGANISM(S): Homo sapiens

PROVIDER: GSE290808 | GEO | 2025/04/15

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an inflammatory neurodegenerative disease that affects motor, urinary, intestinal, and sensory functions. Typically, HAM/TSP is slowly progressive, but it may vary from limited motor disability after decades (very slow progression) to loss of motor function in a few years from disease onset (rapid). In this study, we aimed to identify prognostic biomarkers for HAM/TSP to support patient management. Thus, proteomic analysis of the cerebrospinal fluid (CSF) was performed with samples from HTLV-1 asymptomatic carriers (AC) (n=13) and HAM/TSP patients (n=21) with rapid, typical, and very slow progression using quantitative label-free liquid chromatography/tandem mass spectrometry. Enrichment analyses were also carried out to identify key biological processes associated with distinct neurological conditions in HTLV-1 infection. Candidate biomarkers were validated by ELISA in paired CSF and serum samples, and samples from HTLV-1-seronegative individuals (n=9) were used as controls. CSF analysis identified 602 proteins. Leukocyte/cell activation, immune response processes and neurodegeneration pathways were enriched in rapid progressors. Conversely, HTLV-1 AC and HAM/TSP patients with typical and very slow progression had enriched processes for nervous system development. Differential expression analysis showed that soluble vascular cell adhesion molecule 1 (sVCAM-1), chitotriosidase 1 (CHIT1), and cathepsin C (CTSC) were upregulated in HAM/TSP. However, only CHIT1 was significantly elevated after validation, particularly in HAM/TSP rapid progressors. In contrast, none of these biomarkers were altered in serum. Additionally, CSF CHIT1 levels in HAM/TSP patients positively correlated with the speed of HAM/TSP progression, defined as points in the IPEC-2 HAM/TSP disability scale per year of disease, and with CSF levels of phosphorylated neurofilament heavy chain, neopterin, CXCL5, CXCL10, and CXCL11. In conclusion, higher CSF levels of CHIT1 were associated with HAM/TSP rapid progression and correlated with other biomarkers of neuroinflammation and neurodegeneration. Therefore, we propose CHIT1 as a surrogate CSF biomarker to identify HAM/TSP patients with a worse prognosis.

Dataset Information

Cerebrospinal fluid from HAM/TSP patients with rapid evolution affects mitochondrial DNA transcription and structure in human glioblastoma cell lines

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets