ArticleActa neuropathologica communications2021
Microglial transcriptome analysis in the rNLS8 mouse model of TDP-43 proteinopathy reveals discrete expression profiles associated with neurodegenerative progression and recovery.
Article in Acta neuropathologica communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Evaluation of triumeq treatment on a TDP-43 mouse model of amyotrophic Lateral sclerosis.Scientific reports · 2026Article
- Genetic suppression of myeloid receptor Clec7a attenuates microglia neuroinflammation and promotes microglial phagocytosis to delay disease progression in ALS models.bioRxiv : the preprint server for biology · 2026Article
- Regional Molecular Diversity in Chronic Spinal Cord Injury.Cellular and molecular neurobiology · 2026Article
- Sustained Transcriptional Response to Lipopolysaccharide and Interleukin-4 in an Immortalized Mouse Microglial Cell Line.Molecular neurobiology · 2026Article
- Cognitive dysfunction in type 1 diabetes: role of TREM2 in microglial activation and Aβ pathology.Journal of neuroinflammation · 2026Article
- Cystatin F as a neuroimmune effector in CNS inflammation and neurodegeneration.Frontiers in cell and developmental biology · 2026Review
- Increased CSF levels of soluble AXL at diagnosis correlate with poor prognosis in patients affected by amyotrophic lateral sclerosis.Brain communications · 2026Article
- Synaptic changes contribute to persistent extra-motor behaviour deficits in amyotrophic lateral sclerosis.Acta neuropathologica communications · 2025Article
- Neuronal TDP-43 pathology drives astrocytic interferon response in a mouse model of ALS.Journal of neuroinflammation · 2025Article
- Integrated multi-omics profiling uncovers miRNA-guided regulatory networks after spinal cord injury in rats.Molecular therapy. Nucleic acids · 2025Article
- Differential effects of overexpression of mutant huntingtin and TDP-43 in agouti-related protein neurons in the arcuate nucleus of the hypothalamus in mice.Acta neuropathologica communications · 2025Article
- Cystatin F-a key player in central nervous system disease.Journal of neuroinflammation · 2025Review
- Uncovering the Associations of LILRB4 Genotypes With Parkinson's Disease: From Clinical Traits to Potential Pathologies.CNS neuroscience & therapeutics · 2025Article
- Unlocking Disease-Modifying Treatments for TDP-43-Mediated Neurodegeneration.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Neuronal TDP-43 aggregation drives changes in microglial morphology prior to immunophenotype in amyotrophic lateral sclerosis.Acta neuropathologica communications · 2025Article
- Article
- Alternative 3' UTR polyadenylation is disrupted in the rNLS8 mouse model of ALS/FTLD.Molecular brain · 2025Article
- Machine learning identified novel players in lipid metabolism, endosomal trafficking, and iron metabolism of the ALS spinal cord.Scientific reports · 2025Article
- Deciphering motor dysfunction and microglial activation in mThy1-Frontiers in molecular neuroscience · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
Abstract
The microglial reaction is a hallmark of neurodegenerative conditions, and elements thereof may exert differential effects on disease progression, either worsening or ameliorating severity. In amyotrophic lateral sclerosis (ALS), a syndrome characterized by cytoplasmic aggregation of TDP-43 protein and atrophy of motor neurons in the cortex and spinal cord, the transcriptomic signatures of microglia during disease progression are incompletely understood. Here, we performed longitudinal RNAseq analysis of cortical and spinal cord microglia from rNLS8 mice, in which doxycycline-regulatable expression of human TDP-43 (hTDP-43) in the cytoplasm of neurons recapitulates many features of ALS. Transgene suppression in rNLS8 mice leads to functional, anatomical and electrophysiological resolution that is dependent on a microglial reaction that is concurrent with recovery rather than disease onset. We identified basal differences between the gene expression profiles of microglia dependent on localization in spinal cord or cortex. Microglia subjected to chronic hTDP-43 overexpression demonstrated transcriptomic changes in both locations. We noted strong upregulation of Apoe, Axl, Cd63, Clec7a, Csf1, Cst7, Igf1, Itgax, Lgals3, Lilrb4, Lpl and Spp1 during late disease and recovery. Importantly, we identified a distinct suite of differentially expressed genes associated with each phase of disease progression and recovery. Differentially expressed genes were associated with chemotaxis, phagocytosis, inflammation, and production of neuroprotective factors. These data provide new insights into the microglial reaction in TDP-43 proteinopathy. Genes differentially expressed during progression and recovery may provide insight into a unique instance in which the microglial reaction promotes functional recovery after neuronal insult.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.