ArticleHuman molecular genetics2015
Analysis of YFP(J16)-R6/2 reporter mice and postmortem brains reveals early pathology and increased vulnerability of callosal axons in Huntington's disease.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 51 citations in OpenAlex.
- In Vivo Mapping of Catecholaminergic Loss and Iron Deposition in Huntington's Disease.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Environmental Deprivation Effects on Myelin Ultrastructure in Huntington Disease and Wildtype Mice.Molecular neurobiology · 2024Article
- Toxic effects of mutant huntingtin in axons are mediated by its proline-rich domain.Brain : a journal of neurology · 2024Article
- The contribution of preclinical magnetic resonance imaging and spectroscopy to Huntington's disease.Frontiers in aging neuroscience · 2024Review
- Disruption of axonal transport in neurodegeneration.The Journal of clinical investigation · 2023Review
- M2 Cortex Circuitry and Sensory-Induced Behavioral Alterations in Huntington's Disease: Role of Superior Colliculus.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Treatment with the Glycosphingolipid Modulator THI Rescues Myelin Integrity in the Striatum of R6/2 HD Mice.International journal of molecular sciences · 2023Article
- A Transgenic 5xFAD-M Line of Mice for Dendritic Spine Morphology Analysis in Alzheimer's Disease.Brain sciences · 2023Article
- Review
- Pathophysiology of neurodegenerative diseases: An interplay among axonal transport failure, oxidative stress, and inflammation?Seminars in immunology · 2022Review
- Fixel-Based Analysis Effectively Identifies White Matter Tract Degeneration in Huntington's Disease.Frontiers in neuroscience · 2021Article
- Neurofilament Light Chain and Intermediate HTT Alleles as Combined Biomarkers in Italian ALS Patients.Frontiers in neuroscience · 2021Article
- The human motor cortex microcircuit: insights for neurodegenerative disease.Nature reviews. Neuroscience · 2020Review
- Assessing neuraxial microstructural changes in a transgenic mouse model of early stage Amyotrophic Lateral Sclerosis by ultra-high field MRI and diffusion tensor metrics.Animal models and experimental medicine · 2020Article
- EGF Treatment Improves Motor Behavior and Cortical GABAergic Function in the R6/2 Mouse Model of Huntington's Disease.Molecular neurobiology · 2019Article
- Detection of axonal degeneration in a mouse model of Huntington's disease: comparison between diffusion tensor imaging and anomalous diffusion metrics.Magma (New York, N.Y.) · 2019Article
- Early Downregulation of p75Molecular neurobiology · 2019Article
- Diffusion tensor imaging as a tool to detect presymptomatic axonal degeneration in a preclinical spinal cord model of amyotrophic lateral sclerosis.Neural regeneration research · 2018Article
- Molecular insights into cortico-striatal miscommunications in Huntington's disease.Current opinion in neurobiology · 2018Review
- Ultra-High Field Diffusion MRI Reveals Early Axonal Pathology in Spinal Cord of ALS mice.Translational neurodegeneration · 2018Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Cumulative evidence indicates that the onset and severity of Huntington's disease (HD) symptoms correlate with connectivity deficits involving specific neuronal populations within cortical and basal ganglia circuits. Brain imaging studies and pathological reports further associated these deficits with alterations in cerebral white matter structure and axonal pathology. However, whether axonopathy represents an early pathogenic event or an epiphenomenon in HD remains unknown, nor is clear the identity of specific neuronal populations affected. To directly evaluate early axonal abnormalities in the context of HD in vivo, we bred transgenic YFP(J16) with R6/2 mice, a widely used HD model. Diffusion tensor imaging and fluorescence microscopy studies revealed a marked degeneration of callosal axons long before the onset of motor symptoms. Accordingly, a significant fraction of YFP-positive cortical neurons in YFP(J16) mice cortex were identified as callosal projection neurons. Callosal axon pathology progressively worsened with age and was influenced by polyglutamine tract length in mutant huntingtin (mhtt). Degenerating axons were dissociated from microscopically visible mhtt aggregates and did not result from loss of cortical neurons. Interestingly, other axonal populations were mildly or not affected, suggesting differential vulnerability to mhtt toxicity. Validating these results, increased vulnerability of callosal axons was documented in the brains of HD patients. Observations here provide a structural basis for the alterations in cerebral white matter structure widely reported in HD patients. Collectively, our data demonstrate a dying-back pattern of degeneration for cortical projection neurons affected in HD, suggesting that axons represent an early and potentially critical target for mhtt toxicity.
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