MyelTracer: A Semi-Automated Software for Myelin<i>g</i>-Ratio Quantification

Kaiser, Tobias; Allen, Harrison Mitchell; Kwon, Ohyoon; Barak, Boaz; Wang, Jing; He, Zhigang; Jiang, Minqing; Feng, Guoping

doi:10.1523/eneuro.0558-20.2021

Cited by 56 publications

(44 citation statements)

References 28 publications

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“…(H-J) Analysis of TEM images revealed an increase in g-ratio in Q84/Q84 mice, but no changes in axon caliber. Axon caliber and g-ratio were calculated using MyelTracer software 25 (n=950 ± 150 axons per mouse, n=3 mice per genotype). Data reported as mean ± SEM.…”

Section: Discussionmentioning

confidence: 99%

“…Ultra-thin sections were imaged on a JEOL JEM-1400 plus transmission electron microscope (JEOL USA Inc., Peabody, MA) at an accelerating voltage of 60 kV, using either an AMT 4-megapixel XR401 or a 12-megapixel Nanosprint CMOS camera (Advanced Microscopy Techniques, Woburn, MA). For g-ratio, axon caliber, and cumulative fraction analysis of myelinated axons, MyelTracer software was used 25 .…”

Section: Transmission Electron Microscopymentioning

confidence: 99%

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Impaired oligodendrocyte maturation is an early feature in SCA3 disease pathogenesis

Schuster

Zalon

Zhang

et al. 2021

Preprint

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Spinocerebellar ataxia type 3 (SCA3), the most common dominantly inherited ataxia, is a polyglutamine neurodegenerative disease for which there is no disease-modifying therapy. The polyglutamine-encoding CAG repeat expansion in the ATXN3 gene results in expression of a mutant form of the ATXN3 protein, a deubiquitinase that causes selective neurodegeneration despite being widely expressed. The mechanisms driving neurodegeneration in SCA3 are unclear. Research to date, however, has focused almost exclusively on neurons. Here, using equal male and female age-matched transgenic mice expressing full-length human mutant ATXN3, we identified early and robust transcriptional changes in selectively vulnerable brain regions that implicate oligodendrocytes in disease pathogenesis. We mapped transcriptional changes across early, mid, and late stages of disease in two selectively vulnerable brain regions, the cerebellum and brainstem. The most significant disease-associated module through weighted gene co-expression network analysis revealed dysfunction in SCA3 oligodendrocyte maturation. These results reflect a toxic gain of function mechanism, as ATXN3 knockout mice do not exhibit any impairments in oligodendrocyte maturation. Genetic crosses to reporter mice revealed a marked reduction in mature oligodendrocytes in SCA3-disease vulnerable brain regions and ultrastructural microscopy confirmed abnormalities in axonal myelination. Further study of isolated oligodendrocyte precursor cells from SCA3 mice established that this impairment in oligodendrocyte maturation is a cell autonomous process. We conclude that SCA3 is not simply a disease of neurons and the search for therapeutic strategies and disease biomarkers will need to account for non-neuronal involvement in SCA3 pathogenesis.SIGNIFICANCE STATEMENTDespite advances in SCA3 disease understanding, much remains unknown about how the disease gene causes brain dysfunction ultimately leading to cell death. We completed a longitudinal transcriptomic analysis of vulnerable brain regions in SCA3 mice to define the earliest and most robust changes across disease progression. Through gene network analyses followed up with biochemical and histological studies in SCA3 mice, we provide evidence for severe dysfunction in oligodendrocyte maturation early in SCA3 pathogenesis. Our results advance understanding of SCA3 disease mechanisms, identify additional routes for therapeutic intervention, and may provide broader insight into polyglutamine diseases beyond SCA3.

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Section: Discussionmentioning

confidence: 99%

Section: Transmission Electron Microscopymentioning

confidence: 99%

Impaired oligodendrocyte maturation is an early feature in SCA3 disease pathogenesis

Schuster

Zalon

Zhang

et al. 2021

Preprint

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“…Only a few intuitive parameters need to be set, such as the similarity threshold or the maximum and minimum volume of a segmented component. gACSON provides several methods for semantic segmentation of myelin that are Axon instance segmentation makes no assumptions about the shape of an axon, unlike axon and myelin segmentation tools such as AxonSeg [14] or MyelTracer [16]. AxonSeg and MyelTracer work on 2D-EM data with a tissue section perpendicular to the main axonal orientation, so that the cross sections of the axons are approximately circular.…”

Section: Discussionmentioning

confidence: 99%

“…MyelTracer [16] Python-based; 2D semi-automated segmentation of axons and myelin (intensity thresholding and user's drawn lines to generate contours for myelin segmentation).…”

Section: Knossos [11]mentioning

confidence: 99%

“…There are several software tools for analyzing 3D-EM data, including open source software packages such as Microscopy Image Browser (MIB) [8], Deep-MIB [9], TrackEM2 [10], Knossos [11], CATMAID [12], SegEM [6], Ilastik [13], AxonSeg [14], Axon-DeepSeg [15], or MyelTracer [16], and proprietary software such as Amira (Thermofisher Scientific T M , MA, www.thermofisher.com/amira-avizo) or Imaris (Oxford Instruments, Abingdon, UK, www.imaris. oxinst.com).…”

Section: Introductionmentioning

confidence: 99%

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gACSON software for automated segmentation and morphology analyses of myelinated axons in 3D electron microscopy

Beháňová¹,

Abdollahzadeh²,

Belevich³

et al. 2021

Preprint

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Background and Objective: Advances in electron microscopy (EM) now allow three-dimensional (3D) imaging of hundreds of micrometers of tissue with nanometer-scale resolution, providing new opportunities to study the ultrastructure of the brain. In this work, we introduce a freely available gACSON software for visualization, segmentation, assessment, and morphology analysis of myelinated axons in 3D-EM volumes of brain tissue samples. Methods: The gACSON software is equipped with a graphical user interface (GUI). It automatically segments the intra-axonal space of myelinated axons and their corresponding myelin sheaths and allows manual segmentation, proofreading, and interactive correction of the segmented components. gACSON analyzes the morphology of myelinated axons, such as axonal diameter, axonal eccentricity, myelin thickness, or g-ratio. Results: We illustrate the use of gACSON by segmenting and analyzing myelinated axons in six 3D-EM volumes of rat somatosensory cortex after sham surgery or traumatic brain injury (TBI). Our results suggest that the equivalent diameter of myelinated axons in somatisensory cortex was decreased in TBI animals five months after the injury. Conclusions: Our results indicate that gACSON is a valuable tool for visualization, segmentation, assessment, and morphology analysis of myelinated axons in 3D-EM volumes. gACSON is freely available at https://github.com/AndreaBehan/g-ACSON under the MIT license.

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Central projections of auditory nerve fibers in the western rat snake (Pantherophis obsoletus)

Han

Carr

2023

J of Comparative Neurology

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Despite the absence of tympanic middle ears, snakes can hear. They are thought to primarily detect substrate vibration via connections between the lower jaw and the inner ear. We used the western rat snake (Pantherophis obsoletus) to determine how vibration is processed in the brain. We measured vibration‐evoked potential recordings to reveal sensitivity to low‐frequency vibrations. We then used tract tracing combined with immunohistochemistry and Nissl staining to describe the central projections of the papillar branch of the VIIIth nerve. Applications of biotinylated dextran amine to the basilar papilla (homologous to the organ of Corti of mammals) labeled bouton‐like terminals in two first‐order cochlear nuclei, a rostrolateral nucleus angularis (NA) and a caudomedial nucleus magnocellularis (NM). NA formed a distinct dorsal eminence, consisted of heterogenous cell types, and was parvalbumin positive. NM was smaller and poorly separated from the surrounding vestibular nuclei. NM was distinguished by positive calbindin label and included fusiform and round cells. Thus, the atympanate western rat snake shares similar first‐order projections to tympanate reptiles. Auditory pathways may be used for detecting vibration, not only in snakes but also potentially in atympanate early tetrapods.

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MyelTracer: A Semi-Automated Software for Myeling-Ratio Quantification

Abstract: MyelTracer: A semi-automated software for myelin g-ratio quantification Abbreviated Title (50 character maximum)Myelin g-ratio software 3. List all Author Names and Affiliations in order as they would appear in the published article

Cited by 56 publications

References 28 publications

Impaired oligodendrocyte maturation is an early feature in SCA3 disease pathogenesis

Impaired oligodendrocyte maturation is an early feature in SCA3 disease pathogenesis

gACSON software for automated segmentation and morphology analyses of myelinated axons in 3D electron microscopy

Central projections of auditory nerve fibers in the western rat snake (Pantherophis obsoletus)

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