Construction of a rat spinal cord atlas of axon morphometry

Saliani, Ariane; Zaimi, Aldo; Nami, Harris; Duval, Tanguy; Stikov, Nikola; Cohen‐Adad, Julien

doi:10.1016/j.neuroimage.2019.116156

Cited by 8 publications

(15 citation statements)

References 54 publications

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“…This enables rapid analysis of larger datasets such as entire nerve cross-sections and thereby overcomes the need for sampling and the associated risk of sampling bias 3 , 9 , 10 . In conjunction with high-throughput whole-slide scanning technologies, tools such as AxonDeepSeg further allow for analysis of almost unlimited numbers of slides per nerve in experimental animals and human patients and therefore, may help to transform histomorphometric analysis from a laborious manual task to a component of big data precision medicine 39 , 40 .…”

Section: Discussionmentioning

confidence: 99%

Rapid, automated nerve histomorphometry through open-source artificial intelligence

Daeschler

Bourget

Derakhshan

et al. 2022

Sci Rep

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We aimed to develop and validate a deep learning model for automated segmentation and histomorphometry of myelinated peripheral nerve fibers from light microscopic images. A convolutional neural network integrated in the AxonDeepSeg framework was trained for automated axon/myelin segmentation using a dataset of light-microscopic cross-sectional images of osmium tetroxide-stained rat nerves including various axonal regeneration stages. In a second dataset, accuracy of automated segmentation was determined against manual axon/myelin labels. Automated morphometry results, including axon diameter, myelin sheath thickness and g-ratio were compared against manual straight-line measurements and morphometrics extracted from manual labels with AxonDeepSeg as a reference standard. The neural network achieved high pixel-wise accuracy for nerve fiber segmentations with a mean (± standard deviation) ground truth overlap of 0.93 (± 0.03) for axons and 0.99 (± 0.01) for myelin sheaths, respectively. Nerve fibers were identified with a sensitivity of 0.99 and a precision of 0.97. For each nerve fiber, the myelin thickness, axon diameter, g-ratio, solidity, eccentricity, orientation, and individual x -and y-coordinates were determined automatically. Compared to manual morphometry, automated histomorphometry showed superior agreement with the reference standard while reducing the analysis time to below 2.5% of the time needed for manual morphometry. This open-source convolutional neural network provides rapid and accurate morphometry of entire peripheral nerve cross-sections. Given its easy applicability, it could contribute to significant time savings in biomedical research while extracting unprecedented amounts of objective morphologic information from large image datasets.

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Section: Discussionmentioning

confidence: 99%

Rapid, automated nerve histomorphometry through open-source artificial intelligence

Daeschler

Bourget

Derakhshan

et al. 2022

Sci Rep

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“…The quantitative analysis of image is completed by image J. The ratio of the length of the axon diameter to the length of the myelinated fiber is the G-ratio of the myelinated fiber [ 51 ].…”

Section: Methodsmentioning

confidence: 99%

Astrocytic SARM1 promotes neuroinflammation and axonal demyelination in experimental autoimmune encephalomyelitis through inhibiting GDNF signaling

et al. 2022

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Astrocytes are important components of the innate immune response in the central nervous system (CNS), involving in the inflammatory and neurotoxic responses that occur in CNS diseases, such as multiple sclerosis (MS). Recent studies have shown that SARM1 plays a critical role in axonal degeneration and inflammation. However, the detailed role of astrocytic SARM1 in MS remains unclear. Here, we established the MS model of mice - experimental autoimmune encephalomyelitis (EAE) and found that SARM1 was upregulated in astrocytes of the spinal cords of EAE mice. Moreover, conditional knockout of astrocytic SARM1 (SARM1GFAP-CKO mice, SARM1Aldh1L1-CKO mice) delayed EAE with later onset, alleviated the inflammatory infiltration, and inhibited the demyelination and neuronal death. Mechanically, RNA-seq revealed that the expression of glial-derived neurotrophic factor (GDNF) was upregulated in SARM1−/− astrocytes. Western blot and immunostaining further confirmed the upregulation of GDNF in spinal cord astrocytes of SARM1GFAP-CKO EAE mice. Interestingly, the downregulation of GDNF by streptozotocin (STZ, a drug used to downregulate GDNF) treatment worsened the deficits of SARM1GFAP-CKO EAE mice. These findings identify that astrocytic SARM1 promotes neuroinflammation and axonal demyelination in EAE by inhibiting the expression of GDNF, reveal the novel role of SARM1/GDNF signaling in EAE, and provide new therapeutic ideas for the treatment of MS.

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“…The analysis was performed with Image J. The G-ratios of myelinated fibers were calculated as the ratio of the axonal diameter to the myelinated fiber diameter as measured from different locations as described previously [ 50 ].…”

Section: Methodsmentioning

confidence: 99%

Astrocytic YAP prevents the demyelination through promoting expression of cholesterol synthesis genes in experimental autoimmune encephalomyelitis

Zhang

Liu

et al. 2021

Cell Death Dis

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Cholesterols are the main components of myelin, and are mainly synthesized in astrocytes and transported to oligodendrocytes and neurons in the adult brain. It has been reported that Hippo/yes-associated protein (YAP) pathways are involved in cholesterol synthesis in the liver, however, it remains unknown whether YAP signaling can prevent the demyelination through promoting cholesterol synthesis in experimental autoimmune encephalomyelitis (EAE), a commonly used animal model of multiple sclerosis characterized by neuroinflammation and demyelination. Here, we found that YAP was upregulated and activated in astrocytes of spinal cords of EAE mice through suppression of the Hippo pathway. YAP deletion in astrocytes aggravated EAE with earlier onset, severer inflammatory infiltration, demyelination, and more loss of neurons. Furthermore, we found that the neuroinflammation was aggravated and the proliferation of astrocytes was decreased in YAPGFAP-CKO EAE mice. Mechanically, RNA-seq revealed that the expression of cholesterol-synthesis pathway genes such as HMGCS1 were decreased in YAP−/− astrocytes. qPCR, western blot, and immunostaining further confirmed the more significant reduction of HMGCS1 in spinal cord astrocytes of YAPGFAP-CKO EAE mice. Interestingly, upregulation of cholesterol-synthesis pathways by diarylpropionitrile (DPN) (an ERβ-ligand, to upregulate the expression of HMGCS1) treatment partially rescued the demyelination deficits in YAPGFAP-CKO EAE mice. Finally, activation of YAP by XMU-MP-1 treatment promoted the expression of HMGCS1 in astrocytes and partially rescued the demyelination and inflammatory infiltration deficits in EAE mice. These findings identify unrecognized functions of astrocytic YAP in the prevention of demyelination through promoting cholesterol synthesis in EAE, and reveal a novel pathway of YAP/HMGCS1 for cholesterol synthesis in EAE pathology.

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Construction of a rat spinal cord atlas of axon morphometry

Cited by 8 publications

References 54 publications

Rapid, automated nerve histomorphometry through open-source artificial intelligence

Rapid, automated nerve histomorphometry through open-source artificial intelligence

Astrocytic SARM1 promotes neuroinflammation and axonal demyelination in experimental autoimmune encephalomyelitis through inhibiting GDNF signaling

Astrocytic YAP prevents the demyelination through promoting expression of cholesterol synthesis genes in experimental autoimmune encephalomyelitis

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