Axonal degeneration in an in vitro model of ischemic white matter injury

Cui, Yunkang; Jin, Xuelian; Choi, Dong‐Joo; Choi, Jun Young; Kim, Hyung Soon; Hwang, Dae Hyun; Kim, Byung Gon

doi:10.1016/j.nbd.2019.104672

Cited by 15 publications

(16 citation statements)

References 48 publications

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“…Our study demonstrates that IgLON5‐ab cause disorganization of the cytoskeleton in cultures of rat hippocampal neurons by producing lesions such as dystrophic neurites, axonal swellings, and other abnormalities similar to those seen in hypoxic conditions and early events of neurodegeneration in some studies or, to a much lesser degree, in untreated neurons owing to normal aging processes in long‐term cell cultures 9–11 . These effects in the cytoskeleton occurred in association with the irreversible decrease of neuronal surface IgLON5 clusters previously described 3 .…”

Section: Discussionsupporting

confidence: 71%

“…3 To evaluate the effects on the neuronal cytoskeleton, neurons were subsequently fixed, permeabilized, and incubated for 1 hour at room temperature with neurofilament‐M chain (1:4000, #ab9034; Abcam, Cambridge, UK) antibody followed by anti‐human IgG Alexa Fluor 488 (1:1000; Thermo‐Fisher Scientific, Waltham, MA) and anti‐rabbit IgG Alexa Fluor 594 (1:1000; Thermo‐Fisher Scientific). Hypoxic conditions (1% O 2 , 94% N 2 , 5% CO 2 , 37°C; ESCO cell culture incubator, Horsham, UK) were applied for 2 days consecutively to untreated neurons as a model of cytoskeletal damage 9 …”

Section: Methodsmentioning

confidence: 99%

“…Hypoxic conditions (1% O 2 , 94% N 2 , 5% CO 2 , 37 C; ESCO cell culture incubator, Horsham, UK) were applied for 2 days consecutively to untreated neurons as a model of cytoskeletal damage. 9 In initial experiments, neurons were also incubated with TAU-5 (1:500, AHB0042) and AT8 (1:500, MN1020) antibodies (Thermo-Fisher Scientific) to evaluate tau and hyperphosphorylated tau, respectively. To confirm the specificity of the effects of IgLON5-ab on the neuronal cytoskeleton, parallel experiments were conducted with neurons treated with IgLON5-ab-positive IgG preabsorbed with IgLON5-expressing HEK293 cells.…”

Section: Treatments Immunostaining and Immunoabsorptionmentioning

confidence: 99%

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Effects of IgLON5 Antibodies on Neuronal Cytoskeleton: A Link between Autoimmunity and Neurodegeneration

Landa

Gaig

Plagumà

et al. 2020

Annals of Neurology

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Anti-IgLON5 disease is a neurological disorder characterized by autoantibodies against IgLON5 and pathological evidence of neuronal-specific tau accumulation. Here, we report that patients' IgLON5 IgG, but not other cell-surface antibodies, disrupt the cytoskeletal organization in cultured rat hippocampal neurons, resulting in dystrophic neurites and axonal swelling. Adsorption of IgLON5 IgG with HEK293 cells expressing IgLON5 abrogated the indicated cytoskeletal changes. These findings, along with an increase of levels of neurofilaments in patients' cerebrospinal fluid, suggest that IgLON5 IgG, unlike other cell-surface antibodies, disrupts neuronal cytoskeleton maintenance, providing a link between autoimmunity and neurodegeneration.

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Section: Discussionsupporting

confidence: 71%

Section: Methodsmentioning

confidence: 99%

Section: Treatments Immunostaining and Immunoabsorptionmentioning

confidence: 99%

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Effects of IgLON5 Antibodies on Neuronal Cytoskeleton: A Link between Autoimmunity and Neurodegeneration

Landa

Gaig

Plagumà

et al. 2020

Annals of Neurology

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“…To quantify axon fragmentation, Sasaki and colleagues introduced the AxD index as the ratio of fragmented axon area versus total axonal area 14 . However, the AxD index did not include axonal swellings, which is another characteristic feature of degenerating axons 11,29 . Hence, the precise spatiotemporal role of axonal swellings in AxD remains elusive.…”

Section: Discussionmentioning

confidence: 99%

“…To quantify axon fragmentation, Sasaki and colleagues introduced the AxD index as the ratio of fragmented axon area versus total axonal area (Sasaki et al, 2009). However, the AxD index did not include axonal swellings, which are a characteristic feature of degenerating axons (Yong et al, 2019;Cui et al, 2020). Although other analyses considered axonal swellings as a morphological feature of AxD (Nikić et al, 2011;Yong et al, 2019), the approaches were time-consuming and required manual annotations.…”

Section: Discussionmentioning

confidence: 99%

Deep learning to decipher the progression and morphology of axonal degeneration

Palumbo

Gruening

Landt

et al. 2020

Preprint

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Different axonal degeneration (AxD) patterns have been described depending on the biological condition. Until now, it remains unclear whether they are restricted to one specific condition or can occur concomitantly. Here, we present a novel microfluidic device in combination with a deep learning tool, the EntireAxon, for the high-throughput analysis of AxD. We evaluated the progression of AxD in an in vitro model of hemorrhagic stroke and observed that axonal swellings preceded axon fragmentation. We further identified four distinct morphological patterns of AxD (granular, retraction, swelling, and transport degeneration) that occur concomitantly. These findings indicate a morphological heterogeneity of AxD under pathophysiologic conditions. The newly developed microfluidic device along with the EntireAxon deep learning tool enable the systematic analysis of AxD but also unravel a so far unknown intricacy in which AxD can occur in a disease context.

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Mechanisms of glutamate metabolic function and dysfunction in vascular dementia

Wang,

Zhang,

Tian

et al. 2024

Neuroprotection

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As the global population ages, research on the pathogenesis and treatment options for older patients with dementia has become increasingly important. Vascular dementia (VaD), the second most frequent type of dementia, is characterized by vascular impairment caused by inadequate blood supply to the brain. VaD is a complex neurological disorder involving multiple cells and signaling pathways, and its prevention and treatment pose clinical challenges with significant behavioral implications. Glutamate, the most abundant amino acid in the brain, plays a critical role as an excitatory neurotransmitter, impacting cognitive function, learning, and memory. Abnormal glutamate metabolism has been closely linked to dementia, and reduced blood flow to the brain can lead to excessive glutamate accumulation, resulting in neuronal death. This article highlights the connection between VaD and glutamate metabolism, aiming to identify better methods for preventing and treating VaD via regulating glutamate metabolism.

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Axonal degeneration in an in vitro model of ischemic white matter injury

Cited by 15 publications

References 48 publications

Effects of IgLON5 Antibodies on Neuronal Cytoskeleton: A Link between Autoimmunity and Neurodegeneration

Effects of IgLON5 Antibodies on Neuronal Cytoskeleton: A Link between Autoimmunity and Neurodegeneration

Deep learning to decipher the progression and morphology of axonal degeneration

Mechanisms of glutamate metabolic function and dysfunction in vascular dementia

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