An update on the rod microglia variant in experimental and clinical brain injury and disease

Giordano, Katherine R.; Denman, Charlotte R.; Dubisch, Phoebe S; Akhter, Murtaza; Lifshitz, Jonathan

doi:10.1093/braincomms/fcaa227

Cited by 46 publications

(46 citation statements)

References 70 publications

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“…However, rod microglia were found to be significantly abundant in the parietal cortex but not the hippocampus of AD patients compared to healthy controls [4]. Rod microglia have also been observed in those with mutated C9orf72 whilst they were absent in age-matched controls whilst additionally, a high density of rod microglia in the grey matter of those with Down's Syndrome AD correlated to more severe pathological hallmarks compared to those just with AD [21].…”

Section: Alzheimer's Diseasementioning

confidence: 88%

“…When noxious stimuli are extensively prolonged, activated microglia may morph into the "amoeboid" state with a rounder, larger and more regularly shaped cell and very few or no processes (Figure 1) [16,18]. A recently re-discovered morphotype are "rod" microglia characterised by a long, sausage-shaped cell body with a few processes that may not always extend beyond the length of ramified microglia (Figure 1) [20,21]. Although emerging evidence has shown rod microglia localising near neurons and aligning itself along the nerve fibres, their exact function is still yet to be discovered [20][21][22][23].…”

Section: Microgliamentioning

confidence: 99%

“…A recently re-discovered morphotype are "rod" microglia characterised by a long, sausage-shaped cell body with a few processes that may not always extend beyond the length of ramified microglia (Figure 1) [20,21]. Although emerging evidence has shown rod microglia localising near neurons and aligning itself along the nerve fibres, their exact function is still yet to be discovered [20][21][22][23]. The final type is the amoeboid microglia, often referred to as the phagocytic type that moves to the site of damage and phagocytose dead or dying neurons and cell debris (Figure 1) [5,24].…”

Section: Microgliamentioning

confidence: 99%

“…By the time the first cognitive symptoms start to appear, roughly 20 years of irreversible neurodegeneration would already have occurred [100]. Although the exact pathogenesis is still unknown, microglial activation in the brain and retina has been associated with AD pathology [4,13,21,[99][100][101][102][103]. This highlights the unmet need for earlier detection of AD pathogenesis and that characterisation of microglia may be a potential answer to this dilemma.…”

Section: Alzheimer's Diseasementioning

confidence: 99%

“…Rod microglia may have a region-specific involvement in AD pathology [4,21]. For instance, when three brain regions of AD patient autopsies were examined, rod microglia were only seen in the parietal cortex and not in the hippocampus or temporal cortex [4].…”

Section: Alzheimer's Diseasementioning

confidence: 99%

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Retinal and Brain Microglia in Multiple Sclerosis and Neurodegeneration

Choi¹,

Guo²,

Cordeiro

2021

Cells

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Microglia are the resident immune cells of the central nervous system (CNS), including the retina. Similar to brain microglia, retinal microglia are responsible for retinal surveillance, rapidly responding to changes in the environment by altering morphotype and function. Microglia become activated in inflammatory responses in neurodegenerative diseases, including multiple sclerosis (MS). When activated by stress stimuli, retinal microglia change their morphology and activity, with either beneficial or harmful consequences. In this review, we describe characteristics of CNS microglia, including those in the retina, with a focus on their morphology, activation states and function in health, ageing, MS and other neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, glaucoma and retinitis pigmentosa, to highlight their activity in disease. We also discuss contradictory findings in the literature and the potential ways of reducing inconsistencies in future by using standardised methodology, e.g., automated algorithms, to enable a more comprehensive understanding of this exciting area of research.

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Section: Alzheimer's Diseasementioning

confidence: 88%

Section: Microgliamentioning

confidence: 99%

Section: Microgliamentioning

confidence: 99%

Section: Alzheimer's Diseasementioning

confidence: 99%

Section: Alzheimer's Diseasementioning

confidence: 99%

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Retinal and Brain Microglia in Multiple Sclerosis and Neurodegeneration

Choi¹,

Guo²,

Cordeiro

2021

Cells

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Micro‐diffusely abnormal white matter: An early multiple sclerosis lesion phase with intensified myelin blistering

Luchicchi,

Muñoz‐Gonzalez,

Halperin

et al. 2024

Ann Clin Transl Neurol

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ObjectiveMultiple sclerosis (MS) is a chronic central nervous system disease whose white matter lesion origin remains debated. Recently, we reported subtle changes in the MS normal appearing white matter (NAWM), presenting with an increase in myelin blisters and myelin protein citrullination, which may recapitulate some of the prodromal degenerative processes involved in MS pathogenesis. Here, to clarify the relevance of these changes for subsequent MS myelin degeneration we explored their prevalence in WM regions characterized by subtly reduced myelination (dubbed as micro‐diffusely abnormal white matter, mDAWM).MethodsWe used an in‐depth (immuno)histochemistry approach in 27 MS donors with histological presence of mDAWM and 5 controls. An antibody panel against degenerative markers was combined and the presence of myelin/axonal aberrations was analyzed and compared with the NAWM from the same cases/slices/regions.ResultsmDAWM‐defined areas exhibit ill‐defined borders, no signs of Wallerian degeneration, and they associate with visible veins. Remarkably, such areas present with augmented myelin blister frequency, enhanced prevalence of polar myelin phospholipids, citrullination, and degradation of myelin basic protein (MBP) when compared with the NAWM. Furthermore, enhanced reactivity of microglia/macrophages against citrullinated MBP was also observed in this tissue.InterpretationWe report a new histologically defined early phase in MS lesion formation, namely mDAWM, which lacks signs of Wallerian pathology. These results support the prelesional nature of the mDAWM. We conceptualize that evolution to pathologically evident lesions comprises the previously documented imbalance of axo‐myelinic units (myelin blistering) leading to their degeneration and immune system activation by released myelin components.

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Tau seeding and spreading in vivo is supported by both AD-derived fibrillar and oligomeric tau

et al. 2023

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Insoluble fibrillar tau, the primary constituent of neurofibrillary tangles, has traditionally been thought to be the biologically active, toxic form of tau mediating neurodegeneration in Alzheimer’s disease. More recent studies have implicated soluble oligomeric tau species, referred to as high molecular weight (HMW), due to their properties on size-exclusion chromatography, in tau propagation across neural systems. These two forms of tau have never been directly compared. We prepared sarkosyl-insoluble and HMW tau from the frontal cortex of Alzheimer patients and compared their properties using a variety of biophysical and bioactivity assays. Sarkosyl-insoluble fibrillar tau comprises abundant paired-helical filaments (PHF) as quantified by electron microscopy (EM) and is more resistant to proteinase K, compared to HMW tau, which is mostly in an oligomeric form. Sarkosyl-insoluble and HMW tau are nearly equivalent in potency in HEK cell bioactivity assay for seeding aggregates, and their injection reveals similar local uptake into hippocampal neurons in PS19 Tau transgenic mice. However, the HMW preparation appears to be far more potent in inducing a glial response including Clec7a-positive rod microglia in the absence of neurodegeneration or synapse loss and promotes more rapid propagation of misfolded tau to distal, anatomically connected regions, such as entorhinal and perirhinal cortices. These data suggest that soluble HMW tau has similar properties to fibrillar sarkosyl-insoluble tau with regard to tau seeding potential, but may be equal or even more bioactive with respect to propagation across neural systems and activation of glial responses, both relevant to tau-related Alzheimer phenotypes.

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An update on the rod microglia variant in experimental and clinical brain injury and disease

Cited by 46 publications

References 70 publications

Retinal and Brain Microglia in Multiple Sclerosis and Neurodegeneration

Retinal and Brain Microglia in Multiple Sclerosis and Neurodegeneration

Micro‐diffusely abnormal white matter: An early multiple sclerosis lesion phase with intensified myelin blistering

Tau seeding and spreading in vivo is supported by both AD-derived fibrillar and oligomeric tau

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