Historical Context

Rezaie, Payam; Hanisch, Uwe‐Karsten

doi:10.1007/978-1-4939-1429-6_2

Cited by 6 publications

(14 citation statements)

References 237 publications

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“… Table of the different terms used by the listed authors to designate glial cells, and their opinion on their presumed origin and function. Thorough accounts on the history of their discoveries can be found elsewhere (Rezaie and Hanisch, 2014 ). After Virchow coined the term “neuroglia” in the mid-nineteenth century to describe a substance that connected neurons, different researchers observed what seemed to be different types of glial cells in a variety of pathological conditions.…”

Section: The Discovery Of Microgliamentioning

confidence: 99%

“…After graduating as a medical doctor at the University of Madrid, Spain in 1904, Achúcarro traveled to Munich, Germany, to work in Alois Alzheimer's lab as a scientist and psychiatrist. There he became interested in neuroglia, and particularly in the rod cells (Stäbchenzellen ), a cell type that Franz Nissl had discovered in 1898 while observing human autopsy cases of mentally ill patients with paralysis (Vitoria Ortiz, 1977 ; Rezaie and Hanisch, 2014 ). Achúcarro was able to visualize these cells in the brains of rabbits infected with rabies or damaged by focal or inflammatory injury using a Scharlach Red (specific for fatty tissue) and hematoxylin (which stains nuclei) staining.…”

Section: The Discovery Of Microgliamentioning

confidence: 99%

“…Notwithstanding his great scientific contributions and large body of publications, Río-Hortega entered in strife with some members of the Cajal School and Cajal himself (Cano Diaz, 1985 ; Rezaie and Hanisch, 2014 ). It is unclear whether behind this conflict were purely scientific reasons or more personal problems (Cano Diaz, 1985 ).…”

Section: The Discovery Of Microgliamentioning

confidence: 99%

“…It is unclear whether behind this conflict were purely scientific reasons or more personal problems (Cano Diaz, 1985 ). The fact is that Río-Hortega's findings contradicted Cajal's view of the “third element” and that he left Cajal's lab in 1919 to establish his own lab back at the Student's Residency in 1920 (Cano Diaz, 1985 ; Rezaie and Hanisch, 2014 ). Río-Hortega was particularly involved with the search for simple, specific, and replicable methods to stain the nervous tissue, because he acknowledged, like Cajal before him, that novel findings required novel techniques (Cano Diaz, 1985 ).…”

Section: The Discovery Of Microgliamentioning

confidence: 99%

“…He acquired the methods of Cajal and Achúcarro, of Golgi and others and developed many variations, among them his famous silver carbonate method (a modification of Achúcarro's ammoniacal silver method) which provided an exceptional visualization of glial cells (Río-Hortega, 1916 , 1917 ). With this method, Río Hortega was able to obtain smaller micelles that impregnated the finest details of the brain tissue (Rezaie and Hanisch, 2014 ) and revealed in great depth the morphology of what he classified as two independent cell types: microglia and interstitial cells (which he later named oligodendrocytes) (Río-Hortega, 1919a , b , c ). Río-Hortega also realized that these two cell types were in fact what Cajal had called “adendritic” cells and that the master had not been able to discriminate between them because of an incomplete visualization of their processes using the sublimated gold chloride method of staining.…”

Section: The Discovery Of Microgliamentioning

confidence: 99%

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From the Cajal alumni Achúcarro and Río-Hortega to the rediscovery of never-resting microglia

et al. 2015

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Under the guidance of Ramón y Cajal, a plethora of students flourished and began to apply his silver impregnation methods to study brain cells other than neurons: the neuroglia. In the first decades of the twentieth century, Nicolás Achúcarro was one of the first researchers to visualize the brain cells with phagocytic capacity that we know today as microglia. Later, his pupil Pío del Río-Hortega developed modifications of Achúcarro's methods and was able to specifically observe the fine morphological intricacies of microglia. These findings contradicted Cajal's own views on cells that he thought belonged to the same class as oligodendroglia (the so called “third element” of the nervous system), leading to a long-standing discussion. It was only in 1924 that Río-Hortega's observations prevailed worldwide, thus recognizing microglia as a unique cell type. This late landing in the Neuroscience arena still has repercussions in the twenty first century, as microglia remain one of the least understood cell populations of the healthy brain. For decades, microglia in normal, physiological conditions in the adult brain were considered to be merely “resting,” and their contribution as “activated” cells to the neuroinflammatory response in pathological conditions mostly detrimental. It was not until microglia were imaged in real time in the intact brain using two-photon in vivo imaging that the extreme motility of their fine processes was revealed. These findings led to a conceptual revolution in the field: “resting” microglia are constantly surveying the brain parenchyma in normal physiological conditions. Today, following Cajal's school of thought, structural and functional investigations of microglial morphology, dynamics, and relationships with neurons and other glial cells are experiencing a renaissance and we stand at the brink of discovering new roles for these unique immune cells in the healthy brain, an essential step to understand their causal relationship to diseases.

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Section: The Discovery Of Microgliamentioning

confidence: 99%

Section: The Discovery Of Microgliamentioning

confidence: 99%

Section: The Discovery Of Microgliamentioning

confidence: 99%

Section: The Discovery Of Microgliamentioning

confidence: 99%

Section: The Discovery Of Microgliamentioning

confidence: 99%

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From the Cajal alumni Achúcarro and Río-Hortega to the rediscovery of never-resting microglia

et al. 2015

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Microglia states and nomenclature: A field at its crossroads

Paolicelli

Sierra

Stevens

et al. 2022

Neuron

869

504

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Lipid-nanoparticle-induced vacuolization in microglia

Kerschbaum,

Gerner,

Oberascher

et al. 2024

Commun Biol

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Lipid-containing vacuoles in microglia were discovered more than one hundred years ago in the brain of patients showing neurodegenerative processes. Recently, molecular-biological studies demonstrated specific changes in lipid-metabolism related to neurodegeneration. Despite that already Alzheimer described a distinct glia phenotype having large, lipid-containing vacuoles ( Gitterzellen ), little is known about how microglia convert lipid metabolites into a vacuolated phenotype. We studied the impact of liver-derived, insoluble, lipid-enriched nanoparticles (Lef-NP) ( ~ 20 nm) and of ceramide-coated Percoll-nanoparticles (Cer-NP) ( ~ 20 nm) on vacuolization in microglia. Lipidomic analysis of Lef-NP revealed numerous distinct lipids, including pro-inflammatory ceramides, which are enriched in the brain of Alzheimer patients. Video microscopy revealed that hepatocyte-derived Lef-NP and Cer-NP enhanced macropinocytosis, followed by macropinosome swelling and formation of the Gitterzellen phenotype. Neither ceramide nor Percoll-nanoparticles induced Gitterzellen -formation. Electron-tomography visualized membrane contact-sites between nanoparticle-loaded endosomes, endoplasmic reticulum cisternae and mitochondria. Suppression of lipid-nanoparticle-induced Gitterzellen -formation by amiloride, which supresses macropinocytosis, and bafilomycin A, an endosomal acidification inhibitor, further confirmed a pinocytotic pathway in Gitterzellen -formation. Bafilomycin A also reversed Gitterzellen to a ramified microglia phenotype. Our experimental findings suggest that lipid-nanoparticles but not emulsified lipids provoke vacuolization in microglia, and provide a simple in-vitro model for a pathogenic process taking years in the human brain.

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Historical Context

Cited by 6 publications

References 237 publications

From the Cajal alumni Achúcarro and Río-Hortega to the rediscovery of never-resting microglia

From the Cajal alumni Achúcarro and Río-Hortega to the rediscovery of never-resting microglia

Microglia states and nomenclature: A field at its crossroads

Lipid-nanoparticle-induced vacuolization in microglia

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