The Special Case of Human Astrocytes

Verkhratsky, Alexei; Bush, Nancy Ann Oberheim; Nedergaard, Maiken; Butt, Arthur M.

doi:10.3390/neuroglia1010004

Cited by 41 publications

(43 citation statements)

References 47 publications

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“…Astrocytes also define many aspects of synapse formation, plasticity, protective function, synaptic maintenance, and elimination [26,27]. It is important to note, however, that human studies may not always conform to findings in rodents because human protoplasmic astrocytes in the neocortex are much larger and extend longer than in rodent models [28].…”

Section: Protoplasmic Astrocyte Remodeling In Cortical Gray Matter DImentioning

confidence: 99%

Ultrastructural Remodeling of the Neurovascular Unit in the Female Diabetic db/db Model—Part I: Astrocyte

et al. 2018

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Obesity, insulin resistance, and type 2 diabetes mellitus are associated with cognitive impairment, known as diabetic cognopathy. In this study, we tested the hypothesis that neurovascular unit(s) (NVU) within cerebral cortical gray matter regions display abnormal cellular remodeling. The monogenic (Leprdb) female diabetic db/db (BKS.CgDock7m +/+Leprdb/J; DBC) mouse model was utilized for this ultrastructural study. Upon sacrifice (at 20 weeks of age), left-brain hemispheres of the DBC and age-matched non-diabetic wild-type control C57BL/KsJ (CKC) mice were immediately immersion-fixed. We found attenuation/loss of endothelial blood–brain barrier tight/adherens junctions and pericytes, thickening of the basement membrane, aberrant mitochondria, and pathological remodeling of protoplasmic astrocytes. Additionally, there were adherent red blood cells and NVU microbleeds (cortical layer III) in DBC mice, which were not observed in CKC animals. While this study represents only a “snapshot in time”, it does allow for cellular remodeling comparisons between DBC and CKC. In this paper, the first of a three-part series, we report the observational ultrastructural remodeling changes of the NVU and its protoplasmic astrocytes in relation to the surrounding neuropil. Having identified multiple abnormal cellular remodeling changes in the DBC as compared to CKC models, we will design future experiments to evaluate various treatment modalities in DBC mice.

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Section: Protoplasmic Astrocyte Remodeling In Cortical Gray Matter DImentioning

confidence: 99%

Ultrastructural Remodeling of the Neurovascular Unit in the Female Diabetic db/db Model—Part I: Astrocyte

et al. 2018

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“…These trends argue against the concept that a high GNR reflects evolutionary advance and increased intelligence. Nonetheless, it is important to be aware that evolution brought with it substantial changes in the morphology and complexity of astroglia in the human cortex, which also contains several idiosyncratic types of glial cell [40][41][42]. However, astrocyte three-dimensional morphology has been systematically studied in too few species so far and none in brains larger than humans.…”

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confidence: 99%

“…complexity of astroglia in the human cortex, which also contains several idiosyncratic types of glial cell [40][41][42]. However, astrocyte three-dimensional morphology has been systematically studied in too few species so far and none in brains larger than humans.…”

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confidence: 99%

The History of the Decline and Fall of the Glial Numbers Legend

Verkhratsky

Butt

2018

Neuroglia

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In the field of neuroscience and, more specifically glial cell biology, one of the most fundamentally intriguing and enduring questions has been “how many neuronal cells—neurones and glia—are there in the human brain?”. From the outset, the driving force behind this question was undoubtedly the scientific quest for knowledge of why humans are more intelligent than even our nearest relatives; the ‘neuronal doctrine’ dictated we must have more neurones than other animals. The early histological studies indicated a vast space between neurones that was filled by ‘nervenkitt’, later identified as neuroglia; arguably, this was the origin of the myth that glia massively outnumber neurones in the human brain. The myth eventually became embedded in ideology when later studies seemed to confirm that glia outnumber neurones in the human cortex—the seat of humanity—and that there was an inevitable rise in the glia-to-neurone ratio (GNR) as we climbed the evolutionary tree. This could be described as the ‘glial doctrine’—that the rise of intelligence and the rise of glia go hand-in-hand. In many ways, the GNR became a mantra for working on glial cells at a time when the neuronal doctrine ruled the world. However, the work of Suzana Herculano-Houzel which she reviews in this first volume of Neuroglia has led the way in demonstrating that neurones and glia are almost equal in number in the human cortex and there is no inexorable phylogenetic rise in the GNR. In this commentary we chart the fall and decline of the mythology of the GNR.

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“…This latter form occurs only in humans, accounts for an absolute majority (~99%) of clinical pathology and cannot be reproduced in animals. In addition, human astrocytes differ fundamentally from astrocytes of rodents in their size, complexity and specific forms . In consequence experiments on AD‐affected human, astrocytes are to be conceived.…”

mentioning

confidence: 99%

“…In addition, human astrocytes differ fundamentally from astrocytes of rodents in their size, complexity and specific forms. 14 In consequence experiments on AD-affected human, astrocytes are to be conceived. How human astroglia can be experimentally interrogated?…”

mentioning

confidence: 99%