An empirical analysis of the precision of estimating the numbers of neurons and glia in human neocortex using a fractionator-design with sub-sampling

Lyck, Lise; Santamaría, Ishar Dalmau; Pakkenberg, Bente; Chemnitz, J.; Schrøder, Henrik Daa; Finsen, Bente; Gundersen, Hans Jørgen G.

doi:10.1016/j.jneumeth.2009.06.003

Cited by 43 publications

(52 citation statements)

References 55 publications

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“…This shared functionality included microglia as the main cell type, extracellular matrix as the main cellular component, and immune response as the main biological process. Microglia, constituting 5%-12% of all cells in the mouse and human brain (Lawson et al 1990;Lyck et al 2009;Olah et al 2018) and primarily known for their role in immune response, have recently been implicated in multiple brain functions including the regulation of learning-related synapse formation, synaptic plasticity, and cognition (Parkhurst et al 2013;Hong et al 2016;Tay et al 2017) and are linked with neurodegenerative and psychiatric disorders (Wolf et al 2017). Furthermore, microglial cells were shown to have different transcriptional identities in different brain regions (Grabert et al 2016).…”

Section: Discussionmentioning

confidence: 99%

Human-specific features of spatial gene expression and regulation in eight brain regions

Efimova

et al. 2018

Genome Res.

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Molecular maps of the human brain alone do not inform us of the features unique to humans. Yet, the identification of these features is important for understanding both the evolution and nature of human cognition. Here, we approached this question by analyzing gene expression and H3K27ac chromatin modification data collected in eight brain regions of humans, chimpanzees, gorillas, a gibbon, and macaques. An analysis of spatial transcriptome trajectories across eight brain regions in four primate species revealed 1851 genes showing human-specific transcriptome differences in one or multiple brain regions, in contrast to 240 chimpanzee-specific differences. More than half of these human-specific differences represented elevated expression of genes enriched in neuronal and astrocytic markers in the human hippocampus, whereas the rest were enriched in microglial markers and displayed human-specific expression in several frontal cortical regions and the cerebellum. An analysis of the predicted regulatory interactions driving these differences revealed the role of transcription factors in species-specific transcriptome changes, and epigenetic modifications were linked to spatial expression differences conserved across species.

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Section: Discussionmentioning

confidence: 99%

Human-specific features of spatial gene expression and regulation in eight brain regions

Efimova

et al. 2018

Genome Res.

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“…Elephant neuromorphology may reflect a particular phylogenetic heritage and/or may be associated with the lower cell packing density in the cortex. Indeed, the elephant cortex appears to have a lower neuronal density than dolphins and primates (Haug 1987;Lyck et al 2009). These data, combined with calculations of total volume of cortex dedicated to somatic processing (Hofman 1982), suggest that elephants have approximately 10 billion non-somatic neurons spread across a large area of neocortex, compared to 6.5 billion tightly packed neurons for chimpanzees and 20 billion tightly packed neurons for humans (Hart et al 2008).…”

Section: Elephant Superficial Pyramidal Neurons and Human Supragranulmentioning

confidence: 99%

Neuronal morphology in the African elephant (Loxodonta africana) neocortex

et al. 2010

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Virtually nothing is known about the morphology of cortical neurons in the elephant. To this end, the current study provides the first documentation of neuronal morphology in frontal and occipital regions of the African elephant (Loxodonta africana). Cortical tissue from the perfusion-fixed brains of two free-ranging African elephants was stained with a modified Golgi technique. Neurons of different types (N=75), with a focus on superficial (i.e., layers II-III) pyramidal neurons, were quantified on a computer-assisted microscopy system using Neurolucida software. Qualitatively, elephant neocortex exhibited large, complex spiny neurons, many of which differed in morphology/orientation from typical primate and rodent pyramidal neurons. Elephant cortex exhibited a V-shaped arrangement of bifurcating apical dendritic bundles. Quantitatively, the dendrites of superficial pyramidal neurons in elephant frontal cortex were more complex than in occipital cortex. In comparison to human supragranular pyramidal neurons, elephant superficial pyramidal neurons exhibited similar overall basilar dendritic length, but the dendritic segments tended to be longer in the elephant with less intricate branching. Finally, elephant aspiny interneurons appeared to be morphologically consistent with other eutherian mammals. The current results thus elaborate on the evolutionary roots of Afrotherian brain organization and highlight unique aspects of neural architecture in elephants.

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“…Glia are further highly conserved throughout evolution and are, except for the cerebellum, the most abundant cell type in almost all subregions of the mammalian brain, suggesting an important role for these cells (Pfrieger and Barres, 1995). Studies experimentally quantifying glial cell numbers in mammalian brains have shown that in general, at least 50% of all cells in the human brain are glia, with considerable differences between studies and between different brain areas and a ratio that may change with age (Pelvig et al, 2008; Azevedo et al, 2009; Herculano-Houzel, 2009; Lyck et al, 2009). For example, the glia to neuron ratio of the cerebral cortex is approximately 3.76 and for the cerebellum 0.23 (Azevedo et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

The Indispensable Roles of Microglia and Astrocytes during Brain Development

Reemst

Noctor

Lucassen

et al. 2016

Front. Hum. Neurosci.

437

387

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Glia are essential for brain functioning during development and in the adult brain. Here, we discuss the various roles of both microglia and astrocytes, and their interactions during brain development. Although both cells are fundamentally different in origin and function, they often affect the same developmental processes such as neuro-/gliogenesis, angiogenesis, axonal outgrowth, synaptogenesis and synaptic pruning. Due to their important instructive roles in these processes, dysfunction of microglia or astrocytes during brain development could contribute to neurodevelopmental disorders and potentially even late-onset neuropathology. A better understanding of the origin, differentiation process and developmental functions of microglia and astrocytes will help to fully appreciate their role both in the developing as well as in the adult brain, in health and disease.

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An empirical analysis of the precision of estimating the numbers of neurons and glia in human neocortex using a fractionator-design with sub-sampling

Cited by 43 publications

References 55 publications

Human-specific features of spatial gene expression and regulation in eight brain regions

Human-specific features of spatial gene expression and regulation in eight brain regions

Neuronal morphology in the African elephant (Loxodonta africana) neocortex

The Indispensable Roles of Microglia and Astrocytes during Brain Development

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