Neurodevelopmental disorders—high-resolution rethinking of disease modeling

Khodosevich, Konstantin; Sellgren, Carl M.

doi:10.1038/s41380-022-01876-1

Cited by 16 publications

(18 citation statements)

References 90 publications

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“…h, Volumetric brain growth chart during early postnatal mouse development. All brain region volumes (mm 3 ) are reported as the mean ± standard deviation (s.d. ; shaded area between error bars) (total n=38; see Extended Data Table 2).…”

Section: Resultsmentioning

confidence: 99%

“…2a ) 29 . Our cell counting pipeline produces an organized data output of volume (mm 3 ), counted cells, and cell densities (cells/mm 3 ) for each anatomical brain region ( Extended Data Tables 3-6 ). Additionally, this workflow can be customized to work with STPT data acquired at various resolutions, as well as other high-resolution imaging data (e.g., light sheet fluorescence microscopy).…”

Section: Resultsmentioning

confidence: 99%

“… a , Overview of cell type mapping pipeline b, 3D renderings of Gad2 cell density (cells/mm 3 ) registered to age-matched epDevAtlas. Each processed image per age is from a representative Gad2-IRES-Cre;Ai14 brain sample.…”

Section: Resultsmentioning

confidence: 99%

“… a-b , Representative STPT images of Gad2 cells in the ( a ) primary somatosensory cortex (SSp) and ( b ) primary auditory cortex (AUDp). c, Temporal trajectory of Gad2 cell count vs. volume (mm 3 ) in the isocortex. d, Averaged Gad2 cell density patterns across isocortical areas.…”

Section: Resultsmentioning

confidence: 99%

“…Brain development during the first two postnatal weeks after birth in rodents is equivalent to the late gestation through perinatal periods in humans. It features well-orchestrated and diverse events including generation and migration of neurons and non-neuronal cells, programmed cell death, and formation of synapses in a rapidly expanding brain volume [3][4][5][6] . Specifically, γ-Aminobutyric acid-producing (GABAergic) cell development plays a critical role in establishing network excitatory-inhibitory balance in coordination with glutamatergic cells [7][8][9] .…”

Section: Introductionmentioning

confidence: 99%

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epDevAtlas: Mapping GABAergic cells and microglia in postnatal mouse brains

Liwang,

Kronman,

Minteer

et al. 2023

Preprint

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During development, brain regions follow encoded growth trajectories. Compared to classical brain growth charts, high-definition growth charts could quantify regional volumetric growth and constituent cell types, improving our understanding of typical and pathological brain development. Here, we create high-resolution 3D atlases of the early postnatal mouse brain, using Allen CCFv3 anatomical labels, at postnatal days (P) 4, 6, 8, 10, 12, and 14, and determine the volumetric growth of different brain regions. We utilize 11 different cell type-specific transgenic animals to validate and refine anatomical labels. Moreover, we reveal region-specific density changes in γ-aminobutyric acid-producing (GABAergic), cortical layer-specific cell types, and microglia as key players in shaping early postnatal brain development. We find contrasting changes in GABAergic neuronal densities between cortical and striatal areas, stabilizing at P12. Moreover, somatostatin-expressing cortical interneurons undergo regionally distinct density reductions, while vasoactive intestinal peptide-expressing interneurons show no significant changes. Remarkably, microglia transition from high density in white matter tracks to gray matter at P10, and show selective density increases in sensory processing areas that correlate with the emergence of individual sensory modalities. Lastly, we create an open-access web-visualization (https://kimlab.io/brain-map/epDevAtlas) for cell-type growth charts and developmental atlases for all postnatal time points.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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epDevAtlas: Mapping GABAergic cells and microglia in postnatal mouse brains

Liwang,

Kronman,

Minteer

et al. 2023

Preprint

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Microglial contribution to the pathology of neurodevelopmental disorders in humans

Matuleviciute,

Akinluyi,

Muntslag

et al. 2023

Acta Neuropathol

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Microglia are the brain’s resident macrophages, which guide various developmental processes crucial for brain maturation, activity, and plasticity. Microglial progenitors enter the telencephalic wall by the 4th postconceptional week and colonise the fetal brain in a manner that spatiotemporally tracks key neurodevelopmental processes in humans. However, much of what we know about how microglia shape neurodevelopment comes from rodent studies. Multiple differences exist between human and rodent microglia warranting further focus on the human condition, particularly as microglia are emerging as critically involved in the pathological signature of various cognitive and neurodevelopmental disorders. In this article, we review the evidence supporting microglial involvement in basic neurodevelopmental processes by focusing on the human species. We next concur on the neuropathological evidence demonstrating whether and how microglia contribute to the aetiology of two neurodevelopmental disorders: autism spectrum conditions and schizophrenia. Next, we highlight how recent technologies have revolutionised our understanding of microglial biology with a focus on how these tools can help us elucidate at unprecedented resolution the links between microglia and neurodevelopmental disorders. We conclude by reviewing which current treatment approaches have shown most promise towards targeting microglia in neurodevelopmental disorders and suggest novel avenues for future consideration.

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Possible roles of deep cortical neurons and oligodendrocytes in the neural basis of human sociality

Usui

2023

Anat Sci Int

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Sociality is an instinctive property of organisms that live in relation to others and is a complex characteristic of higher order brain functions. However, the evolution of the human brain to acquire higher order brain functions, such as sociality, and the neural basis for executing these functions and their control mechanisms are largely unknown. Several studies have attempted to evaluate how human sociality was acquired during the course of evolution and the mechanisms controlling sociality from a neurodevelopment viewpoint. This review discusses these findings in the context of human brain evolution and the pathophysiology of autism spectrum disorder (ASD). Comparative genomic studies of postmortem primate brains have demonstrated human-specific regulatory mechanisms underlying higher order brain functions, providing evidence for the contribution of oligodendrocytes to human brain function. Functional analyses of the causative genes of ASD in animal models have demonstrated that the neural basis of social behavior is associated with layer 6 (L6) of the neocortex and oligodendrocytes. These findings demonstrate that both neurons and oligodendrocytes contribute to the neural basis and molecular mechanisms underlying human brain evolution and social functioning. This review provides novel insights into sociability and the corresponding neural bases of brain disorders and evolution.

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Neurodevelopmental disorders—high-resolution rethinking of disease modeling

Cited by 16 publications

References 90 publications

epDevAtlas: Mapping GABAergic cells and microglia in postnatal mouse brains

epDevAtlas: Mapping GABAergic cells and microglia in postnatal mouse brains

Microglial contribution to the pathology of neurodevelopmental disorders in humans

Possible roles of deep cortical neurons and oligodendrocytes in the neural basis of human sociality

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