In preprints: giving the developing brain the energy it needs DOI Creative Commons
Taylor R. Pennington, Madeline G. Andrews

Development, Journal Year: 2025, Volume and Issue: 152(2)

Published: Jan. 15, 2025

Metabolism is increasingly appreciated for its active role in tissue development during embryogenesis, particularly discrete instruction brain growth and formation. Catabolic programs are essential the breakdown of nutrients to provide energy anabolic processes that construct macromolecules cell structures required expansion organization (Rajan Fame, 2024). Nutrient availability environmental factors influence bioenergetic state developing cells, instruct cellular tissue-specific niches throughout embryogenesis (Traxler et al., 2021; Andrews Pearson, Intracellular metabolism uses external cues from maternal embryonic environments modify gene expression through epigenetic modifications genomic accessibility (Reid 2017; Sánchez-Ramírez Therefore, assessing relationship between metabolome developmental can insights into mechanisms regulate proliferation, differentiation maturation formation.A recent preprint by Saha colleagues highlights importance nutrient examining effects methionine restriction on cellular- tissue-level changes (Saha 2024 preprint). Methionine, conjunction with other metabolites, interconnected numerous metabolic pathways signaling cascades coordinate function (Sanderson 2019). This study evaluated impact dietary mice day (E) 9.5 gestation or exclusively neurogenesis. The results demonstrate neural progenitors display particular vulnerability, leading downstream decreases neurons astrocytes. Progenitors indicators quiescence suggested differentiation, markers. While restoring levels rescued neuron production, there were continued differences methylation marks, presumably compromised delayed gliogenesis. These findings prompt further questions about how substrates timing fate decisions.In addition availability, a Rodriguez Salazar evaluates mitochondrial dynamics astrocyte morphology rats (Salazar During postnatal development, astrocytes undergo structural functional progress mature state, shifting catabolic support increased demands (Zehnder Marina 2018). balance mitochondria fission, fusion transport coordinating specialized functions (Tábara authors discovered Drp-1-mediated fission enables localization distal higher degrees branching more-complex morphologies. resulting high content establish proper Cx43 gap junction protein abundance an evenly dispersed domain across cortex. Their indicate maturing astrocytes, which mediate complex intercellular, synaptic regulation. Notably, drives glycolytic activity due decreased oxidative phosphorylation efficiency ROS production (Zong 2024; Chen Chan, 2017). Mature have glycolysis influx lactate provides fuel surrounding neurons. morphological complexity supports cortical development.Collectively, these studies highlight unique requirements populations based their rodent Each indicates rewiring accommodate dynamic activities development. Metabolic progenitor cells progeny capacity self-renewal (Zhang 2018; Folmes 2012). consequences production. point response correspond altered quiescence, proliferation impaired neurogenesis gliogenesis, depending duration. focus supportive terminally differentiated later stages astrocytic maturation. Together, clarify stages. change, window, duration perturbation assessments distinct, both manuscripts observe disturbances glial whether In changes, alterations, either tiling territory spatial laminae. Collectively, cell-specific regulates may longitudinal health homeostasis.As describe, affect composition organizational features. Of note, had largest effect weight, compared organs, suggesting neurodevelopmental be vulnerable changes. particular, preferentially impacted, perhaps central nervous system (CNS) (Marina Xiong 2022). proportional decrease types catastrophic long-term (Jourdon 2023; Klingler 2021), also suggest certain pliability fluctuations rescue if reversed relevant windows. Restoration loss after reversal, Drp1 restored fission-regulated morphology. modulate potentially therapeutically target dysfunctional implicated neurological disease. A variety disorders, including autism attention deficit hyperactivity disorder (ADHD), errors metabolism; thus, understanding origins potential treatment valuable (Oyarzábal Pinto Payares 2024).Moving forward, measurements shifts determine bioenergetics affected Mitochondrial biosensors assess real-time, using microscopy (Cambronne 2016; Glancy, 2020). Metabolomic methods magnetic resonance (quantifiable) mass spectrometry (targeted untargeted) comprehensively characterize profiles map pathway isotopic tracers (Johnson Antoniewicz, use gold-standard cutting-edge technologies paired temporal lens will continue illuminate orchestrates programs.

Language: Английский

Brain malformations and seizures by impaired chaperonin function of TRiC DOI
Florian Kraft, Piere Rodriguez-Aliaga,

Weimin Yuan

et al.

Science, Journal Year: 2024, Volume and Issue: 386(6721), P. 516 - 525

Published: Oct. 31, 2024

Malformations of the brain are common and vary in severity, from negligible to potentially fatal. Their causes have not been fully elucidated. Here, we report pathogenic variants core protein-folding machinery TRiC/CCT individuals with malformations, intellectual disability, seizures. The chaperonin TRiC is an obligate hetero-oligomer, identify seven its eight subunits, all which impair function or assembly through different mechanisms. Transcriptome proteome analyses patient-derived fibroblasts demonstrate various consequences impairment. results reveal unexpected widespread role for protein folding development central nervous system define a disease spectrum "TRiCopathies."

Language: Английский

Citations

5
The Ferret as a Model System for Neocortex Development and Evolution DOI Creative Commons
Carlotta Gilardi, Nereo Kalebic

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: April 29, 2021

The neocortex is the largest part of cerebral cortex and a key structure involved in human behavior cognition. Comparison development across mammals reveals that proliferative capacity neural stem progenitor cells length neurogenic period are essential for regulating size complexity, which turn thought to be instrumental increased cognitive abilities humans. domesticated ferret, Mustela putorius furo , an important animal model neurodevelopment its complex postnatal cortical folding, long forebrain accessibility genetic manipulation vivo . Here, we discuss molecular, cellular, histological features make this small gyrencephalic carnivore suitable study physiological pathological mechanisms expanded neocortex. We particularly focus on cell proliferation, neuronal differentiation, visual system development, neurodevelopmental pathologies. further technological advances have enabled ferret Finally, compare with those other organisms.

Language: Английский

Citations

31
Multimodal mapping of regional brain vulnerability to focal cortical dysplasia DOI

Hyo M. Lee,

Seok‐Jun Hong, Ravnoor Gill

et al.

Brain, Journal Year: 2023, Volume and Issue: 146(8), P. 3404 - 3415

Published: Feb. 28, 2023

Abstract Focal cortical dysplasia (FCD) type II is a highly epileptogenic developmental malformation and common cause of surgically treated drug-resistant epilepsy. While clinical observations suggest frequent occurrence in the frontal lobe, mechanisms for such propensity remain unexplored. Here, we hypothesized that cortex-wide spatial associations FCD distribution with cytoarchitecture, gene expression organizational axes may offer complementary insights into processes predispose given regions to harbour FCD. We mapped MRI FCDs 337 patients collected from 13 sites worldwide. then determined its (i) cytoarchitectural features using histological atlases by Von Economo Koskinas BigBrain; (ii) whole-brain spatiotemporal dynamics prenatal adulthood stages Allen Human Brain Atlas PsychENCODE BrainSpan; (iii) macroscale organization. lesions were preferentially located prefrontal fronto-limbic cortices typified low neuron density, large soma thick grey matter. Transcriptomic uncovered component related neuroglial proliferation differentiation, likely accounting dysplastic makeup, postnatal synaptogenesis circuit organization, possibly contributing circuit-level hyperexcitability. showed strong association anterior region antero-posterior axis derived heritability analysis interregional structural covariance thickness, but not functional hierarchical axes. Reliability all results was confirmed through resampling techniques. Multimodal organization indicate neurogenesis be key points vulnerability lobe Concordant causal role atypical growth, our FCD-vulnerable display properties indicative earlier termination initiation cell growth. They also potential contribution aberrant development epileptogenicity.

Language: Английский

Citations

13
Cytoskeleton-modulating nanomaterials and their therapeutic potentials DOI
Jin-Won Park,

Yina Wu,

Jung Suk Kim

et al.

Advanced Drug Delivery Reviews, Journal Year: 2024, Volume and Issue: 211, P. 115362 - 115362

Published: June 19, 2024

Language: Английский

Citations

4
In preprints: giving the developing brain the energy it needs DOI Creative Commons
Taylor R. Pennington, Madeline G. Andrews

Development, Journal Year: 2025, Volume and Issue: 152(2)

Published: Jan. 15, 2025

Metabolism is increasingly appreciated for its active role in tissue development during embryogenesis, particularly discrete instruction brain growth and formation. Catabolic programs are essential the breakdown of nutrients to provide energy anabolic processes that construct macromolecules cell structures required expansion organization (Rajan Fame, 2024). Nutrient availability environmental factors influence bioenergetic state developing cells, instruct cellular tissue-specific niches throughout embryogenesis (Traxler et al., 2021; Andrews Pearson, Intracellular metabolism uses external cues from maternal embryonic environments modify gene expression through epigenetic modifications genomic accessibility (Reid 2017; Sánchez-Ramírez Therefore, assessing relationship between metabolome developmental can insights into mechanisms regulate proliferation, differentiation maturation formation.A recent preprint by Saha colleagues highlights importance nutrient examining effects methionine restriction on cellular- tissue-level changes (Saha 2024 preprint). Methionine, conjunction with other metabolites, interconnected numerous metabolic pathways signaling cascades coordinate function (Sanderson 2019). This study evaluated impact dietary mice day (E) 9.5 gestation or exclusively neurogenesis. The results demonstrate neural progenitors display particular vulnerability, leading downstream decreases neurons astrocytes. Progenitors indicators quiescence suggested differentiation, markers. While restoring levels rescued neuron production, there were continued differences methylation marks, presumably compromised delayed gliogenesis. These findings prompt further questions about how substrates timing fate decisions.In addition availability, a Rodriguez Salazar evaluates mitochondrial dynamics astrocyte morphology rats (Salazar During postnatal development, astrocytes undergo structural functional progress mature state, shifting catabolic support increased demands (Zehnder Marina 2018). balance mitochondria fission, fusion transport coordinating specialized functions (Tábara authors discovered Drp-1-mediated fission enables localization distal higher degrees branching more-complex morphologies. resulting high content establish proper Cx43 gap junction protein abundance an evenly dispersed domain across cortex. Their indicate maturing astrocytes, which mediate complex intercellular, synaptic regulation. Notably, drives glycolytic activity due decreased oxidative phosphorylation efficiency ROS production (Zong 2024; Chen Chan, 2017). Mature have glycolysis influx lactate provides fuel surrounding neurons. morphological complexity supports cortical development.Collectively, these studies highlight unique requirements populations based their rodent Each indicates rewiring accommodate dynamic activities development. Metabolic progenitor cells progeny capacity self-renewal (Zhang 2018; Folmes 2012). consequences production. point response correspond altered quiescence, proliferation impaired neurogenesis gliogenesis, depending duration. focus supportive terminally differentiated later stages astrocytic maturation. Together, clarify stages. change, window, duration perturbation assessments distinct, both manuscripts observe disturbances glial whether In changes, alterations, either tiling territory spatial laminae. Collectively, cell-specific regulates may longitudinal health homeostasis.As describe, affect composition organizational features. Of note, had largest effect weight, compared organs, suggesting neurodevelopmental be vulnerable changes. particular, preferentially impacted, perhaps central nervous system (CNS) (Marina Xiong 2022). proportional decrease types catastrophic long-term (Jourdon 2023; Klingler 2021), also suggest certain pliability fluctuations rescue if reversed relevant windows. Restoration loss after reversal, Drp1 restored fission-regulated morphology. modulate potentially therapeutically target dysfunctional implicated neurological disease. A variety disorders, including autism attention deficit hyperactivity disorder (ADHD), errors metabolism; thus, understanding origins potential treatment valuable (Oyarzábal Pinto Payares 2024).Moving forward, measurements shifts determine bioenergetics affected Mitochondrial biosensors assess real-time, using microscopy (Cambronne 2016; Glancy, 2020). Metabolomic methods magnetic resonance (quantifiable) mass spectrometry (targeted untargeted) comprehensively characterize profiles map pathway isotopic tracers (Johnson Antoniewicz, use gold-standard cutting-edge technologies paired temporal lens will continue illuminate orchestrates programs.

Language: Английский

Citations

0