Does Birth Trigger Cell Death in the Developing Brain?

Castillo‐Ruiz, Alexandra; Hite, Taylor A.; Yakout, Dina W.; Rosen, T. John; Forger, Nancy G.

doi:10.1523/eneuro.0517-19.2020

Cited by 11 publications

(10 citation statements)

References 60 publications

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“…Term-born mouse pups in the first postnatal week are commonly compared to preterm newborns, based on cortical development milestones (52,99). While direct comparison between developmental stages of mice and humans is difficult due to different rates of maturation, our results confirm previous findings of accelerated brain maturation after premature birth (73,94). Our results further highlight the utility of simple EEG measures in the clinical setting and set the stage for future longitudinal studies that will explore the relationship between 1/f slope and neurodevelopmental outcomes in the preterm population.…”

Section: Discussionsupporting

confidence: 90%

“…While hypoxia represents a severe injury, it may not recapitulate the effects of preterm birth alone. Birth itself is an environmental shock that can significantly affect neuronal and synaptic development (73,94). As the effects of preterm birth in the absence of other pathologies are unclear, our results highlight a need for multiple animal models to capture the variability in the degree of preterm birth-related brain injury.…”

Section: Discussionmentioning

confidence: 99%

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Preterm birth accelerates the maturation of spontaneous and resting activity in the visual cortex

Witteveen

McCoy

Holsworth

et al. 2023

Preprint

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Prematurity is among the leading risk factors for poor neurocognitive outcomes. Brains of preterm infants often show alterations in structure, connectivity, and electrical activity, but the underlying circuit mechanisms are unclear. Using electroencephalography (EEG) in preterm and term-born infants, we find that preterm birth accelerates the maturation of aperiodic EEG components including decreased spectral power in the theta and alpha bands and flattened 1/f slope. Using in vivo electrophysiology in preterm mice, we find that preterm birth mice also show a flattened 1/f slope. We further found that preterm birth in mice results in suppressed spontaneous firing of neurons in the primary visual cortex, and accelerated maturation of inhibitory circuits, as assessed through quantitative immunohistochemistry. In both mice and infants, preterm birth advanced the functional maturation of the cortex. Our studies identify specific effects of preterm birth on the spectral composition of the infant EEG, and point to a potential mechanism of these effects, highlighting the utility of our parallel approach in studying the neural circuit mechanisms of preterm birth-related brain injury.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Preterm birth accelerates the maturation of spontaneous and resting activity in the visual cortex

Witteveen

McCoy

Holsworth

et al. 2023

Preprint

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“…Based on these findings, we isolated the fetal brain 24 h after exposure to hypoxia and normoxia (at E18.5). We elected to use animals that had not been born yet to avoid any confounding effects of early birth on neuronal cell death [63]. A neuropathologist (A.N.V.)…”

Section: Resultsmentioning

confidence: 99%

Deficits in Seizure Threshold and Other Behaviors in Adult Mice without Gross Neuroanatomic Injury after Late Gestation Transient Prenatal Hypoxia

Cristancho¹,

Gadra²,

Samba³

et al. 2022

Dev Neurosci

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Intrauterine hypoxia is a common cause of brain injury in children resulting in a broad spectrum of long-term neurodevelopmental sequela, including life-long disabilities that can occur even in the absence of severe neuroanatomic damage. Postnatal hypoxia-ischemia rodent models are commonly used to understand the effects of ischemia and transient hypoxia on the developing brain. Postnatal models, however, have some limitations. First, they do not test the impact of placental pathologies on outcomes from hypoxia. Second, they primarily recapitulate severe injury because they provoke substantial cell death, which is not seen in children with mild hypoxic injury. Lastly, they do not model preterm hypoxic injury. Prenatal models of hypoxia in mice may allow us to address some of these limitations to expand our understanding of developmental brain injury. The published rodent models of prenatal hypoxia employ multiple days of hypoxic exposure or complicated surgical procedures, making these models challenging to perform consistently in mice. Furthermore, large animal models suggest that transient prenatal hypoxia without ischemia is sufficient to lead to significant functional impairment to the developing brain. However, these large animal studies are resource-intensive and not readily amenable to mechanistic molecular studies. Therefore, here we characterized the effect of late gestation (embryonic day 17.5) transient prenatal hypoxia (5% inspired oxygen) on long-term anatomical and neurodevelopmental outcomes in mice. Late gestation transient prenatal hypoxia increased hypoxia-inducible factor 1 alpha protein levels (a marker of hypoxic exposure) in the fetal brain. Hypoxia exposure predisposed animals to decreased weight at postnatal day 2, which normalized by day 8. However, hypoxia did not affect gestational age at birth, litter size at birth, or pup survival. No differences in fetal brain cell death or long-term gray or white matter changes resulted from hypoxia. Animals exposed to prenatal hypoxia did have several long-term functional consequences, including sex-dichotomous changes. Hypoxia exposure was associated with a decreased seizure threshold and abnormalities in hindlimb strength and repetitive behaviors in males and females. Males exposed to hypoxia had increased anxiety-related deficits, whereas females had deficits in social interaction. Neither sex developed any motor or visual learning deficits. This study demonstrates that late gestation transient prenatal hypoxia in mice is a simple, clinically relevant paradigm for studying putative environmental and genetic modulators of the long-term effects of hypoxia on the developing brain.

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“…Intriguingly, premature birth leads to advanced neuronal cell death if cell death rates are compared as a function of post-conception age. Conversely, a delayed birth does not delay the rate of programmed cell death [135]. It is therefore suggested that programmed cell death follows an intrinsic developmental program that can be accelerated by an advanced birth.…”

Section: Control Of Apoptosismentioning

confidence: 99%

Development, Diversity, and Death of MGE-Derived Cortical Interneurons

Williams

Riedemann

2021

IJMS

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In the mammalian brain, cortical interneurons (INs) are a highly diverse group of cells. A key neurophysiological question concerns how each class of INs contributes to cortical circuit function and whether specific roles can be attributed to a selective cell type. To address this question, researchers are integrating knowledge derived from transcriptomic, histological, electrophysiological, developmental, and functional experiments to extensively characterise the different classes of INs. Our hope is that such knowledge permits the selective targeting of cell types for therapeutic endeavours. This review will focus on two of the main types of INs, namely the parvalbumin (PV+) or somatostatin (SOM+)-containing cells, and summarise the research to date on these classes.

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Does Birth Trigger Cell Death in the Developing Brain?

Cited by 11 publications

References 60 publications

Preterm birth accelerates the maturation of spontaneous and resting activity in the visual cortex

Preterm birth accelerates the maturation of spontaneous and resting activity in the visual cortex

Deficits in Seizure Threshold and Other Behaviors in Adult Mice without Gross Neuroanatomic Injury after Late Gestation Transient Prenatal Hypoxia

Development, Diversity, and Death of MGE-Derived Cortical Interneurons

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