Hypoxia and connectivity in the developing vertebrate nervous system

Bonkowsky, Joshua L.; Son, Jong-Hyun

doi:10.1242/dmm.037127

Cited by 22 publications

(17 citation statements)

References 127 publications

(157 reference statements)

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“…During embryogenesis, the developing nervous system requires precise regulation of oxygen levels. Low levels of oxygen induce Hif gene expression, which enhances the expression of epo to regulate erythrogenesis [ 61 ]. Our results indicated that the expression levels of hif1a and hif2a were reduced in B[a] P- treated embryos.…”

Section: Discussionmentioning

confidence: 99%

Integrated Hypoxia Signaling and Oxidative Stress in Developmental Neurotoxicity of Benzo[a]Pyrene in Zebrafish Embryos

Lin

et al. 2020

Antioxidants

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Benzo[a]pyrene (B[a]P) is a polycyclic aromatic hydrocarbon formed by the incomplete combustion of organic matter. Environmental B[a]P contamination poses a serious health risk to many organisms because the pollutant may negatively affect many physiological systems. As such, chronic exposure to B[a]P is known to lead to locomotor dysfunction and neurodegeneration in several organisms. In this study, we used the zebrafish model to delineate the acute toxic effects of B[a]P on the developing nervous system. We found that embryonic exposure of B[a]P downregulates shh and isl1, causing morphological hypoplasia in the telencephalon, ventral thalamus, hypothalamus, epiphysis and posterior commissure. Moreover, hypoxia-inducible factors (hif1a and hif2a) are repressed upon embryonic exposure of B[a]P, leading to reduced expression of the Hif-target genes, epo and survivin, which are associated with neural differentiation and maintenance. During normal embryogenesis, low-level oxidative stress regulates neuronal development and function. However, our experiments revealed that embryonic oxidative stress is greatly increased in B[a]P-treated embryos. The expression of catalase was decreased and sod1 expression increased in B[a]P-treated embryos. These transcriptional changes were coincident with increased embryonic levels of H2O2 and malondialdehyde, with the levels in B[a]P-treated fish similar to those in embryos treated with 120-μM H2O2. Together, our data suggest that reduced Hif signaling and increased oxidative stress are involved in B[a]P-induced acute neurotoxicity during embryogenesis.

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Section: Discussionmentioning

confidence: 99%

Integrated Hypoxia Signaling and Oxidative Stress in Developmental Neurotoxicity of Benzo[a]Pyrene in Zebrafish Embryos

Lin

et al. 2020

Antioxidants

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“…Therefore, the brain is prone to hypoxia or insufficient oxygen supply due to anemia. Hypoxia may interrupt the development of the brain's nervous system and cause a series of changes and damage to molecules and neurons [35].…”

Section: Association Of Anemia With Neurobehavioral Development Of Children Aged 6-24 Monthsmentioning

confidence: 99%

Association of Iron-Deficiency Anemia and Non-Iron-Deficiency Anemia with Neurobehavioral Development in Children Aged 6–24 Months

Zheng

Liu²,

Yang

2021

Nutrients

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(1) Background: Anemia has comprehensive adverse effects on the growth and development of children. In this study, we analyzed the potential effects of different types of anemia on early-life neurobehavioral development. (2) Methods: A total of 2601 children aged 6–24 months, whose parents agreed to participate in this study, underwent routine blood tests and neurobehavioral development assessment. The children’s parents or other primary caregivers were interviewed with a face-to-face questionnaire at the time of enrollment in the study. Anemia was determined by hemoglobin < 110 g/L and classified into iron-deficiency and non-iron-deficiency anemia according to the levels of serum ferritin, C-reactive protein, and alpha-1-acid glycoprotein. Neurobehavioral development was assessed by the China Developmental Scale for Children and divided into five domains: gross motor, fine movement, adaptability, language, and social behavior. The development quotient (DQ) was used to measure the level of total neurobehavioral development and each domain of neurobehavioral development. (3) Results: The prevalence of anemia in children aged 6–24 months was 26.45%, of which iron-deficiency anemia only accounted for 27.33%. Compared with children without anemia, those with iron-deficiency anemia had a significantly lower developmental quotient (DQ) for total neurobehavioral development and gross motor and adaptability development. The partial regression coefficients were −1.33 (95% CI −2.36, −0.29; p = 0.012), −1.88 (95% CI −3.74, −0.03; p = 0.047), and 1.48 (95% CI −2.92, −0.05; p = 0.042), respectively. Children with non-iron-deficiency anemia had significantly lower DQ for total neurobehavioral development and gross motor and fine movement development than those without anemia. The partial regression coefficients were −0.94 (95% CI −1.64, −0.25; p = 0.008), −1.25 (95% CI −2.48, −0.03; p = 0.044), and −1.18 (95% CI −2.15, −0.21; p = 0.017), respectively. There were no statistically significant differences in total neurobehavioral development and the five domains of neurobehavioral development between children with non-iron-deficiency and iron-deficiency anemia. The partial β values were 0.40 (95% CI −1.53, 2.33; p = 0.684), 0.21 (95% CI −1.39, 1.81; p = 0.795), 0.63 (95% CI −1.03, 2.28; p = 0.457), 0.16 (95% CI −1.78, 2.10; p = 0.871), 0.35 (95% CI −1.32, 2.01; p = 0.684), and 0.34 (95% CI −0.77, 1.46; p = 0.545), respectively. (4) Conclusions: Both iron-deficiency anemia and non-iron-deficiency anemia were negatively correlated with the neurobehavioral development of children. Negative correlations were found between iron-deficiency anemia and gross motor and adaptability development and between non-iron-deficiency anemia and gross motor and fine movement development.

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“…Exposure to Hx during preterm brain development is a significant risk factor for persistent neurodevelopmental disabilities (Poets et al, 2015;Bonkowsky and Son, 2018). Preterm neonates may sustain up to 600 transient hypoxic events per week (Di Fiore et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Transient Hypoxemia Disrupts Anatomical and Functional Maturation of Preterm Fetal Ovine CA1 Pyramidal Neurons

et al. 2019

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Children who survive premature birth often exhibit reductions in hippocampal volumes and deficits in working memory. However, it is unclear whether synaptic plasticity and cellular mechanisms of learning and memory can be elicited or disrupted in the preterm fetal hippocampus. CA1 hippocampal neurons were exposed to two common insults to preterm brain: transient hypoxia-ischemia (HI) and hypoxia (Hx). We used a preterm fetal sheep model using both sexes in twin 0.65 gestation fetuses that reproduces the spectrum of injury and abnormal growth in preterm infants. Using Cavalieri measurements, hippocampal volumes were reduced in both Hx and HI fetuses compared with controls. This volume loss was not the result of neuronal cell death. Instead, morphometrics revealed alterations in both basal and apical dendritic arborization that were significantly associated with the level of systemic hypoxemia and metabolic stress regardless of etiology. Anatomical alterations of CA1 neurons were accompanied by reductions in probability of presynaptic glutamate release, long-term synaptic plasticity and intrinsic excitability. The reduction in intrinsic excitability was in part due to increased activity of the channels underlying the fast and slow component of the afterhyperpolarization in Hx and HI. Our studies suggest that even a single brief episode of hypoxemia can markedly disrupt hippocampal maturation. Hypoxemia may contribute to long-term working memory disturbances in preterm survivors by disrupting neuronal maturation with resultant functional disturbances in hippocampal action potential throughput. Strategies directed at limiting the duration or severity of hypoxemia during brain development may mitigate disturbances in hippocampal maturation.

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Hypoxia and connectivity in the developing vertebrate nervous system

Cited by 22 publications

References 127 publications

Integrated Hypoxia Signaling and Oxidative Stress in Developmental Neurotoxicity of Benzo[a]Pyrene in Zebrafish Embryos

Integrated Hypoxia Signaling and Oxidative Stress in Developmental Neurotoxicity of Benzo[a]Pyrene in Zebrafish Embryos

Association of Iron-Deficiency Anemia and Non-Iron-Deficiency Anemia with Neurobehavioral Development in Children Aged 6–24 Months

Transient Hypoxemia Disrupts Anatomical and Functional Maturation of Preterm Fetal Ovine CA1 Pyramidal Neurons

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