Neonatal Hyperoxia Perturbs Neuronal Development in the Cerebellum

Scheuer, Till; Sharkovska, Yuliya; Tarabykin, Victor; Marggraf, Katharina; Brockmöller, Vivien; Bührer, Christoph; Endesfelder, Stefanie; Schmitz, Thomas

doi:10.1007/s12035-017-0612-5

Cited by 30 publications

(30 citation statements)

References 91 publications

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“…The protection of cerebellar white matter development by minocycline was associated with improved PDGF-A expression in vivo and in astrocyte cultures in vitro, underlining a role for astroglial PDGF-A both in injury and protection in the cerebellum. Administration of PDGF-A intranasally after exposure to oxygen challenge moreover resulted in enhanced proliferation of oligodendroglial lineage cells in the cerebellar white matter [134], hence strengthening the view of growth factor synthesis as a target for protective treatment after postnatal insult.…”

Section: Growth Factorsmentioning

confidence: 80%

Glial Factors Regulating White Matter Development and Pathologies of the Cerebellum

et al. 2020

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The cerebellum is a brain region that undergoes extremely dynamic growth during perinatal and postnatal development which is regulated by the proper interaction between glial cells and neurons with a complex concert of growth factors, chemokines, cytokines, neurotransmitters and transcriptions factors. The relevance of cerebellar functions for not only motor performance but also for cognition, emotion, memory and attention is increasingly being recognized and acknowledged. Since perturbed circuitry of cerebro-cerebellar trajectories can play a role in many central nervous system pathologies and thereby contribute to neurological symptoms in distinct neurodevelopmental and neurodegenerative diseases, is it the aim with this mini-review to highlight the pathways of glia-glia interplay being involved. The designs of future treatment strategies may hence be targeted to molecular pathways also playing a role in development and disease of the cerebellum.

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Section: Growth Factorsmentioning

confidence: 80%

Glial Factors Regulating White Matter Development and Pathologies of the Cerebellum

et al. 2020

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“…Furthermore, since proteomic and bioenergetic studies were done from the whole hippocampus, it is not possible to determine whether these oxygen-induced proteomic and mitochondrial functional changes were predominantly derived from neurons or glial cells or a combination of both. In this study, we focused on proteomics and mitochondrial bioenergetics only from the hippocampal homogenates, and not from regions such as cerebellum, amygdala, corpus callosum, and white matter tracts which may also are impacted by hyperoxia exposure [21][22][23] . Even though hippocampal complexes I and IV activities were measured, complex III and complex V activities were not measured due to technical difficulties and the size of the hippocampus.…”

Section: Discussionmentioning

confidence: 99%

Early Life Supraphysiological Levels of Oxygen Exposure Permanently Impairs Hippocampal Mitochondrial Function

Ramani

Miller

Kumar

et al. 2019

Preprint

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Preterm infants requiring prolonged oxygen therapy often develop cognitive dysfunction later life. Previously, we reported that 14-week-old young adult mice exposed to hyperoxia as newborns had spatial memory deficits and hippocampal shrinkage. We hypothesized that the underlying mechanism was the induction of hippocampal mitochondrial dysfunction by neonatal hyperoxia. C57BL/6j mouse pups were exposed to 85% oxygen or air from P2 -P14.Hippocampal proteomic analysis was performed in young adult mice (14 weeks). Mitochondrial bioenergetics were measured in neonatal (P14) and young adult mice. We found that hyperoxia exposure reduced mitochondrial ATP-linked oxygen consumption and increased state 4 respiration linked proton leak in both neonatal and young adult mice. Following hyperoxia exposure, complex I function was decreased at P14 but increased in young adult mice. Proteomic analysis revealed that neonatal hyperoxia exposure decreased complex I NDUFB8 and NDUFB11 and complex IV 7B subunits, but increased complex III subunit 9 in young adult mice. In conclusion, neonatal hyperoxia permanently impairs hippocampal mitochondrial function and alters complex I function. These changes may account for memory deficits seen in preterm survivors following prolonged oxygen supplementation and may potentially be a contributing mechanism in other oxidative stress associated cognitive disorders.

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“…These morphological changes were most prominent at P0 and P2, coinciding in time with the finding of decreased EGL proliferation. The vulnerability of Purkinje cell development to insults associated with preterm birth have been recently shown in rat pups exposed to neonatal hyperoxia and also in preterm rabbit pups with preterm cerebral intraventricular hemorrhage exhibiting delayed maturation of Purkinje cells and decreased granular precursor cell proliferation [26, 27]. The cerebellar Purkinje cells have several key functions relating to EGL proliferation, and subsequent inward cell migration and Purkinje cell secretion of the transcription factor Shh are key for EGL precursor cell proliferation [12, 13, 28].…”

Section: Discussionmentioning

confidence: 99%

Impaired Cerebellar Maturation, Growth Restriction, and Circulating Insulin-Like Growth Factor 1 in Preterm Rabbit Pups

Sveinsdóttir

Länsberg²,

Sveinsdóttir³

et al. 2017

Dev Neurosci

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Cerebellar growth is impeded following very preterm birth in human infants and the observed reduction in cerebellar volume is associated with neurodevelopmental impairment. Decreased levels of circulating insulin-like growth factor 1 (IGF-1) are associated with decreased cerebellar volume. The relationship between preterm birth, circulating IGF-1, and key cell populations supporting cerebellar proliferation is unknown. The aim of this study was to evaluate the effect of preterm birth on postnatal growth, circulating IGF-1, and cerebellar maturation in a preterm rabbit pup model. Preterm rabbit pups (PT) were delivered by cesarean section at day 29 of gestation, cared for in closed incubators with humidified air, and gavage fed with formula. Control term pups (T) delivered by spontaneous vaginal delivery at day 32 of gestation were housed and fed by their lactating doe. In vivo perfusion-fixation for immunohistochemical evaluation of cerebellar proliferation, cell maturation, and apoptosis was performed at repeated time points in PT and T pups. Results show that the mean weight of the pups and circulating IGF-1 protein levels were lower in the PT group at all time points (p < 0.05) than in the T group. Postnatal weight development correlated with circulating IGF-1 (r² = 0.89) independently of gestational age at birth and postnatal age. The proliferative (Ki-67-positive) portion of the external granular layer (EGL) was decreased in the PT group at postnatal day 2 (P2) compared to in the T group (p = 0.01). Purkinje cells exhibited decreased calbindin staining at P0 (p = 0.003), P2 (p = 0.004), and P5 (p = 0.04) in the PT group compared to in the T group. Staining for sonic hedgehog was positive in neuronal EGL progenitors and Purkinje cells at early time points but was restricted to a well-defined Purkinje cell monolayer at later time points. Preterm birth in rabbit pups is associated with lower circulating levels of IGF-1, decreased postnatal growth, and decreased cerebellar EGL proliferation and Purkinje cell maturation. The preterm rabbit pup model exhibits important characteristics of human preterm birth, and may thus be suitable for the evaluation of interventions aiming to modify growth and cerebellar development in the preterm population.

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Neonatal Hyperoxia Perturbs Neuronal Development in the Cerebellum

Cited by 30 publications

References 91 publications

Glial Factors Regulating White Matter Development and Pathologies of the Cerebellum

Glial Factors Regulating White Matter Development and Pathologies of the Cerebellum

Early Life Supraphysiological Levels of Oxygen Exposure Permanently Impairs Hippocampal Mitochondrial Function

Impaired Cerebellar Maturation, Growth Restriction, and Circulating Insulin-Like Growth Factor 1 in Preterm Rabbit Pups

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