Glucocorticosteroids Effects on Brain Development in the Preterm Infant: A Role for Microglia?

Zinni, Manuela; Pansiot, Julien; Billion, Elodie; Baud, Olivier; Mairesse, Jérôme

doi:10.2174/1570159x19666210517112913

Cited by 6 publications

(2 citation statements)

References 255 publications

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“…Since organoid culture media contains B-27 and extra insulin, we reasoned that adding more glucocorticoid with media replacement would set rhythms to around GCT 0-2 and improve rhythmic amplitude via enhanced synchronicity. We further hypothesised that the greatest phase shift would be achieved if glucocorticoid was applied at around GCT 12 (the most ‘incorrect’ biological time), but that this response may (a) take time to develop in culture and (b) depend on glucocorticoid type 49 . Accordingly, adding hydrocortisone at GCT 12 reduced the variability in period length of individual organoids, and increased the relative amplitude of rhythms beyond that achieved by ageing in culture alone ( Fig.3b, Extended Data Fig.4 ).…”

Section: Introductionmentioning

confidence: 99%

Circadian clocks in human cerebral organoids

Rzechorzek,

Sutcliffe,

Mihut

et al. 2024

Preprint

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SummaryCircadian rhythms result from cell-intrinsic timing mechanisms that impact health and disease1,2. To date, however, neural circadian research has largely focused on the hypothalamic circuitry of nocturnal rodents3. Whether circadian rhythms exist in human brain cells is unknown. Here we showbona fidecircadian rhythms in human neurons, glia, cerebral organoids, and cerebral organoid slices (ALI-COs)4–8. Human neural circadian rhythms are synchronised by physiological timing cues such as glucocorticoids and daily temperature cycles, and these rhythms are temperature-compensated across the range of normal human brain temperatures9. Astrocyte rhythms are phase-advanced relative to other cultures and they modulate neuronal clock responses to temperature shift. Cerebral organoid rhythms are more robust at physiological brain temperatures; the relative amplitude of these rhythms increases over time in culture and their resetting capacity recapitulates key neurodevelopmental transitions in glucocorticoid signalling10–14. Remarkably, organoid post-transcriptional bioluminescent clock reporter rhythms are retained even when those of their putative transcriptional drivers are indiscernible15, and electrophysiology recordings confirm circadian rhythms in functional activity of monocultures, organoids, and ALI-COs. Around one third of the cerebral organoid proteome and phosphoproteome are circadian-rhythmic, with temporal consolidation of disease-relevant neural processes. Finally, we show that human brain organoid rhythms can be modulated and disrupted by commonly used brain-permeant drugs and mistimed cortisol exposure, respectively. Our results demonstrate that human brain cells and tissues develop their own circadian oscillations and that canonical mechanisms of the circadian clockwork may be inadequate to explain these rhythmic phenomena. 2D and 3D human neural cultures represent complementary and tractable models for exploring the emergence, disruption, and mechanics of the circadian neural clockwork, with important implications for chronobiology, brain function, and brain health.

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Section: Introductionmentioning

confidence: 99%

Circadian clocks in human cerebral organoids

Rzechorzek,

Sutcliffe,

Mihut

et al. 2024

Preprint

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“…The neurological side effects of systemic steroids in premature infants are thought to be caused by interference with normal myelination processes as well as changes in neuronal connectivity, neurotransmitter systems, and neuronal growth factors in the developing brain [ 8 ]. While brain development continues beyond infancy and into early childhood [ 9 ], clinical data are lacking on the effects of systemic steroid use on neurodevelopment in full-term infants without underlying medical conditions.…”

Section: Introductionmentioning

confidence: 99%

Neurodevelopment in Term Infants with Normal Birthweight following Postnatal Systemic Steroid Exposure

Yi,

Ha,

Shin

et al. 2024

Neuroepidemiology

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Background: Studies investigating the potential impact of systemic steroid exposure during early infancy on neurological development in full-term infants with normal birth weight are lacking. Methods: This population-based administrative cohort study used data of national health insurance and a health-screening program for infants and children and included full-term infants who were born in Korea between 2008 and 2012 with normal birth weight and did not have any specific perinatal or neurodevelopmental diseases. The prescription of systemic steroids within the first 3 months of age was mainly considered. The neurological development of children was assessed using the Korean Development Screening Test (K-DST) at 6 years of age. To balance the baseline characteristics of the control and exposed groups, stabilized Inverse Probability of Treatment Weighting with trimming was performed in the main cohort. Ordinal logistic regression was used to assess the association between systemic steroid exposure and unfavorable results in the K-DST. Results: The control and exposure groups had 246,168 and 5,083 children, respectively. The K-DST suggested unfavorable results in 8.1% and 8.6% children in the control and exposure groups, respectively (weighted odds ratio [OR], 95% confidence interval [CI], 1.03, 0.93 – 1.14). When each domain of the K-DST was considered separately, the risk of unfavorable results in the exposed group was not significantly different from that in the control group. Conclusions: No significant association was observed between exposure to systemic steroids during early infancy and neurodevelopmental impairment at 6 years of age.

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Role of the gut-microbiota-metabolite-brain axis in the pathogenesis of preterm brain injury

Yang

Liu

et al. 2023

Biomedicine & Pharmacotherapy

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Glucocorticosteroids Effects on Brain Development in the Preterm Infant: A Role for Microglia?

Cited by 6 publications

References 255 publications

Circadian clocks in human cerebral organoids

Circadian clocks in human cerebral organoids

Neurodevelopment in Term Infants with Normal Birthweight following Postnatal Systemic Steroid Exposure

Role of the gut-microbiota-metabolite-brain axis in the pathogenesis of preterm brain injury

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