The Impact of Mouse Preterm Birth Induction by RU-486 on Microglial Activation and Subsequent Hypomyelination

Morin, Cécile; Guenoun, David; Sautet, Irvin; Faivre, Valérie; Schwendimann, Leslie; Young-Ten, Pierrette; Steenwinckel, Juliette Van; Gressèns, Pierre; Bokobza, Cindy

doi:10.3390/ijms23094867

Cited by 3 publications

(9 citation statements)

References 62 publications

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“…One potential bias in assessing the effects of C-section+PBS was that the present study focused on parameters that we previously showed to be altered in the V-delivery+IL-1b group [16,[29][30][31][32]44]. Other non-studied parameters could potentially have been altered in the C-section+PBS group.…”

Section: Discussionmentioning

confidence: 93%

“…We next quantified the PDGFRα + , PDGFRα + /O4 + , and O4 + cell populations by FACS [44] at P5 (Fig. 3A-B).…”

Section: Resultsmentioning

confidence: 99%

“…Similarly, social impairment is often associated with NDDs [47]. We used a previously described early developmental stage social behavioral test based on nest odor affinity to assess social impairment [29, 44]. At P8, pups exposed to perinatal inflammation spent less time on the nest sawdust (p=0.014; Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The C-section+PBS group showed few alterations, except for diversity of the gut microbiota, the density of PDGFRα + and PDGFRα + /O4 + cells, the number of USV calls, and brain connectivity. One potential bias in assessing the effects of C-section+PBS was that the present study focused on parameters that we previously showed to be altered in the V-delivery+IL-1β group [16, 29–32, 44]. Other non-studied parameters could potentially have been altered in the C-section+PBS group.…”

Section: Discussionmentioning

confidence: 96%

“…We further characterized the microglia and infiltrating macrophages in the present model using a previously published gating strategy [44] by quantifying the microglia, defined as CD11B + CD45 low cells, and infiltrating macrophages, defined as CD11B + CD45 high cells, at P5 (Fig. 2C).…”

Section: Impact Of C-section and Systemic Inflammation On Microglial ...mentioning

confidence: 99%

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C-section and systemic inflammation synergize to disrupt the neonatal gut microbiota and brain development in a model of prematurity

Morin,

Faure,

Guenoun

et al. 2023

Preprint

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Infants born very preterm (below 28 weeks of gestation) are at high risk of developing neurodevelopmental disorders, such as intellectual deficiency, autism spectrum disorders, and attention deficit. Preterm birth often occurs in the context of perinatal systemic inflammation due to chorioamnionitis and postnatal sepsis (Dammann, O. and Leviton, A., Intermittent or sustained systemic inflammation and the preterm brain. Pediatr Res, 2014. 75(3): p. 376-80). In addition, C-section is often performed for very preterm neonates to avoid hypoxia during a vaginal delivery (Luca, A.,et al., Birth trauma in preterm spontaneous vaginal and cesarean section deliveries: A 10-years retrospective study. PloS one,2022, 17(10), e0275726.) We have developed and characterized a mouse model based on intraperitoneal injections of IL-1b; between postnatal days one and five to reproduce perinatal systemic inflammation (Favrais, G.,et al., Systemic inflammation disrupts the developmental program of white matter. Ann Neurol,2011. 70(4): p. 550-65). This model replicates several neuropathological, brain imaging, and behavioral deficits observed in preterm infants. We hypothesized that C-sections could synergize with systemic inflammation to induce more severe brain abnormalities. We observed that C-sections significantly exacerbated the deleterious effects of IL-1b; on reduced gut microbial diversity, increased levels of circulating peptidoglycans, abnormal microglia/macrophage reactivity, impaired myelination, and reduced functional connectivity in the brain relative to vaginal delivery plus intraperitoneal saline. These data demonstrate the deleterious synergistic effects of C-section and neonatal systemic inflammation on brain maldevelopment and malfunction, two conditions frequently observed in very preterm infants, who are at high risk of developing neurodevelopmental disorders.

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Section: Discussionmentioning

confidence: 93%

“…We next quantified the PDGFRα + , PDGFRα + /O4 + , and O4 + cell populations by FACS [44] at P5 (Fig. 3A-B).…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 96%

Section: Impact Of C-section and Systemic Inflammation On Microglial ...mentioning

confidence: 99%

See 3 more Smart Citations

C-section and systemic inflammation synergize to disrupt the neonatal gut microbiota and brain development in a model of prematurity

Morin,

Faure,

Guenoun

et al. 2023

Preprint

Self Cite

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Key roles of glial cells in the encephalopathy of prematurity

Van Steenwinckel,

Bokobza,

Laforge

et al. 2023

Glia

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Across the globe, approximately one in 10 babies are born preterm, that is, before 37 weeks of a typical 40 weeks of gestation. Up to 50% of preterm born infants develop brain injury, encephalopathy of prematurity (EoP), that substantially increases their risk for developing lifelong defects in motor skills and domains of learning, memory, emotional regulation, and cognition. We are still severely limited in our abilities to prevent or predict preterm birth. No longer just the “support cells,” we now clearly understand that during development glia are key for building a healthy brain. Glial dysfunction is a hallmark of EoP, notably, microgliosis, astrogliosis, and oligodendrocyte injury. Our knowledge of glial biology during development is exponentially expanding but hasn't developed sufficiently for development of effective neuroregenerative therapies. This review summarizes the current state of knowledge for the roles of glia in infants with EoP and its animal models, and a description of known glial‐cell interactions in the context of EoP, such as the roles for border‐associated macrophages. The field of perinatal medicine is relatively small but has worked passionately to improve our understanding of the etiology of EoP coupled with detailed mechanistic studies of pre‐clinical and human cohorts. A primary finding from this review is that expanding our collaborations with computational biologists, working together to understand the complexity of glial subtypes, glial maturation, and the impacts of EoP in the short and long term will be key to the design of therapies that improve outcomes.

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Mice born preterm develop gait dystonia and reduced cortical parvalbumin immunoreactivity

Gemperli,

Folorunso,

Norin

et al. 2024

Preprint

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Preterm birth leading to cerebral palsy (CP) is the most common cause of childhood dystonia, a movement disorder that is debilitating and often treatment refractory. Dystonia has been typically associated with dysfunction of striatal cholinergic interneurons, but clinical imaging data suggests that cortical injury may best predict dystonia following preterm birth. Furthermore, abnormal sensorimotor cortex inhibition has been found in many studies of non-CP dystonias. To assess the potential for a cortical etiology of dystonia following preterm birth, we developed a new model of preterm birth in mice. Noting that term delivery in mice on a C57BL/6J background is embryonic day 19.1 (E19.1), we induced preterm birth at the limits of pup viability at embryonic day (E) 18.3, equivalent to human 22 weeks gestation. Mice born preterm demonstrate display clinically validated metrics of dystonia during gait (leg adduction amplitude and variability) and also demonstrate reduced parvalbumin immunoreactivity in the sensorimotor cortex, suggesting dysfunction of cortical parvalbumin-positive inhibitory interneurons. Notably, reduced parvalbumin immunoreactivity or changes in parvalbumin-positive neuronal number were not observed in the striatum. These data support the association between cortical dysfunction and dystonia following preterm birth. We propose that our mouse model of preterm birth can be used to study this association and potentially also study other sequelae of extreme prematurity.

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The Impact of Mouse Preterm Birth Induction by RU-486 on Microglial Activation and Subsequent Hypomyelination

Cited by 3 publications

References 62 publications

C-section and systemic inflammation synergize to disrupt the neonatal gut microbiota and brain development in a model of prematurity

C-section and systemic inflammation synergize to disrupt the neonatal gut microbiota and brain development in a model of prematurity

Key roles of glial cells in the encephalopathy of prematurity

Mice born preterm develop gait dystonia and reduced cortical parvalbumin immunoreactivity

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