Microglia and Sensitive Periods in Brain Development

Dziabis, Julia E.; Bilbo, Staci D.

doi:10.1007/7854_2021_242

Cited by 17 publications

(16 citation statements)

References 134 publications

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“…Microglia colonize the CNS early during embryogenesis and contribute to various developmental processes. The early roles of embryonic microglia have only begun to be described in rodents, including the regulation of axonal tract formation (Pont-Lezica et al, 2014; Squarzoni et al, 2014), positioning of migratory interneurons (Squarzoni et al, 2014), modulation of neurogenesis and synapse refinement (for review see (Dziabis and Bilbo, 2021). Thus, microglia are implicated in a wide range of processes, rendering these cells important contributors to the assembly and refinement of central neuronal circuits during ontogenesis.…”

Section: Discussionmentioning

confidence: 99%

Microglia shape the embryonic development of mammalian respiratory networks

Cabirol

Cardoit

Courtand

et al. 2022

Preprint

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Microglia, brain-resident macrophages, play key roles during prenatal development in defining neural circuitry function, including ensuring proper synaptic wiring and maintaining homeostasis. Mammalian breathing rhythmogenesis arises from interacting brainstem neural networks that are assembled during embryonic development, but the specific role of microglia in this process remains unknown. Here, we investigated the anatomical and functional consequences of respiratory circuit formation in the absence of microglia. We first established the normal distribution of microglia within the wild-type (WT, Pu.1+/+) mouse brainstem at embryonic ages when the respiratory networks are known to emerge (embryonic day (E) 14.5 for the parafacial respiratory group (epF) and E16.5 for the preBötzinger complex (preBötC)). In transgenic mice depleted of microglia (Pu.1-/- mutant), we performed anatomical staining, calcium imaging and electrophysiological recordings of neuronal activities in vitro to assess the status of these circuits at their respective times of functional emergence. Spontaneous respiratory-related activity recorded from reduced in vitro preparations showed an abnormally slow rhythm frequency expressed by the epF at E14.5, the preBötC at E16.5 and in the phrenic motor nerves from E16.5 onwards. These deficits were associated with a reduced number of active epF neurons, defects in commissural projections that couple the bilateral preBötC half-centers, and an accompanying decrease in their functional coordination. These abnormalities probably contribute to eventual neonatal death, since plethysmography revealed that E18.5 Pu.1-/- embryos are unable to sustain breathing activity ex utero. Our results thus point to a crucial contribution of microglia in the proper establishment of the central respiratory command during embryonic development.

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Section: Discussionmentioning

confidence: 99%

Microglia shape the embryonic development of mammalian respiratory networks

Cabirol

Cardoit

Courtand

et al. 2022

Preprint

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“…In recent decades, there has been increasing interest in understanding the importance of commensal bacteria as a major environmental component that promotes healthy development, and is not only related to infectious diseases [ 127 ]. The gut microbiota is essential in shaping the development of both the immune and the nervous system [ 129 ] through a symbiotic interaction with the host [ 130 ], providing environmental “clues” that influence immune system development, including pathogen-associated molecular patterns (PAMPs), such as LPS, MDP-2 (muramyl dipeptide 2) and LPA (lysophosphatidic acid), that activate mucosal TLRs, which drive immune system development [ 131 , 132 , 133 ]. Indeed, it has been proposed that newborns present a reduced immunological response compared to adults because their gut may be sterile during gestation, and therefore “naïve” to pathogens [ 134 ].…”

Section: Lactoferrin and The Development Of Infant Microbiomementioning

confidence: 99%

“…Moreover, GF mice present abnormal behavior [ 135 , 136 ], immature microglia [ 130 , 137 , 138 ] and abnormal intestine sizes. Since microglia are responsible for synaptic pruning during brain maturation, such hypofunction has been linked to future psychiatric diseases [ 131 , 132 , 133 ]. The gut microbiome also provides the host with metabolites which would otherwise be unavailable, such as short-chain fatty acids (SCFA) (e.g., butyrate, propionate and acetate) [ 139 ].…”

Section: Lactoferrin and The Development Of Infant Microbiomementioning

confidence: 99%

Neuroprotective Role of Lactoferrin during Early Brain Development and Injury through Lifespan

2022

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Early adverse fetal environments can significantly disturb central nervous system (CNS) development and subsequently alter brain maturation. Nutritional status is a major variable to be considered during development and increasing evidence links neonate and preterm infant impaired brain growth with neurological and psychiatric diseases in adulthood. Breastfeeding is one of the main components required for healthy newborn development due to the many “constitutive” elements breastmilk contains. Maternal intake of specific nutrients during lactation may alter milk composition, thus affecting newborn nutrition and, potentially, brain development. Lactoferrin (Lf) is a major protein present in colostrum and the main protein in human milk, which plays an important role in the benefits of breastfeeding during postnatal development. It has been demonstrated that Lf has antimicrobial, as well as anti-inflammatory properties, and is potentially able to reduce the incidence of sepsis and necrotizing enterocolitis (NEC), which are particularly frequent in premature births. The anti-inflammatory effects of Lf can reduce birth-related pathologies by decreasing the release of pro-inflammatory factors and inhibiting premature cervix maturation (also related to commensal microbiome abnormalities) that could contribute to disrupting brain development. Pre-clinical evidence shows that Lf protects the developing brain from neuronal injury, enhances brain connectivity and neurotrophin production, and decreases inflammation in models of perinatal inflammatory challenge, intrauterine growth restriction (IUGR) and neonatal hypoxia-ischemia (HI). In this context, Lf can provide nutritional support for brain development and cognition and prevent the origin of neuropsychiatric diseases later in life. In this narrative review, we consider the role of certain nutrients during neurodevelopment linking to the latest research on lactoferrin with respect to neonatology. We also discuss new evidence indicating that early neuroprotective pathways modulated by Lf could prevent neurodegeneration through anti-inflammatory and immunomodulatory processes.

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“…Another additional aspect, potentially contributing to the consequence of eLA onto developmental process, is the involvement of multi-systemic inflammation and oxidative stress, two interconnected factors that have gained central attention in neuropsychiatric research over the past decade (Schafer and Stevens, 2010;Sekar et al, 2016;Devlin et al, 2021;Dziabis and Bilbo, 2021). On the one hand, the involvement of the immune system has been extensively described in a variety of brain disorders (Aw et al, 2021).…”

Section: Early-life Experience Shapes the Brain During Critical Perio...mentioning

confidence: 99%

At the Crossroad Between Resiliency and Fragility: A Neurodevelopmental Perspective on Early-Life Experiences

Chelini

Pangrazzi

Bozzi

2022

Front. Cell. Neurosci.

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Postnatal development of the brain is characterized by sensitive windows during which, local circuitry are drastically reshaped by life experiences. These critical periods (CPs) occur at different time points for different brain functions, presenting redundant physiological changes in the underlying brain regions. Although circuits malleability during CPs provides a valuable window of opportunity for adaptive fine-tuning to the living environment, this aspect of neurodevelopment also represents a phase of increased vulnerability for the development of a variety of disorders. Consistently, accumulating epidemiological studies point to adverse childhood experience as a major risk factor for many medical conditions, especially stress- and anxiety-related conditions. Thanks to creative approaches to manipulate rodents’ rearing environment, neurobiologist have uncovered a pivotal interaction between CPs and early-life experiences, offering an interesting landscape to improve our understanding of brain disorders. In this short review, we discuss how early-life experience impacts cellular and molecular players involved in CPs of development, translating into long-lasting behavioral consequences in rodents. Bringing together findings from multiple laboratories, we delineate a unifying theory in which systemic factors dynamically target the maturation of brain functions based on adaptive needs, shifting the balance between resilience and vulnerability in response to the quality of the rearing environment.

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Microglia and Sensitive Periods in Brain Development

Cited by 17 publications

References 134 publications

Microglia shape the embryonic development of mammalian respiratory networks

Microglia shape the embryonic development of mammalian respiratory networks

Neuroprotective Role of Lactoferrin during Early Brain Development and Injury through Lifespan

At the Crossroad Between Resiliency and Fragility: A Neurodevelopmental Perspective on Early-Life Experiences

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