Microglia and astrocytes show limited, acute alterations in morphology and protein expression following a single developmental alcohol exposure

Lowery, Rebecca L.; Cealie, MaKenna; Lamantia, Cassandra E.; Mendes, Monique; Drew, Paul D.; Majewska, Ania K.

doi:10.1002/jnr.24808

Cited by 10 publications

(12 citation statements)

References 63 publications

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“…This is in part due to a lack of understanding of the molecular mechanisms that underlie the widespread symptoms seen in patients. Previous studies have shown that microglia in the somatosensory cortex are sensitive to even a single binge‐level EtOH exposure during the BGS (Ahlers et al., 2015; Lowery et al., 2021). Here, we wanted to determine if a more prolonged BGS exposure could alter microglial dynamics in the long‐term, changing their ability to interact with dendrites and thereby impacting the stability and remodeling of dendritic spines, which have been shown to be a target for EtOH in development.…”

Section: Discussionmentioning

confidence: 99%

“…This suggested that EtOH could affect synaptic plasticity through nonmicroglial pathways, despite the known roles of microglia in sculpting neuronal networks in development and adulthood. Additionally, we have recently described changes in microglial morphology in the somatosensory cortex after even a single dose of EtOH during the BGS (Lowery et al, 2021). However, we had not tried to image the physical interactions that microglia make with dendritic spines, allowing the possibility that although microglial dynamics were not altered on a gross level, the targeted recruitment of microglia to dendritic spines may have been disrupted, resulting in changes in synaptic remodeling.…”

Section: 3mentioning

confidence: 99%

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Dynamics of microglia and dendritic spines in early adolescent cortex after developmental alcohol exposure

Wong

Strohm

Atlas

et al. 2021

Developmental Neurobiology

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Fetal alcohol spectrum disorder patients suffer from many cognitive disabilities. These include impaired auditory, visual, and tactile sensory information processing, making it more difficult for these patients to learn to navigate social scenarios. Rodent studies have shown that alcohol exposure during the brain growth spurt (BGS) can lead to acute neuronal apoptosis and an immunological response by microglia in the somatosensory cortex. Since microglia have critical physiological functions, including the support of excitatory synapse remodeling via interactions with dendritic spines, we sought to understand whether BGS alcohol exposure has long‐term effects on microglial or dendritic spine dynamics. Using in vivo two‐photon microscopy in 4–5 week old mice, we evaluated microglial functions such as process motility, the response to tissue injury, and the dynamics of physical interactions between microglial processes and dendritic spines. We also investigated potential differences in the morphology, density, or dynamics of dendritic spines in layer I/II primary sensory cortex of control and BGS alcohol exposed mice. We found that microglial process motility and contact with dendritic spines were not altered after BGS alcohol exposure. While the response of microglial processes toward tissue injury was not significantly altered by prior alcohol exposure, there was a trend suggesting that alcohol early in life may prime microglia to respond more quickly to secondary injury. Spine density, morphology, stability, and remodeling over time were not perturbed after BGS alcohol exposure. We demonstrate that after BGS alcohol exposure, the physiological functions of microglia and excitatory neurons remain intact in early adolescence.

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Section: Discussionmentioning

confidence: 99%

Section: 3mentioning

confidence: 99%

Dynamics of microglia and dendritic spines in early adolescent cortex after developmental alcohol exposure

Wong

Strohm

Atlas

et al. 2021

Developmental Neurobiology

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“…Confocal z-stacks were collected with a 40× objective and z-step of 0.3 μm to examine microglia arbor complexity for each section with Sholl analysis as described in [ 34 , 37 , 38 ]. Microglia were excluded if their entire process arbor was not contained in the XY-axes or their entire cell body was not contained in the Z-axis.…”

Section: Methodsmentioning

confidence: 99%

Developmental Ethanol Exposure Impacts Purkinje Cells but Not Microglia in the Young Adult Cerebellum

Cealie,

Douglas,

Swan

et al. 2024

Cells

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Fetal alcohol spectrum disorders (FASD) caused by developmental ethanol exposure lead to cerebellar impairments, including motor problems, decreased cerebellar weight, and cell death. Alterations in the sole output of the cerebellar cortex, Purkinje cells, and central nervous system immune cells, microglia, have been reported in animal models of FASD. To determine how developmental ethanol exposure affects adult cerebellar microglia and Purkinje cells, we used a human third-trimester binge exposure model in which mice received ethanol or saline from postnatal (P) days 4–9. In adolescence, cerebellar cranial windows were implanted and mice were aged to young adulthood for examination of microglia and Purkinje cells in vivo with two-photon imaging or in fixed tissue. Ethanol had no effect on microglia density, morphology, dynamics, or injury response. However, Purkinje cell linear frequency was reduced by ethanol. Microglia–Purkinje cell interactions in the Purkinje Cell Layer were altered in females compared to males. Overall, developmental ethanol exposure had few effects on cerebellar microglia in young adulthood and Purkinje cells appeared to be more susceptible to its effects.

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“…Foetal alcohol syndrome (FAS) is one of the most severe types of FASD [ 2 ]. Many aspects of FASD disorder have been successfully summarised in vitro and in vivo, including morphological and behavioural defects, but the pathogenesis of the disease is still unclear [ 3 , 4 ]. The unawareness of pregnancy or addictive alcoholism in women during pregnancy has led to FASD in recent years.…”

Section: Introductionmentioning

confidence: 99%

ERK1/2 Signalling Pathway Regulates Tubulin-Binding Cofactor B Expression and Affects Astrocyte Process Formation after Acute Foetal Alcohol Exposure

et al. 2022

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Foetal alcohol spectrum disorders (FASDs) are a spectrum of neurological disorders whose neurological symptoms, besides the neuronal damage caused by alcohol, may also be associated with neuroglial damage. Tubulin-binding cofactor B (TBCB) may be involved in the pathogenesis of FASD. To understand the mechanism and provide new insights into the pathogenesis of FASD, acute foetal alcohol exposure model on astrocytes was established and the interference experiments were carried out. First, after alcohol exposure, the nascent astrocyte processes were reduced or lost, accompanied by the absence of TBCB expression and the disruption of microtubules (MTs) in processes. Subsequently, TBCB was silenced with siRNA. It was severely reduced or lost in nascent astrocyte processes, with a dramatic reduction in astrocyte processes, indicating that TBCB plays a vital role in astrocyte process formation. Finally, the regulating mechanism was studied and it was found that the extracellular signal-regulated protease 1/2 (ERK1/2) signalling pathway was one of the main pathways regulating TBCB expression in astrocytes after alcohol injury. In summary, after acute foetal alcohol exposure, the decreased TBCB in nascent astrocyte processes, regulated by the ERK1/2 signalling pathway, was the main factor leading to the disorder of astrocyte process formation, which could contribute to the neurological symptoms of FASD.

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Microglia and astrocytes show limited, acute alterations in morphology and protein expression following a single developmental alcohol exposure

Cited by 10 publications

References 63 publications

Dynamics of microglia and dendritic spines in early adolescent cortex after developmental alcohol exposure

Dynamics of microglia and dendritic spines in early adolescent cortex after developmental alcohol exposure

Developmental Ethanol Exposure Impacts Purkinje Cells but Not Microglia in the Young Adult Cerebellum

ERK1/2 Signalling Pathway Regulates Tubulin-Binding Cofactor B Expression and Affects Astrocyte Process Formation after Acute Foetal Alcohol Exposure

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