Early life psychosocial stress increases binge-like ethanol consumption and CSF1R inhibition prevents stress-induced alterations in microglia and brain macrophage population density
Early life stress (ELS) has lasting consequences on microglia and brain macrophage function. During ELS, microglia and brain macrophages alter their engagement with synapses leading to changes in neuronal excitability. Further, ELS can induce innate immune memory formation in microglia and brain mac...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | Brain, Behavior, & Immunity - Health |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666354624002114 |
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| author | Stephen C. Gironda Samuel W. Centanni Jeffrey L. Weiner |
| author_facet | Stephen C. Gironda Samuel W. Centanni Jeffrey L. Weiner |
| author_sort | Stephen C. Gironda |
| collection | DOAJ |
| description | Early life stress (ELS) has lasting consequences on microglia and brain macrophage function. During ELS, microglia and brain macrophages alter their engagement with synapses leading to changes in neuronal excitability. Further, ELS can induce innate immune memory formation in microglia and brain macrophages resulting in altered responsivity to future environmental stimuli. These alterations can result in lasting adaptations in circuit function and may mediate the relationship between ELS and the risk to develop alcohol use disorder (AUD). Whether microglia and brain macrophages truly mediate this relationship remains elusive. Here, we report: 1) an ELS model, psychosocial stress (PSS), increases binge-like ethanol consumption in early adulthood. 2) Repeated binge-like ethanol consumption increases microglia and brain macrophage population densities across the brain. 3) PSS may elicit innate immune memory formation in microglia and brain macrophages leading to altered population densities following repeated binge-like ethanol consumption. 4) Microglia and brain macrophage inhibition trended towards preventing PSS-evoked changes in binge-like ethanol consumption and normalized microglia and brain macrophage population densities. Therefore, our study suggests that acutely inhibiting microglia and brain macrophage function during periods of early life PSS may prevent innate immune memory formation and assist in reducing the risk to develop AUD. |
| format | Article |
| id | doaj-art-e1ff2ea637264f1881718c41d950513d |
| institution | Kabale University |
| issn | 2666-3546 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain, Behavior, & Immunity - Health |
| spelling | doaj-art-e1ff2ea637264f1881718c41d950513d2025-01-26T05:05:03ZengElsevierBrain, Behavior, & Immunity - Health2666-35462025-02-0143100933Early life psychosocial stress increases binge-like ethanol consumption and CSF1R inhibition prevents stress-induced alterations in microglia and brain macrophage population densityStephen C. Gironda0Samuel W. Centanni1Jeffrey L. Weiner2Corresponding author.; Department of Translational Neuroscience, Wake Forest University School of Medicine, Winston Salem, NC, 27101, USADepartment of Translational Neuroscience, Wake Forest University School of Medicine, Winston Salem, NC, 27101, USACorresponding author.; Department of Translational Neuroscience, Wake Forest University School of Medicine, Winston Salem, NC, 27101, USAEarly life stress (ELS) has lasting consequences on microglia and brain macrophage function. During ELS, microglia and brain macrophages alter their engagement with synapses leading to changes in neuronal excitability. Further, ELS can induce innate immune memory formation in microglia and brain macrophages resulting in altered responsivity to future environmental stimuli. These alterations can result in lasting adaptations in circuit function and may mediate the relationship between ELS and the risk to develop alcohol use disorder (AUD). Whether microglia and brain macrophages truly mediate this relationship remains elusive. Here, we report: 1) an ELS model, psychosocial stress (PSS), increases binge-like ethanol consumption in early adulthood. 2) Repeated binge-like ethanol consumption increases microglia and brain macrophage population densities across the brain. 3) PSS may elicit innate immune memory formation in microglia and brain macrophages leading to altered population densities following repeated binge-like ethanol consumption. 4) Microglia and brain macrophage inhibition trended towards preventing PSS-evoked changes in binge-like ethanol consumption and normalized microglia and brain macrophage population densities. Therefore, our study suggests that acutely inhibiting microglia and brain macrophage function during periods of early life PSS may prevent innate immune memory formation and assist in reducing the risk to develop AUD.http://www.sciencedirect.com/science/article/pii/S2666354624002114Early life stressAlcoholMicrogliaLight-Sheet Fluorescence MicroscopyCSF1R inhibitionMacrophage |
| spellingShingle | Stephen C. Gironda Samuel W. Centanni Jeffrey L. Weiner Early life psychosocial stress increases binge-like ethanol consumption and CSF1R inhibition prevents stress-induced alterations in microglia and brain macrophage population density Brain, Behavior, & Immunity - Health Early life stress Alcohol Microglia Light-Sheet Fluorescence Microscopy CSF1R inhibition Macrophage |
| title | Early life psychosocial stress increases binge-like ethanol consumption and CSF1R inhibition prevents stress-induced alterations in microglia and brain macrophage population density |
| title_full | Early life psychosocial stress increases binge-like ethanol consumption and CSF1R inhibition prevents stress-induced alterations in microglia and brain macrophage population density |
| title_fullStr | Early life psychosocial stress increases binge-like ethanol consumption and CSF1R inhibition prevents stress-induced alterations in microglia and brain macrophage population density |
| title_full_unstemmed | Early life psychosocial stress increases binge-like ethanol consumption and CSF1R inhibition prevents stress-induced alterations in microglia and brain macrophage population density |
| title_short | Early life psychosocial stress increases binge-like ethanol consumption and CSF1R inhibition prevents stress-induced alterations in microglia and brain macrophage population density |
| title_sort | early life psychosocial stress increases binge like ethanol consumption and csf1r inhibition prevents stress induced alterations in microglia and brain macrophage population density |
| topic | Early life stress Alcohol Microglia Light-Sheet Fluorescence Microscopy CSF1R inhibition Macrophage |
| url | http://www.sciencedirect.com/science/article/pii/S2666354624002114 |
| work_keys_str_mv | AT stephencgironda earlylifepsychosocialstressincreasesbingelikeethanolconsumptionandcsf1rinhibitionpreventsstressinducedalterationsinmicrogliaandbrainmacrophagepopulationdensity AT samuelwcentanni earlylifepsychosocialstressincreasesbingelikeethanolconsumptionandcsf1rinhibitionpreventsstressinducedalterationsinmicrogliaandbrainmacrophagepopulationdensity AT jeffreylweiner earlylifepsychosocialstressincreasesbingelikeethanolconsumptionandcsf1rinhibitionpreventsstressinducedalterationsinmicrogliaandbrainmacrophagepopulationdensity |