Developmental ethanol exposure has minimal impact on cerebellar microglial dynamics, morphology, and interactions with Purkinje cells during adolescence

Frontiers in Neuroscience

Neuroscience

Paul D. Drew¹  James C. Douglas¹  MaKenna Y. Cealie²  Ania K. Majewska²  Linh H. D. Le²  Erik D. Vonkaenel³  Matthew N. McCall³ 

[1] Drew Laboratory, Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, United States;Majewska Laboratory, Department of Neuroscience, School of Medicine and Dentistry, University of Rochester, Rochester, NY, United States;McCall Laboratory, Department of Biostatistics and Computational Biology, School of Medicine and Dentistry, University of Rochester, Rochester, NY, United States;

关键词: microglia;    cerebellum;    Purkinje cell;    immune system;    ethanol;    fetal alcohol spectrum disorders (FASD);    prenatal alcohol exposure;    neurodevelopment;   

DOI  :  10.3389/fnins.2023.1176581

 received in 2023-02-28, accepted in 2023-04-17,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionFetal alcohol spectrum disorders (FASD) are the most common cause of non-heritable, preventable mental disability, occurring in almost 5% of births in the United States. FASD lead to physical, behavioral, and cognitive impairments, including deficits related to the cerebellum. There is no known cure for FASD and their mechanisms remain poorly understood. To better understand these mechanisms, we examined the cerebellum on a cellular level by studying microglia, the principal immune cells of the central nervous system, and Purkinje cells, the sole output of the cerebellum. Both cell types have been shown to be affected in models of FASD, with increased cell death, immune activation of microglia, and altered firing in Purkinje cells. While ethanol administered in adulthood can acutely depress the dynamics of the microglial process arbor, it is unknown how developmental ethanol exposure impacts microglia dynamics and their interactions with Purkinje cells in the long term.MethodsTo address this question, we used a mouse model of human 3rd trimester exposure, whereby L7cre/Ai9+/−/Cx3cr1G/+ mice (with fluorescently labeled microglia and Purkinje cells) of both sexes were subcutaneously treated with a binge-level dose of ethanol (5.0 g/kg/day) or saline from postnatal days 4–9. Cranial windows were implanted in adolescent mice above the cerebellum to examine the long-term effects of developmental ethanol exposure on cerebellar microglia and Purkinje cell interactions using in vivo two-photon imaging.ResultsWe found that cerebellar microglia dynamics and morphology were not affected after developmental ethanol exposure. Microglia dynamics were also largely unaltered with respect to how they interact with Purkinje cells, although subtle changes in these interactions were observed in females in the molecular layer of the cerebellum.DiscussionThis work suggests that there are limited in vivo long-term effects of ethanol exposure on microglia morphology, dynamics, and neuronal interactions, so other avenues of research may be important in elucidating the mechanisms of FASD.

【 授权许可】

Unknown   
Copyright © 2023 Cealie, Douglas, Le, Vonkaenel, McCall, Drew and Majewska.