Sex differences in the neuroimmune response following heavy, binge-like alcohol exposure in adolescent rats

IF 2.5 4区医学 Q3 IMMUNOLOGY

Journal of neuroimmunology Pub Date : 2025-09-02 DOI:10.1016/j.jneuroim.2025.578742

Catherine E. Van Doorn , Natalie Nawarawong , Deann M. Hopkins , Hui Peng , James R. Pauly , Kimberly Nixon

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Abstract

Adolescents who consume alcohol show a high prevalence of binge drinking, which has been linked to brain damage and neuroimmune reactions that increase risk for developing an alcohol use disorder (AUD). Adolescent female drinking patterns have surpassed males, yet little is known about damaging effects of alcohol in females. Known sex differences in neuroimmune reactivity, specifically microglial reactivity, suggest that the female brain will differ from males. Therefore, we examined indicators of neuroimmune activation and neurodegeneration following 2 days of heavy, bingelike exposure in adolescent male and female rats. Translocator protein 18kD (TSPO) expression assessed by [³H]PK-11195 autoradiography revealed that adolescent female rats showed a brief and immediate response in the thalamus, while male rats showed a delayed and sustained increase in the thalamus and hippocampus versus same-sex controls. Neurodegeneration assessed by Fluoro-Jade-B (FJB) dye showed that alcohol-induced cell death was modest for both sexes. Males showed cell death in the entorhinal cortex while females showed greater cell death in the perirhinal and piriform cortices. Additional neuroimmune measures of pro-inflammatory cytokine, IL-6, was decreased in the hippocampus and entorhinal cortex a week after alcohol exposure in females only. No changes in brain-derived neurotrophic factor (BDNF) were found in either sex or region. Overall, these experiments show adolescent females and males display unique neuroimmune responses and neurodegeneration profiles following heavy binge-like exposure. These data imply that females show a impaired neuroimmune response to alcohol that could contribute to sex differences in damage and deficits caused by alcohol.

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青春期大鼠大量饮酒后神经免疫反应的性别差异

酗酒的青少年普遍酗酒，这与脑损伤和神经免疫反应有关，增加了患酒精使用障碍（AUD）的风险。青少年女性的饮酒模式已经超过了男性，但人们对酒精对女性的破坏性影响知之甚少。已知的神经免疫反应性的性别差异，特别是小胶质反应性，表明女性大脑与男性不同。因此，我们检测了青春期雄性和雌性大鼠在重度暴饮暴露2天后的神经免疫激活和神经变性指标。通过[3H]PK-11195放射自显影技术评估的转运蛋白18kD （TSPO）表达显示，与同性对照相比，青春期雌性大鼠在丘脑中表现出短暂而立即的反应，而雄性大鼠在丘脑和海马中表现出延迟和持续的增加。氟玉- b （FJB）染料评估的神经退行性变显示，酒精诱导的细胞死亡对两性都是适度的。雄鼠的内嗅皮质细胞死亡，而雌鼠的内嗅周围和梨状皮质细胞死亡更严重。仅在女性中，酒精暴露一周后，海马体和内嗅皮层中促炎细胞因子IL-6的额外神经免疫测量值降低。脑源性神经营养因子（BDNF）在性别和地区均未见变化。总的来说，这些实验表明青春期女性和男性在大量暴饮暴食后表现出独特的神经免疫反应和神经变性特征。这些数据表明，女性对酒精的神经免疫反应受损，这可能导致酒精造成的损伤和缺陷的性别差异。

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来源期刊

Journal of neuroimmunology 医学-免疫学

CiteScore

6.10

自引率

3.00%

发文量

154

审稿时长

37 days

期刊介绍： The Journal of Neuroimmunology affords a forum for the publication of works applying immunologic methodology to the furtherance of the neurological sciences. Studies on all branches of the neurosciences, particularly fundamental and applied neurobiology, neurology, neuropathology, neurochemistry, neurovirology, neuroendocrinology, neuromuscular research, neuropharmacology and psychology, which involve either immunologic methodology (e.g. immunocytochemistry) or fundamental immunology (e.g. antibody and lymphocyte assays), are considered for publication.