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Sex differences in gut microbiota modulation of aversive conditioning, open field activity, and basolateral amygdala dendritic spine density
Journal of Neuroscience Research ( IF 4.2 ) Pub Date : 2021-05-05 , DOI: 10.1002/jnr.24848
Caroline Grace Geary 1 , Victoria Christina Wilk 2 , Katherine Louise Barton 1 , Parvaneh Ottavia Jefferson 1 , Tea Binder 2 , Vasvi Bhutani 1 , Claire Luisa Baker 1 , Achal James Fernando-Peiris 2 , Alexa Lee Mousley 1 , Stefano Freitas Andrade Rozental 1 , Hannah Mae Thompson 1 , Justin Charles Touchon 2 , David Justin Esteban 2 , Hadley Creighton Bergstrom 1
Affiliation  

Gut microbiota influence numerous aspects of host biology, including brain structure and function. Growing evidence implicates gut microbiota in aversive conditioning and anxiety-related behaviors, but research has focused almost exclusively on males. To investigate whether effects of gut dysbiosis on aversive learning and memory differ by sex, adult female and male C57BL/6N mice were orally administered a moderate dose of nonabsorbable antimicrobial medications (ATMs: neomycin, bacitracin, and pimaricin) or a control over 10 days. Changes in gut microbiome composition were analyzed by 16S rRNA sequencing. Open field behavior, cued aversive learning, context recall, and cued recall were assessed. Following behavioral testing, the morphology of basolateral amygdala (BLA) principal neuron dendrites and spines was characterized. Results revealed that ATMs induced gut dysbiosis in both sexes, with stronger effects in females. ATMs also exerted sex-specific effects on behavior and neuroanatomy. Males were more susceptible than females to microbial modulation of locomotor activity and anxiety-like behavior. Females were more susceptible than males to ATM-induced impairments in aversive learning and cued recall. Context recall remained intact, as did dendritic structure of BLA principal neurons. However, ATMs exerted a sex-specific effect on spine density. A second experiment was conducted to isolate the effects of gut perturbation to cued recall. Extinction was also examined. Results revealed no effect of ATMs on cued recall or extinction, suggesting that gut dysbiosis preferentially impacts aversive learning. These data shed new light on how gut microbiota interact with sex to influence aversive conditioning, open field behavior, and BLA dendritic spine architecture.

中文翻译:

肠道微生物群调节厌恶调节、开放场活动和基底外侧杏仁核树突棘密度的性别差异

肠道微生物群影响宿主生物学的许多方面,包括大脑结构和功能。越来越多的证据表明肠道微生物群与厌恶性调节和焦虑相关的行为有关,但研究几乎完全集中在男性身上。为了研究肠道菌群失调对厌恶性学习和记忆的影响是否因性别而异,成年雌性和雄性 C57BL/6N 小鼠口服中等剂量的不可吸收的抗菌药物(ATM:新霉素、杆菌肽和匹马霉素)或对照组超过 10 天. 通过 16S rRNA 测序分析肠道微生物组组成的变化。评估了开放领域行为、线索厌恶学习、上下文回忆和线索回忆。在行为测试之后,对基底外侧杏仁核 (BLA) 主要神经元树突和棘的形态进行了表征。结果表明,自动取款机会导致两性肠道菌群失调,对女性的影响更大。自动取款机还对行为和神经解剖学产生了性别特异性影响。男性比女性更容易受到微生物对运动活动和焦虑样行为的调节。女性比男性更容易受到 ATM 引起的厌恶学习和线索回忆障碍的影响。上下文回忆保持完整,BLA 主要神经元的树突结构也是如此。然而,自动取款机对脊柱密度产生了特定性别的影响。进行了第二个实验以分离肠道扰动对提示回忆的影响。还检查了灭绝。结果显示 ATM 对提示回忆或消退没有影响,这表明肠道菌群失调优先影响厌恶性学习。
更新日期:2021-07-08
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