Short chain fatty acids, produced as gut microbiome metabolites but also present in the diet, exert broad effects in host physiology. Propionic acid (PPA), along with butyrate and acetate, plays a growing role in health, but also in neurological conditions. Increased PPA exposure in humans, animal models and cell lines elicit diverse behavioural and biochemical changes consistent with organic acidurias, mitochondrial disorders and autism spectrum disorders (ASD). ASD is considered a disorder of synaptic dysfunction and cell signalling, but also neuroinflammatory and neurometabolic components. We examined behaviour (Morris water and radial arm mazes) and the ultrastructure of the hippocampus and medial prefrontal cortex (electron microscopy) following a single intraperitoneal (i.p.) injection of PPA (175 mg/kg) in male adolescent rats. PPA treatment showed altered social and locomotor behaviour without changes in learning and memory. Both transient and enduring ultrastructural alterations in synapses, astro‐ and microglia were detected in the CA1 hippocampal area. Electron microscopic analysis showed the PPA treatment significantly decreased the total number of synaptic vesicles, presynaptic mitochondria and synapses with a symmetric active zone. Thus, brief systemic administration of this dietary and enteric short chain fatty acid produced behavioural and dynamic brain ultrastructural changes, providing further validation of the PPA model of ASD.

中文翻译：

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青春期雄性大鼠全身给药丙酸后的行为和脑超微结构变化。自闭症啮齿动物模型的进一步发展

短链脂肪酸作为肠道微生物组代谢物产生，但也存在于饮食中，对宿主生理学产生广泛影响。丙酸 (PPA) 以及丁酸盐和乙酸盐在健康和神经系统疾病中的作用越来越大。在人类、动物模型和细胞系中增加 PPA 暴露会引起与有机酸尿症、线粒体疾病和自闭症谱系障碍 (ASD) 一致的多种行为和生化变化。ASD 被认为是一种突触功能障碍和细胞信号传导的疾病，但也是神经炎症和神经代谢成分的疾病。我们检查了雄性青春期大鼠单次腹膜内 (ip) 注射 PPA (175 mg/kg) 后的行为（莫里斯水迷宫和桡臂迷宫）以及海马和内侧前额叶皮层的超微结构（电子显微镜）。PPA 治疗显示出社会和运动行为的改变，而学习和记忆没有改变。在 CA1 海马区检测到突触、星形胶质细胞和小胶质细胞的瞬时和持久超微结构改变。电子显微镜分析表明，PPA 处理显着减少了突触小泡、突触前线粒体和具有对称活动区的突触的总数。因此，这种饮食和肠道短链脂肪酸的短暂全身给药产生了行为和动态大脑超微结构的变化，进一步验证了 ASD 的 PPA 模型。电子显微镜分析表明，PPA 处理显着减少了突触小泡、突触前线粒体和具有对称活动区的突触的总数。因此，这种饮食和肠道短链脂肪酸的短暂全身给药产生了行为和动态大脑超微结构的变化，进一步验证了 ASD 的 PPA 模型。电子显微镜分析表明，PPA 处理显着减少了突触小泡、突触前线粒体和具有对称活动区的突触的总数。因此，这种饮食和肠道短链脂肪酸的短暂全身给药产生了行为和动态大脑超微结构的变化，进一步验证了 ASD 的 PPA 模型。