Probiotic treatment reduces the autistic-like excitation/inhibition imbalance in juvenile hamsters induced by orally administered propionic acid and clindamycin
Probiotic treatment reduces the autistic-like excitation/inhibition imbalance in juvenile hamsters induced by orally administered propionic acid and clindamycin
复制标题
DOI：
10.1007/s11011-018-0212-8
复制
发表时间：
2018-08-01
影响因子：
3.6
通讯作者：
Abed, Kawther
中科院分区：
文献类型：
--
作者：
El-Ansary, Afaf;Ben Bacha, Abir;Abed, Kawther
越来越多的证据表明，肠道微生物群在中枢神经系统（CNS）中起着关键作用，由于环境因素导致的肠道微生物群组成的改变可能导致神经发育障碍。动物模型可能有助于确定可以使改变的肠道微生物群正常化的药物，从而改善异常的大脑信号通路。本研究的目的是研究益生菌如双歧杆菌和乳酸杆菌对克林霉素和丙酸（PPA）诱导的幼年仓鼠谷氨酸兴奋毒性的治疗效力。50只体重在60和70 g之间的年轻叙利亚金黄仓鼠参加了这项研究。将仓鼠随机分为5组，每组10只。对照组仓鼠仅口服磷酸盐缓冲盐水。PPA治疗组接受神经毒性剂量250 mg PPA/kg体重（BW）/天，持续3天。克林霉素给药组在实验开始当天接受30 mg克林霉素/kg BW单次口胃给药。两个治疗组接受相同剂量的PPA和克林霉素，然后接受0.2 g益生菌/kg BW，持续三周。在每组仓鼠的脑匀浆中研究与谷氨酸兴奋毒性相关的生化参数。此外，在所有组的粪便样品中监测致病菌的发展。本研究的微生物学结果显示，克林霉素和PPA处理仓鼠的粪便微生物群和梭菌属出现描述性变化。此外，益生菌在恢复正常肠道微生物群中的有效性也得到了证明。此外，克林霉素和PPA被发现，诱导Mg ~（2+）和γ-氨基丁酸（GABA）的显着消耗和Na ~+/Mg ~（2+）和谷氨酸/GABA的比值显着增加，但在K ~+，Na ~+和谷氨酸的绝对水平的无显着变化。本研究中PPA和克林霉素诱导的细菌过度生长有效地显示了神经元毒性的迹象。研究表明，益生菌可以安全地用于改善谷氨酸兴奋毒性，主要是通过增加耗尽的GABA和Mg 2+，减少兴奋性神经递质谷氨酸。
Increasing evidence suggests that the gut microbiota plays a key role in the central nervous system (CNS), and alterations of the gut microbiota composition due to environmental factors can contribute to neurodevelopmental disorders. Animal modeling may help to identify drugs that can normalize the altered gut microbiota and thereby ameliorate abnormal brain signaling pathways. The purpose of the present study was to investigate the therapeutic potency of probiotics such as Bifidobacteria and Lactobacilli on glutamate excitotoxicity as a neurotoxic effect induced by clindamycin and propionic acid (PPA) in juvenile hamsters. Fifty young golden Syrian hamsters weighing between 60 and 70 g were enrolled in the study. The hamsters were randomly divided into five groups, each with ten hamsters. The hamsters in the control group only received phosphate-buffered saline orally. The PPA-treated group received a neurotoxic dose of 250 mg PPA/kg body weight (BW)/day for three days. The clindamycin-treated group received 30 mg clindamycin/kg BW as a single orogastric dose on the day the experiment started. The two therapeutic groups received the same doses of PPA and clindamycin followed by 0.2 g probiotic/kg BW for three weeks. Biochemical parameters related to glutamate excitotoxicity were investigated in brain homogenates from each group of hamsters. Additionally, the development of pathogenic bacteria was monitored in stool samples from all groups. The microbiology results of the present study revealed descriptive changes in the fecal microbiota and the appearance of Clostridium species in the hamsters treated with clindamycin and PPA. Additionally, the effectiveness of the probiotic in the restoration of the normal gut microbiota was demonstrated. Moreover, clindamycin and PPA were found to induce a significant depletion of Mg2+ and gamma-aminobutyric acid (GABA) and a remarkable increase in the Na+/Mg2+ and glutamate/GABA ratios but non-significant changes in the absolute levels of K+, Na+ and glutamate. The bacteria overgrowth induced by PPA and clindamycin in the present study effectively showed signs of neuronal toxicity. The study indicates that probiotics can be used safely to ameliorate glutamate excitotoxicity mostly through increasing depleted GABA and Mg2+ and decreasing the excitatory neurotransmitter, glutamate.