Campos Alline C, Rocha Natalia P, Nicoli Jacques R, Vieira Leda Q, Teixeira Mauro M, Teixeira Antonio L
Infectious Disease and Tropical Medicine Graduate Program, School of Medicine, UFMG, Belo Horizonte, MG, Brazil; Department of Pharmacology, School of Medicine of Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil.
Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Behav Brain Res. 2016 Oct 1;312:186-94. doi: 10.1016/j.bbr.2016.06.027. Epub 2016 Jun 15.
Changes in the microbiota composition of gastrointestinal tract are emerging as potential players in the physiopathology of neuropsychiatric disorders. In the present work we evaluated the relationship between the absence of gut microbiota and neuroinflammatory mechanisms in a murine model of LPS-induced behavioral alterations. Germ-free (GF) or conventional male mice received a single i.p. injection of lipopolysaccharide (LPS i.p.; 0.83mg/Kg) or PBS, and after 24h they were tested for depressive-like behaviors (forced swimming test, tail suspension test - TST, or sucrose preference test - SPT). After behavioral evaluation, animals were analyzed for possible changes in neuroplasticity by means of BDNF, NGF and cytokines levels in prefrontal cortex and hippocampus, and the expression of Iba-1 (microglial activation marker) in the hippocampus, and the cellular activity marker, ΔFosB, in the dorsal raphe nucleus. In conventional mice, LPS induced depressive-like behaviors. LPS-induced changes were followed by up-regulation of the expression of TNF and Iba-1 in the hippocampus. The same effects were not observed in GF mice. Behavioral effects of LPS were not observed in GF mice submitted to TST. GF mice present a lower response to the anhedonia-like effect induced by LPS when compared to conventional animals (SPT). There was up-regulation of ΔFosB in the dorsal raphe nucleus in the absence of gut microbiota, events not influenced by LPS treatment. Our results suggest that gut-microbiota interactions influence depressive-like behaviors, raphe nucleus activation and activation of pro-inflammatory mechanisms within the hippocampus.
胃肠道微生物群组成的变化正逐渐成为神经精神疾病生理病理学中的潜在因素。在本研究中，我们评估了无菌肠道微生物群与脂多糖（LPS）诱导的行为改变小鼠模型中神经炎症机制之间的关系。无菌（GF）或常规雄性小鼠腹腔注射一次脂多糖（腹腔注射LPS；0.83mg/Kg）或磷酸盐缓冲液（PBS），24小时后进行抑郁样行为测试（强迫游泳试验、悬尾试验-TST或蔗糖偏好试验-SPT）。行为评估后，通过检测前额叶皮质和海马中脑源性神经营养因子（BDNF）、神经生长因子（NGF）和细胞因子水平，以及海马中Iba-1（小胶质细胞激活标志物）的表达和背侧中缝核中的细胞活性标志物ΔFosB，分析动物神经可塑性的可能变化。在常规小鼠中，LPS诱导了抑郁样行为。LPS诱导的变化随后伴随着海马中肿瘤坏死因子（TNF）和Iba-1表达的上调。在GF小鼠中未观察到相同的效应。在接受TST的GF小鼠中未观察到LPS的行为效应。与常规动物相比，GF小鼠对LPS诱导的快感缺失样效应反应较低（SPT）。在没有肠道微生物群的情况下，背侧中缝核中的ΔFosB上调，这些事件不受LPS治疗的影响。我们的结果表明，肠道微生物群相互作用会影响抑郁样行为、中缝核激活以及海马内促炎机制的激活。
