Lotan Dafna, Cunningham Madeleine, Joel Daphna
School of Psychological Sciences and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
PLoS One. 2014 Jun 30;9(6):e101257. doi: 10.1371/journal.pone.0101257. eCollection 2014.
Post-streptococcal A (GAS) sequelae including movement and neuropsychiatric disorders have been associated with improvement in response to antibiotic therapy. Besides eradication of infection, the underlying basis of attenuation of neuropsychiatric symptoms following antibiotic treatment is not known. The aim of the present study was to test the efficacy of antibiotic treatment in a rat model of GAS-related neuropsychiatric disorders. In the model, rats were not infected but were exposed to GAS-antigen or to adjuvants only (Control rats) and treated continuously with the antibiotic ampicillin in their drinking water from the first day of GAS-antigen exposure. Two additional groups of rats (GAS and Control) did not receive ampicillin in their drinking water. Behavior of the four groups was assessed in the forced swim, marble burying and food manipulation assays. We assessed levels of D1 and D2 dopamine receptors and tyrosine hydroxylase in the prefrontal cortex and striatum, and IgG deposition in the prefrontal cortex, striatum and thalamus. Ampicillin treatment prevented emergence of the motor and some of the behavioral alterations induced by GAS-antigen exposure, reduced IgG deposition in the thalamus of GAS-exposed rats, and tended to attenuate the increase in the level of TH and D1 and D2 receptors in their striatum, without concomitantly reducing the level of sera anti-GAS antibodies. Our results reinforce the link between exposure to GAS antigen, dysfunction of central dopaminergic pathways and motor and behavioral alterations. Our data further show that some of these deleterious effects can be attenuated by antibiotic treatment, and supports the latter's possible efficacy as a prophylactic treatment in GAS-related neuropsychiatric disorders.
包括运动和神经精神障碍在内的A组链球菌（GAS）后遗症与抗生素治疗反应的改善有关。除了根除感染外，抗生素治疗后神经精神症状减轻的潜在基础尚不清楚。本研究的目的是在GAS相关神经精神障碍的大鼠模型中测试抗生素治疗的效果。在该模型中，大鼠未被感染，但仅暴露于GAS抗原或佐剂（对照大鼠），并从暴露于GAS抗原的第一天起在饮用水中持续给予抗生素氨苄青霉素。另外两组大鼠（GAS组和对照组）在饮用水中未接受氨苄青霉素。通过强迫游泳、埋大理石和食物操作试验评估四组大鼠的行为。我们评估了前额叶皮质和纹状体中D1和D2多巴胺受体以及酪氨酸羟化酶的水平，以及前额叶皮质、纹状体和丘脑中IgG的沉积。氨苄青霉素治疗可预防由GAS抗原暴露诱导的运动和一些行为改变的出现，减少暴露于GAS的大鼠丘脑中的IgG沉积，并倾向于减弱其纹状体中TH、D1和D2受体水平的升高，而不会同时降低血清抗GAS抗体的水平。我们的结果强化了GAS抗原暴露、中枢多巴胺能途径功能障碍与运动和行为改变之间的联系。我们的数据进一步表明，抗生素治疗可以减轻其中一些有害影响，并支持其作为GAS相关神经精神障碍预防性治疗的可能疗效。
