We aimed to evaluate the effects of EPO in the lipopolysaccharide (LPS) induced rat model of autism in terms of social deficits, learning and memory impairments, as well as their neurochemical correlates. Sixteen female Sprague Dawley rats randomly distributed into two equel groups, then were caged with fertile males for mating. At the 10th day of pregnancy, 0.5 ml %0,9 NaCl saline was given to first group, 100 μg/kg LPS was given to second group to induce autism. On postnatal 21th day, forty-eight littermates were divided into four groups as; 8 male, 8 female controls, 16 male and 16 female LPS-exposed. Then, LPS groups were also divided in to two groups as saline (1 mg/kg/day) and EPO 600 U/kg/day groups, and animals were treated 45 days. At 50th day, after behavioral evaluations, brain levels of TNF-α, nerve growth factor (NGF) were measured. Histologically, hippocampal neuronal density and GFAP expression were assessed. Three-chamber sociability and social novelty test, passive avoidance learning test were revealed significant differences among the EPO and control groups. Histologically, hippocampal CA1 & CA3 regions displayed significant alterations regarding gliosis (GFAP-positive cells) and regarding frontal cortical thickness in EPO groups compare to controls. Biochemical measurements of the brain levels of TNF-α and NGF levels showed significant differences between controls and EPO groups. According to our findings EPO treatment has beneficial effects on ASD-like symptoms, learning and memory processes, neuronal loss and neuroinflammation in the LPS induced rat model of autism, with some gender differences through inflammatory and neurotrophic pathways.

中文翻译：

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促红细胞生成素对脂多糖诱导的自闭症大鼠模型中的社交缺陷、学习/记忆障碍、神经元丢失和神经炎症显示出性别依赖性的积极影响

我们旨在评估 EPO 在脂多糖 (LPS) 诱导的自闭症大鼠模型中在社交缺陷、学习和记忆障碍以及它们的神经化学相关性方面的影响。16只雌性Sprague Dawley大鼠随机分为两组，然后与可育雄性大鼠一起笼养交配。妊娠第10天，第一组给予0.5 ml %0,9 NaCl盐水，第二组给予100 μg/kg LPS诱导自闭症。出生后第21天，48只同窝仔被分为四组：8 名男性、8 名女性对照、16 名男性和 16 名女性暴露于 LPS。然后，LPS 组也分为生理盐水组（1 mg/kg/天）和 EPO 600 U/kg/天组，动物治疗 45 天。在第 50 天，行为评估后，测量脑中 TNF-α、神经生长因子 (NGF) 的水平。在组织学上，评估了海马神经元密度和 GFAP 表达。三室社交和社会新奇测试、被动回避学习测试显示EPO组和对照组之间存在显着差异。在组织学上，与对照组相比，EPO 组的海马 CA1 和 CA3 区域在神经胶质增生（GFAP 阳性细胞）和额叶皮质厚度方面显示出显着改变。TNF-α 和 NGF 水平的脑水平的生化测量显示对照组和 EPO 组之间存在显着差异。根据我们的研究结果，EPO 治疗对 LPS 诱导的自闭症大鼠模型中的 ASD 样症状、学习和记忆过程、神经元丢失和神经炎症具有有益影响，通过炎症和神经营养途径存在一些性别差异。评估海马神经元密度和GFAP表达。三室社交和社会新奇测试、被动回避学习测试显示EPO组和对照组之间存在显着差异。在组织学上，与对照组相比，EPO 组的海马 CA1 和 CA3 区域在神经胶质增生（GFAP 阳性细胞）和额叶皮质厚度方面显示出显着改变。TNF-α 和 NGF 水平的脑水平的生化测量显示对照组和 EPO 组之间存在显着差异。根据我们的研究结果，EPO 治疗对 LPS 诱导的自闭症大鼠模型中的 ASD 样症状、学习和记忆过程、神经元丢失和神经炎症具有有益影响，通过炎症和神经营养途径存在一些性别差异。评估海马神经元密度和GFAP表达。三室社交和社会新奇测试、被动回避学习测试显示EPO组和对照组之间存在显着差异。在组织学上，与对照组相比，EPO 组的海马 CA1 和 CA3 区域在神经胶质增生（GFAP 阳性细胞）和额叶皮质厚度方面显示出显着改变。TNF-α 和 NGF 水平的脑水平的生化测量显示对照组和 EPO 组之间存在显着差异。根据我们的研究结果，EPO 治疗对 LPS 诱导的自闭症大鼠模型中的 ASD 样症状、学习和记忆过程、神经元丢失和神经炎症具有有益影响，通过炎症和神经营养途径存在一些性别差异。