In this study, we investigated the potential role of C-X-C chemokine receptor type (CXCR) 5 in neurocognitive function in a mouse model of sepsis-associated encephalopathy (SAE). Adult male C57BL/6J mice received intracereboroventricular injections of small interfering RNAs (siRNAs) against CXCR5 or scrambled control siRNA. After 3 days, SAE was induced by cecal ligation and puncture (CLP, n=16 per group). Memory and learning ability were tested using the Morris water maze (MWM) on days 5-9 after CLP. Hippocampal expression of CXCR5, interleukin (IL)-1β and IL-6 were measured by western blot. Cell proliferation and the numbers of immature and mature neurons in the dentate gyrus were assessed by immunohistochemistry. CLP mice had deficits in memory and learning, as shown by increased latency in the MWM training sessions and decreased time spent in and crossing the target quadrant on day 9. CLP also increased the number of proliferating and immature neurons and decreased the number of mature neurons. This was accompanied by increased expression of CXCR5, IL-1β and IL-6 in the hippocampus. CXCR5 knockdown attenuated the memory and learning deficits induced by CLP and partially reversed the effects of CLP on numbers of proliferating, immature and mature neurons, and on expression of IL-1β and IL-6 in the hippocampus. These results suggest that CXCR5 knockdown can attenuate sepsis-induced deficits in hippocampal neurogenesis and cognitive function in mice with SAE.

在这项研究中，我们调查了脓毒症相关性脑病（SAE）小鼠模型中CXC趋化因子受体类型（CXCR）5在神经认知功能中的潜在作用。成年雄性C57BL / 6J小鼠接受脑室内注射针对CXCR5的小干扰RNA（siRNA）或加扰的对照siRNA。3天后，盲肠结扎和穿刺诱导出SAE（CLP，每组n = 16）。CLP后第5至9天使用Morris水迷宫（MWM）测试记忆力和学习能力。Western blot检测海马CXCR5，白介素（IL）-1β和IL-6的表达。通过免疫组织化学评估齿状回中的细胞增殖以及未成熟和成熟神经元的数量。CLP小鼠的记忆力和学习力不足，如MWM训练中的潜伏期增加以及第9天花费在目标象限和穿越目标象限的时间减少所显示的那样。CLP还增加了增殖和未成熟神经元的数量，并减少了成熟神经元的数量。这伴随着海马中CXCR5，IL-1β和IL-6表达的增加。CXCR5敲低减弱了CLP诱导的记忆和学习缺陷，部分逆转了CLP对增殖，未成熟和成熟神经元数量以及海马IL-1β和IL-6表达的影响。这些结果表明，CXCR5敲低可以减轻脓毒症诱发的SAE小鼠海马神经发生和认知功能的缺陷。CLP还增加了增殖和未成熟神经元的数量，并减少了成熟神经元的数量。这伴随着海马中CXCR5，IL-1β和IL-6表达的增加。CXCR5敲低减弱了CLP诱导的记忆和学习缺陷，部分逆转了CLP对增殖，未成熟和成熟神经元数量以及海马IL-1β和IL-6表达的影响。这些结果表明，CXCR5敲低可以减轻脓毒症诱发的SAE小鼠海马神经发生和认知功能的缺陷。CLP还增加了增殖和未成熟神经元的数量，并减少了成熟神经元的数量。这伴随着海马中CXCR5，IL-1β和IL-6表达的增加。CXCR5敲低减弱了CLP诱导的记忆和学习缺陷，部分逆转了CLP对增殖，未成熟和成熟神经元数量以及海马IL-1β和IL-6表达的影响。这些结果表明，CXCR5敲低可以减轻脓毒症诱发的SAE小鼠海马神经发生和认知功能的缺陷。对海马IL-1β和IL-6表达的影响 这些结果表明，CXCR5敲低可以减轻败血症诱导的SAE小鼠海马神经发生和认知功能的缺陷。对海马IL-1β和IL-6表达的影响 这些结果表明，CXCR5敲低可以减轻脓毒症诱发的SAE小鼠海马神经发生和认知功能的缺陷。