OBJECTIVE Toll-like receptor-2 (TLR2), a member of TLR family, plays an important role in the induction and regulation of immune/inflammation. TLR2 gene knockout (TLR2KO) mice have been widely used for animal models of neurological diseases. Since there is close relationship between immune system and neurobehavioral functions, it is important to clarify the exact role of TLR2 defect itself in neurobehavioral functions. The present study aimed to investigate the effect of TLR2KO on neurobehavioral functions in mice and the mechanisms underlying the observed changes. METHODS Male TLR2KO and wild type (WT) mice aged 3, 7, and 12 months were used for neurobehavioral testing and detection of protein expression by Western blot. Brain magnetic resonance imaging (MRI), electrophysiological recording, and Evans blue (EB) assay were applied to evaluate regional cerebral blood flow (rCBF), synaptic function, and blood-brain barrier (BBB) integrity in 12-month-old TLR2KO and age-matched WT mice. RESULTS Compared to WT mice, TLR2KO mice showed decreased cognitive function and locomotor activity, as well as increased anxiety, which developed from middle age (before 7-month-old) to old age. In addition, significantly reduced regional cerebral blood flow (rCBF), inhibited long-term potentiation (LTP), and increased blood-brain barrier (BBB) permeability were observed in 12-month-old TLR2KO mice. Furthermore, compared with age-matched WT mice, significant reduction in protein levels of tight junction proteins (ZO-1, Occludin and Claudin5) and increased neurofilament protein (SMI32) were observed in 7 and 12-month-old TLR2KO mice, and that myelin basic protein (MBP) decreased in 12-month-old TLR2KO mice. CONCLUSION Our data demonstrated that TLR2 defect resulted in significantly observable neurobehavioral dysfunctions in mice starting from middle age, as well as multiple abnormalities in brain structure, function, and molecular metabolism.

中文翻译：

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Toll 样受体 2 基因敲除导致小鼠神经行为功能障碍和多种脑结构和功能异常

目的 Toll 样受体 2 (TLR2) 是 TLR 家族的一员，在免疫/炎症的诱导和调节中起重要作用。TLR2 基因敲除 (TLR2KO) 小鼠已广泛用于神经系统疾病的动物模型。由于免疫系统与神经行为功能之间存在密切关系，因此阐明 TLR2 缺陷本身在神经行为功能中的确切作用非常重要。本研究旨在研究 TLR2KO 对小鼠神经行为功能的影响以及观察到的变化的潜在机制。方法 3、7 和 12 个月的雄性 TLR2KO 和野生型 (WT) 小鼠用于神经行为测试和蛋白质印迹检测。脑磁共振成像（MRI），电生理记录，和伊文思蓝 (EB) 测定用于评估 12 个月大的 TLR2KO 和年龄匹配的 WT 小鼠的局部脑血流量 (rCBF)、突触功能和血脑屏障 (BBB) 完整性。结果 与 WT 小鼠相比，TLR2KO 小鼠表现出认知功能和运动活动下降，以及焦虑增加，从中年（7 个月前）发展到老年。此外，在 12 个月大的 TLR2KO 小鼠中观察到局部脑血流量 (rCBF) 显着降低、长时程增强 (LTP) 抑制和血脑屏障 (BBB) 通透性增加。此外，与年龄匹配的 WT 小鼠相比，在 7 和 12 个月大的 TLR2KO 小鼠中观察到紧密连接蛋白（ZO-1、Occludin 和 Claudin5）的蛋白质水平显着降低，神经丝蛋白（SMI32）增加，并且髓鞘碱性蛋白 (MBP) 在 12 个月大的 TLR2KO 小鼠中下降。结论 我们的数据表明，TLR2 缺陷导致小鼠从中年开始出现明显的神经行为功能障碍，以及大脑结构、功能和分子代谢的多种异常。