DataSheet1_LPS activates neuroinflammatory pathways to induce depression in Parkinson’s disease-like condition.ZIP

Aim: This study aimed to observe the effects of lipopolysaccharide (LPS) intraperitoneal (i.p.) injection on rats and investigate how neuroinflammation contributes to the pathogenesis of depression in Parkinson’s disease (dPD).
Methods: Rats were administered LPS (0.5 mg/kg, i.p.) for either 1, 2, or 4 consecutive days to establish a rat model of dPD. The sucrose preference test (SPT), the open field test (OFT), and the rotarod test evaluated depression-like and motor behaviors. Magnetic resonance imaging was used to detect alterations in the intrinsic activity and the integrity of white matter fibers in the brain. The expression of c-Fos, ionized calcium-binding adapter molecule (Iba-1), and tyrosine hydroxylase (TH) was evaluated using immunohistochemistry. The concentration of interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and interleukin-10 (IL-10) was measured using Luminex technology.
Results: LPS i.p. injections decreased sucrose preference in the SPT, horizontal and center distance in the OFT, and standing time in the rotarod test. The intrinsic activities in the hippocampus (HIP) were significantly reduced in the LPS-4 d group. The integrity of white matter fibers was greatly destroyed within 4 days of LPS treatment. The expression of c-Fos and Iba-1 in the prefrontal cortex, HIP, and substantia nigra increased dramatically, and the number of TH+ neurons in the substantia nigra decreased considerably after LPS injection. The levels of IL-6, TNF-α, and IL-10 were higher in the LPS-4 d group than those in the control group.
Conclusion: Injection of LPS (0.5 mg/kg, i.p.) for 4 consecutive days can activate microglia, cause the release of inflammatory cytokines, reduce intrinsic activities in the HIP, destroy the integrity of white matter fibers, induce anhedonia and behavioral despair, and finally lead to dPD. This study proved that LPS injection (0.5 mg/kg, i.p.) for 4 consecutive days could be used to successfully create a rat model of dPD.

研究目的：本研究旨在观察脂多糖（lipopolysaccharide, LPS）腹腔（intraperitoneal, i.p.）注射对大鼠的影响，并探讨神经炎症在帕金森病伴发抑郁（depression in Parkinson’s disease, dPD）发病机制中的作用。
实验方法：通过连续1、2或4天向大鼠腹腔注射脂多糖（0.5 mg/kg），以构建帕金森病伴发抑郁大鼠模型。采用蔗糖偏好实验（sucrose preference test, SPT）、旷场实验（open field test, OFT）以及转棒疲劳实验（rotarod test）评估大鼠的抑郁样行为与运动行为。利用磁共振成像检测大鼠脑内固有活动及白质纤维完整性的变化。通过免疫组织化学法检测c-Fos、离子钙结合衔接分子1（ionized calcium-binding adapter molecule 1, Iba-1）以及酪氨酸羟化酶（tyrosine hydroxylase, TH）的表达水平。采用Luminex液相芯片技术检测白细胞介素-6（interleukin-6, IL-6）、肿瘤坏死因子-α（tumor necrosis factor-α, TNF-α）以及白细胞介素-10（interleukin-10, IL-10）的浓度。
实验结果：腹腔注射脂多糖可降低蔗糖偏好实验中的蔗糖偏好率、旷场实验中的水平移动距离与中央区域活动距离，以及转棒疲劳实验中的停留时长。在脂多糖给药4天组（LPS-4 d组）中，大鼠海马（hippocampus, HIP）的固有活动显著降低。脂多糖给药4天内可显著破坏脑内白质纤维的完整性。脂多糖注射后，大鼠前额叶皮层、海马及黑质内的c-Fos与离子钙结合衔接分子1的表达水平显著升高，黑质内酪氨酸羟化酶阳性神经元的数量明显减少。与对照组相比，脂多糖给药4天组大鼠体内白细胞介素-6、肿瘤坏死因子-α及白细胞介素-10的浓度均显著升高。
研究结论：连续4天腹腔注射0.5 mg/kg脂多糖可激活小胶质细胞，促进炎性细胞因子释放，降低海马固有活动，破坏白质纤维完整性，诱导快感缺失与行为绝望，最终引发帕金森病伴发抑郁。本研究证实，连续4天腹腔注射0.5 mg/kg脂多糖可成功构建帕金森病伴发抑郁大鼠模型。