Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Instituto de Cardiologia - Fundação Universitária de Cardiologia, Porto Alegre, Brazil.
Behav Brain Res. 2020 Feb 3;379:112360. doi: 10.1016/j.bbr.2019.112360. Epub 2019 Nov 14.
Peripheral inflammation promotes immune-to-brain communication, mediated by cytokines that affect brain activity. Lipopolysaccharide (LPS) has been widely used to mimic systemic inflammation, and the adipokine leptin, released in this condition, modulates hypothalamic leptin receptors (ObR), contributing to sickness behavior. In this study, we used the intracerebroventricular (ICV) route for LPS administration in an attempt to evaluate an acute and direct of this pathogen-associated molecular pattern on leptin-mediated signaling in the hippocampus, where ObR has been implicated in modulating cognitive response. We used bilateral ICV injection of LPS (25 μg/ventricle) in 60-day-old male Wistar rats and the analysis were performed 48 h after surgery. Neuroinflammation was characterized in the LPS group by an increase in concentration of IL-1β, COX-2 and TLR4 in the hippocampus as well as glial fibrillary acidic protein (GFAP), indicating an astrocyte commitment. Cognitive damage was observed in the animals of the LPS group by an inability to increase the recognition index during the object recognition test. We observed an increase in the concentration of leptin receptors in the hippocampus, which was unaccompanied by changes in the proteins involved in leptin intracellular signaling (p-STAT3 and SOCS3). Moreover, we found a decrease in leptin concentration in the serum of the animals in the LPS group accompanied by an increase in TNF-α levels. Our results showed that neuroinflammation, even in an acute state, can lead to cognitive impairment and may be associated with leptin signaling disturbances in the hippocampus.
外周炎症促进免疫向脑的通讯，这是由影响大脑活动的细胞因子介导的。脂多糖（LPS）已被广泛用于模拟全身炎症，而在这种情况下释放的脂肪因子瘦素调节下丘脑瘦素受体（ObR），导致疾病行为。在这项研究中，我们使用脑室内（ICV）途径给予 LPS 注射，试图评估这种病原体相关分子模式对海马中瘦素介导信号的急性和直接影响，ObR 已被认为在调节认知反应中起作用。我们在 60 天大的雄性 Wistar 大鼠中使用双侧 ICV 注射 LPS（25μg/脑室），并在手术后 48 小时进行分析。LPS 组的神经炎症表现为海马中 IL-1β、COX-2 和 TLR4 浓度增加以及胶质纤维酸性蛋白（GFAP）增加，表明星形胶质细胞的承诺。LPS 组的动物在物体识别测试中无法增加识别指数，表现出认知损伤。我们观察到海马中瘦素受体浓度增加，但与瘦素细胞内信号转导（p-STAT3 和 SOCS3）相关的蛋白质没有变化。此外，我们发现 LPS 组动物血清中的瘦素浓度降低，同时 TNF-α 水平升高。我们的结果表明，神经炎症，即使在急性状态下，也会导致认知障碍，并且可能与海马中瘦素信号转导的紊乱有关。
