Sepsis-associated encephalopathy (SAE) is a potentially irreversible acute cognitive dysfunction with unclear mechanism. Striatal-enriched protein tyrosine phosphatase (STEP) is a brain-specific phosphatase which normally opposes synaptic strengthening by regulating key signaling molecules involved in synaptic plasticity and neuronal function. Thus, we hypothesized that abnormal STEP signaling pathway was involved in sepsis-induced cognitive impairment evoked by lipopolysaccharides (LPS) injection. The levels of STEP, phosphorylation of GluN2B (pGluN2B), the kinases extracellular signal-regulated kinase 1/2 (pERK), cAMP-response element binding protein (CREB), synaptophysin, brain derived neurotrophic factor (BDNF), and post-synaptic density protein 95 (PSD95) in the hippocampus, prefrontal cortex, and striatum were determined at the indicated time points. In the present study, we found that STEP levels were significantly increased in the hippocampus, prefrontal cortex, and striatum following LPS injection, which might resulted from the disruption of the ubiquitin–proteasome system. Notably, a STEP inhibitor TC-2153 treatment alleviated sepsis-induced memory impairment by increasing phosphorylation of GluN2B and ERK1/2, CREB/BDNF, and PSD95. In summary, our results support the key role of STEP in sepsis-induced memory impairment in a mouse model of SAE, whereas inhibition of STEP may provide a novel therapeutic approach for this disorder and possible other neurodegenerative diseases.

败血症相关性脑病（SAE）是一种潜在的不可逆的急性认知功能障碍，其机制尚不清楚。纹状体富集的蛋白酪氨酸磷酸酶（STEP）是一种大脑特异性的磷酸酶，通常通过调节参与突触可塑性和神经元功能的关键信号分子来反对突触增强。因此，我们假设脂多糖（LPS）注射诱发败血症诱导的认知功能障碍涉及异常的STEP信号通路。STEP的水平，GluN2B的磷酸化（pGluN2B），激酶细胞外信号调节激酶1/2（pERK），cAMP反应元件结合蛋白（CREB），突触素，脑源性神经营养因子（BDNF）和突触后海马，前额叶皮层中的高密度蛋白95（PSD95）在指定的时间点确定纹状体和纹状体。在本研究中，我们发现LPS注射后海马，前额叶皮层和纹状体中的STEP水平显着增加，这可能是由于泛素-蛋白酶体系统的破坏所致。值得注意的是，STEP抑制剂TC-2153治疗可通过增加GluN2B和ERK1 / 2，CREB ​​/ BDNF和PSD95的磷酸化来减轻败血症引起的记忆障碍。总而言之，我们的研究结果支持STEP在SAE小鼠模型中败血症诱导的记忆障碍中的关键作用，而对STEP的抑制则可能为这种疾病和可能的其他神经退行性疾病提供一种新颖的治疗方法。LPS注射后的纹状体和纹状体，可能是由于泛素-蛋白酶体系统的破坏所致。值得注意的是，STEP抑制剂TC-2153治疗可通过增加GluN2B和ERK1 / 2，CREB ​​/ BDNF和PSD95的磷酸化来减轻败血症引起的记忆障碍。总而言之，我们的研究结果支持STEP在SAE小鼠模型中败血症诱导的记忆障碍中的关键作用，而对STEP的抑制则可能为这种疾病和可能的其他神经退行性疾病提供一种新颖的治疗方法。LPS注射后的纹状体和纹状体，可能是由于泛素-蛋白酶体系统的破坏所致。值得注意的是，STEP抑制剂TC-2153治疗可通过增加GluN2B和ERK1 / 2，CREB ​​/ BDNF和PSD95的磷酸化来减轻败血症引起的记忆障碍。总而言之，我们的研究结果支持STEP在SAE小鼠模型中败血症诱导的记忆障碍中的关键作用，而对STEP的抑制则可能为这种疾病和可能的其他神经退行性疾病提供一种新颖的治疗方法。