Zhang Da-Qi, Dong Xiaoqian, Su Simin, Zhang Linlin, Zhang Jiayu, Yang Wenjing, Hu Wenting, Li Lushuang, Song Yanting, Xie Xi, Li Qifu, Wang Rong, Zhang Yingxia
Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Collaborative Innovation Center of One Health, Hainan University, Haikou, 570228, China.
Department of Neurology, the First Affiliated Hospital of Hainan Medical University, Haikou, 570102, China.
Probiotics Antimicrob Proteins. 2024 May 11. doi: 10.1007/s12602-024-10277-5.
Neuroinflammation is considered an important factor that leads to cognitive impairment. Microglia play a crucial role in neuroinflammation, which leads to cognitive impairment. This study aimed at determining whether temporin-GHaR peptide (GHaR) could improve cognitive function and at uncovering the underlying mechanisms. We found that GHaR treatment alleviated LPS-induced cognitive impairment and inhibited activation of microglia in LPS-induced mice. Furthermore, GHaR inhibited activation of endoplasmic reticulum stress (ERS) and the NF-κB signaling pathway in LPS-induced mice. In vitro, GHaR inhibited M1 polarization of BV2 cells and suppressed TNF-α and IL-6 secretion. Additionally, GHaR neuronal cell viability and apoptosis were induced by LPS-activated microglia-conditioned medium. Moreover, in LPS-induced BV2 cells, GHaR inhibited activation of ERS and the NF-κB signaling pathway. In summary, GHaR improved LPS-induced cognitive and attenuated inflammatory responses via microglial activation reversal. In conclusion, the neuroprotective effects of GHaR were mediated via the ERS signaling pathway.
神经炎症被认为是导致认知障碍的一个重要因素。小胶质细胞在神经炎症中起关键作用，而神经炎症会导致认知障碍。本研究旨在确定颞孔素-GHaR肽（GHaR）是否能改善认知功能，并揭示其潜在机制。我们发现，GHaR治疗可减轻脂多糖（LPS）诱导的小鼠认知障碍，并抑制LPS诱导的小鼠小胶质细胞活化。此外，GHaR抑制LPS诱导的小鼠内质网应激（ERS）和核因子κB（NF-κB）信号通路的激活。在体外，GHaR抑制BV2细胞的M1极化，并抑制肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的分泌。此外，GHaR可诱导LPS激活的小胶质细胞条件培养基诱导的神经元细胞活力和凋亡。此外，在LPS诱导的BV2细胞中，GHaR抑制ERS和NF-κB信号通路的激活。总之，GHaR通过逆转小胶质细胞活化改善LPS诱导的认知功能并减轻炎症反应。综上所述，GHaR的神经保护作用是通过ERS信号通路介导的。
