Zou Jiao, Gao Junwei, Shang Weilong, Fan Xiaotang
Department of Military Cognitive Psychology, School of Psychology, Third Military Medical University (Army Medical University), Chongqing 400038, China.
Key Laboratory of Microbial Engineering Under the Educational Committee in Chongqing, Department of Microbiology, College of Basic Medical Sciences, Third Military Medical University (Army Medical University), Chongqing 400038, China.
Brain Sci. 2025 Jan 28;15(2):128. doi: 10.3390/brainsci15020128.
Anxiety disorders are the most common mental illnesses. is a Gram-positive opportunistic pathogen most commonly associated with anxiety-like behaviors. Minocycline ameliorates Gram-negative bacterial LPS-induced anxiety-like behaviors by suppressing microglia activation. However, the effects of minocycline on anxiety-like behaviors caused by infections have received little attention. In this study, we aimed to investigate the molecular mechanism and effect of minocycline on anxiety-like behaviors caused by infection. BV2 and N9 microglial cells were treated in vitro. The effects of minocycline on lipoteichoic acid (LTA)-stimulated inflammatory responses, STAT3 activation, and GLS1 expression were assessed using Western blotting, and cytokine secretion was determined using an ELISA. A mouse model was used to evaluate the capacity of minocycline to ameliorate anxiety-like behaviors caused by infection. We found that ≥100 μmol/L of minocycline remarkably attenuated LTA-induced TLR2 signaling pathway activation and proinflammatory cytokine expression in microglial cells. Minocycline prevented LTA-stimulated STAT3 activation and GLS1 expression in vitro. LTA-induced TLR2, TNF-α, IL-6, and GLS1 expression was markedly reduced by the inhibition of STAT3 phosphorylation. Mice were pretreated with 50 mg/kg of minocycline, significantly attenuating microglial activation and neuroinflammation. Minocycline also effectively alleviated the anxiety-like behaviors induced by infection. Our findings indicate that minocycline alleviates infection-induced anxiety-like behaviors by suppressing microglia activation.
焦虑症是最常见的精神疾病。[某种细菌名称]是一种革兰氏阳性机会致病菌，最常与焦虑样行为相关。米诺环素通过抑制小胶质细胞激活来改善革兰氏阴性细菌脂多糖诱导的焦虑样行为。然而，米诺环素对[细菌名称]感染引起的焦虑样行为的影响很少受到关注。在本研究中，我们旨在探讨米诺环素对[细菌名称]感染引起的焦虑样行为的分子机制和作用。体外处理BV2和N9小胶质细胞。使用蛋白质印迹法评估米诺环素对脂磷壁酸（LTA）刺激的炎症反应、STAT3激活和GLS1表达的影响，并使用酶联免疫吸附测定法测定细胞因子分泌。使用小鼠模型评估米诺环素改善[细菌名称]感染引起的焦虑样行为的能力。我们发现，≥100 μmol/L的米诺环素显著减弱了LTA诱导的小胶质细胞中TLR2信号通路激活和促炎细胞因子表达。米诺环素在体外阻止了LTA刺激的STAT3激活和GLS1表达。通过抑制STAT3磷酸化，LTA诱导的TLR2、TNF-α、IL-6和GLS1表达明显降低。用50 mg/kg的米诺环素预处理小鼠，显著减弱了小胶质细胞激活和神经炎症。米诺环素还有效减轻了[细菌名称]感染诱导的焦虑样行为。我们的研究结果表明，米诺环素通过抑制小胶质细胞激活来减轻[细菌名称]感染诱导的焦虑样行为。
