Current Issue

Inhibition of activation of astrocytes in dorsal hippocampal CA1 relieves lipopolysaccharide-induced cognitive impairment

JING Si-Qi¹, ZHANG Ying², SHI Wei-Guo², TONG Kun³, KONG Guan-Xiang^2,*

¹School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou 221000, China；²Department of Anesthesiology, Shuyang Hospital of Traditional Chinese Medicine, Shuyang 223600, China；³Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, China

Abstract

This study aimed to investigate whether inhibiting the activation of astrocytes in the dorsal hippocampal CA1 (dCA1) region could ameliorate lipopolysaccharide (LPS)-induced cognitive impairment in mice. Mice were intraperitoneally injected with LPS to establish a cognitive impairment model, and received intraperitoneal injection of rapamycin or chemogenetic inhibition of astrocytes in the dCA1 region. Behavioral experiments were used to detect activity and cognitive ability of mice. Immunofluorescence staining was employed to detect the expression of glial fibrillary acidic protein (GFAP), neuronal immediate early gene protein c-Fos, and γ-aminobutyric acid (GABA) in the dCA1 region of mice. The results showed that, compared with the control group, the LPS group exhibited no significant change in locomotor activity but a marked decrease in fear memory. Meanwhile, GFAP expression in the dCA1 was up-regulated, while the number of neurons co-expressing c-Fos and GABA was significantly reduced. Rapamycin significantly alleviated LPS-induced fear memory impairment, down-regulated GFAP expression in the dCA1 region, and increased the number of c-Fos/GABA co-expressing neurons. Additionally, chemogenetic inhibition of astrocytes in the dCA1 remarkably mitigated fear memory impairment in LPS-treated mice. These findings suggest that LPS can induce astrocyte activation in the dCA1 region, reduce the activity of GABAergic neurons, and impair cognitive function in mice. Intraperitoneal injection of rapamycin or chemogenetics can improve neuroinflammation-induced cognitive impairment by inhibiting the activation of dCA1 astrocytes.

Key words: Rapamycin; hippocampal astrocytes; GABAergic neurons; cognitive impairment

Received: 　　Accepted:

Corresponding author: 孔贯祥　　E-mail:

DOI: 10.13294/j.aps.2025.0096

Citing This Article：

JING Si-Qi, ZHANG Ying, SHI Wei-Guo, TONG Kun, KONG Guan-Xiang. Inhibition of activation of astrocytes in dorsal hippocampal CA1 relieves lipopolysaccharide-induced cognitive impairment. Acta Physiol Sin 2025; 77 (6): 1148-1156 (in Chinese with English abstract).