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Original Research | Open Access

Comparison of chronic restraint stress-and lipopolysaccharide-induced mouse models of depression: Behavior, c-Fos expression, and microglial and astrocytic activation

Lingyu Zhanga,b,1Caizhuo Caoc,1Changyi Luoa,bHuaqiang RuanbChuang XubYan Wangc( )Xiaoxia Jiangb( )Gengsheng Maoa,d( )
Clinical College of the Third Medical Center of Chinese PLA General Hospital, The Fifth School of Clinical Medical, Anhui Medical University, Hefei 230032, Anhui, China
Beijing Institute of Basic Medical Sciences, Beijing 100850, China
School of Basic Medical Science, Anhui Medical University, Hefei 230032, Anhui, China
Department of Neurosurgery, The Third Medical Centre Chinese People's Liberation Army General Hospital, Beijing 100039, China

1 Lingyu Zhang and Caizhuo Cao contributed equally.

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Abstract

Depression is a mental disease that involves a variety of complex physiological mechanisms. A wide range of methods have therefore been used to establish mouse models of depression, and there are currently many ways to develop such mouse models. The present study aimed to compare the effects of various model induction methods and assesses their different effects. To this end, C57BL/6J mice were divided into three experimental groups: the chronic restraint stress (CRS) group received 6 hours of daily confinement within restraint tubes over a 3-week period; the chronic lipopolysaccharide (C-LPS) administration group received daily intraperitoneal injections of 0.5 mg/kg LPS for 1 week; and the acute LPS (A-LPS) administration group received a singular intraperitoneal injection of 0.83 mg/kg LPS. A corresponding control group was established for each experimental condition. Following mouse model establishment, depression-like behaviors were assessed through the forced swimming and tail suspension tests; anxiety-related behaviors were evaluated using the open field test and elevated plus maze. Furthermore, the expression of the immediate early gene c-Fos, ionized calcium-binding adapter molecule 1 (IBA1), and glial fibrillary acidic protein (GFAP) was examined via immunofluorescence. Longer immobility durations during the forced swimming and tail suspension tests were observed across all model groups (p < 0.05), indicating depression-like behaviors. Furthermore, the CRS and C-LPS group, but not the A-LPS group, showed significant anxiety-like behaviors in the elevated plus maze (p < 0.05). All model groups also exhibited significant increases in both time and distance explored within the central area of the open field test (p < 0.05). The activation of GFAP- and IBA1-positive cells in the cerebral cortex and hippocampus was also markedly pronounced in all experimental groups, suggesting the association of neuroinflammatory responses with induced depressive states. The present findings contribute to our understanding of the pathophysiology of stress-induced and neuroinflammatory-associated depression, and will help researchers to choose suitable depression models for their investigations.

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Journal of Neurorestoratology
Article number: 100130
Cite this article:
Zhang L, Cao C, Luo C, et al. Comparison of chronic restraint stress-and lipopolysaccharide-induced mouse models of depression: Behavior, c-Fos expression, and microglial and astrocytic activation. Journal of Neurorestoratology, 2024, 12(3): 100130. https://doi.org/10.1016/j.jnrt.2024.100130

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Received: 26 December 2023
Revised: 25 March 2024
Accepted: 09 May 2024
Published: 08 June 2024
© 2024.

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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