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Minocycline protects against lipopolysaccharide-induced cognitive impairment in mice

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Abstract

Rationale

The role of glial cells, especially microglia and astrocytes, in neuroinflammation and cognition has been studied intensively. Lipopolysaccharide (LPS), a commonly used inducer of neuroinflammation, can cause cognitive impairment. Minocycline is known to possess potent neuroprotective activity, but its effect on LPS-induced cognitive impairment is unknown.

Objectives

This study aims to investigate the effects of minocycline on LPS-induced cognitive impairment and glial cell activation in mice.

Methods

Behavioral tests were conducted for cognitive function, immunohistochemistry for microglial and astrocyte response, and quantitative PCR for mRNA expression of proinflammatory cytokines.

Results

Minocycline significantly reversed the decreased spontaneous alternation induced by intrahippocampal administration of LPS in the Y-maze task. In the Morris water maze place navigation test, minocycline decreased the escape latency and distance traveled compared to LPS-treated mice. In the probe test, minocycline-treated mice spent more time in the target quadrant and crossed the platform area more frequently than animals in the LPS-treated group. Minocycline produced a significant decrease in the number of Iba-1- and GFAP-positive hippocampal cells compared to the LPS-treated group. Minocycline-treated mice had significantly reduced hippocampal TNF-α and IL-1β mRNA levels compared with LPS-treated animals. Minocycline caused a significant increase in hippocampal BDNF expression compared to the LPS-treated group.

Conclusions

Minocycline can attenuate LPS-induced cognitive impairments in mice. This effect may be associated with its action to suppress the activation of microglia and astrocytes and to normalize BDNF expression. Since neuroinflammatory processes and cognitive impairments are implicated in neurodegenerative disorders, minocycline may be a promising candidate for treating such diseases.

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Acknowledgements

The authors gratefully acknowledge financial support from the National Natural Science Foundation of China (81102432, 81473330), the Fundamental Research Funds for the Central Universities of China (N130420004, N130120001), and Program for Liaoning Excellent Talents in University (LR2015022).

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Authors and Affiliations

  1. College of Life and Health Sciences, Northeastern University, 110004, Shenyang, China

    Yue Hou, Xia Liu, Guoxun Li, Congcong Jia & Bing Wang

  2. The 307th Hospital of Chinese People’s Liberation Army, 100071, Beijing, China

    Guanbo Xie

  3. Department of Pharmacology, Shenyang Pharmaceutical University, 110016, Shenyang, China

    Guanbo Xie, Xia Liu & Jinghua Xu

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  1. Yue Hou
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  2. Guanbo Xie
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  3. Xia Liu
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  4. Guoxun Li
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  5. Congcong Jia
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  6. Jinghua Xu
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  7. Bing Wang
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Correspondence to Jinghua Xu or Bing Wang.

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Hou, Y., Xie, G., Liu, X. et al. Minocycline protects against lipopolysaccharide-induced cognitive impairment in mice. Psychopharmacology 233, 905–916 (2016). https://doi.org/10.1007/s00213-015-4169-6

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  • DOI: https://doi.org/10.1007/s00213-015-4169-6

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