TNF-α from hippocampal microglia induces working memory deficits by acute stress in mice

Masahiro Ohgidani, Takahiro A. Kato, Noriaki Sagata, Kohei Hayakawa, Norihiro Shimokawa, Mina Sato-Kasai, Shigenobu Kanba

Research output: Contribution to journalArticlepeer-review

58 Citations (Scopus)


The role of microglia in stress responses has recently been highlighted, yet the underlying mechanisms of action remain unresolved. The present study examined disruption in working memory due to acute stress using the water-immersion resistant stress (WIRS) test in mice. Mice were subjected to acute WIRS, and biochemical, immunohistochemical, and behavioral assessments were conducted. Spontaneous alternations (working memory) significantly decreased after exposure to acute WIRS for 2 h. We employed a 3D morphological analysis and site- and microglia-specific gene analysis techniques to detect microglial activity. Morphological changes in hippocampal microglia were not observed after acute stress, even when assessing ramification ratios and cell somata volumes. Interestingly, hippocampal tumor necrosis factor (TNF)-α levels were significantly elevated after acute stress, and acute stress-induced TNF-α was produced by hippocampal-ramified microglia. Conversely, plasma concentrations of TNF-α were not elevated after acute stress. Etanercept (TNF-α inhibitor) recovered working memory deficits in accordance with hippocampal TNF-α reductions. Overall, results suggest that TNF-α from hippocampal microglia is a key contributor to early-stage stress-to-mental responses.

Original languageEnglish
Pages (from-to)17-24
Number of pages8
JournalBrain, Behavior, and Immunity
Publication statusPublished - Jul 1 2016

All Science Journal Classification (ASJC) codes

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience


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