Microglial production of TNF-alpha is a key element of sustained fear memory

Zhiqian Yu, Hotaka Fukushima, Chiaki Ono, Mai Sakai, Yoshiyuki Kasahara, Yoshie Kikuchi, Nicole Gunawansa, Yuta Takahashi, Hiroo Matsuoka, Satoshi Kida, Hiroaki Tomita

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

The proinflammatory cytokine productions in the brain are altered in a process of fear memory formation, indicating a possibility that altered microglial function may contribute to fear memory formation. We aimed to investigate whether and how microglial function contributes to fear memory formation. Expression levels of M1- and M2-type microglial marker molecules in microglia isolated from each conditioned mice group were assessed by real-time PCR and immunohistochemistry. Levels of tumor necrosis factor (TNF)-α, but not of other proinflammatory cytokines produced by M1-type microglia, increased in microglia from mice representing retention of fear memory, and returned to basal levels in microglia from mice representing extinction of fear memory. Administration of inhibitors of TNF-α production facilitated extinction of fear memory. On the other hand, expression levels of M2-type microglia-specific cell adhesion molecules, CD206 and CD209, were decreased in microglia from mice representing retention of fear memory, and returned to basal levels in microglia from mice representing extinction of fear memory. Our findings indicate that microglial TNF-α is a key element of sustained fear memory and suggest that TNF-α inhibitors can be candidate molecules for mitigating posttraumatic reactions caused by persistent fear memory.

Original languageEnglish
Pages (from-to)313-321
Number of pages9
JournalBrain, Behavior, and Immunity
Volume59
DOIs
Publication statusPublished - 2017 Jan 1

Keywords

  • Extinction
  • Fear memory
  • Retention
  • TNF-alpha

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

Fingerprint Dive into the research topics of 'Microglial production of TNF-alpha is a key element of sustained fear memory'. Together they form a unique fingerprint.

Cite this