Neuroinflammatory dynamics underlie memory impairments after repeated social defeat

Daniel B. McKim, Anzela Niraula, Andrew J. Tarr, Eric S. Wohleb, John F. Sheridan, Jonathan P. Godbout

Research output: Contribution to journalArticlepeer-review

Abstract

Repeated social defeat (RSD) is a murine stressor that recapitulates key physiological, immunological, and behavioral alterations observed in humans exposed to chronic psychosocial stress. Psychosocial stress promotes prolonged behavioral adaptations that are associated with neuroinflammatory signaling and impaired neuroplasticity. Here, we show that RSD promoted hippocampal neuroinflammatory activation that was characterized by proinflammatory gene expression and by microglia activation and monocyte trafficking that was particularly pronounced within the caudal extent of the hippocampus. Because the hippocampus is a key area involved in neuroplasticity, behavior, and cognition,wehypothesize that stress-induced neuroinflammation impairs hippocampal neurogenesis and promotes cognitive and affective behavioral deficits. We show here that RSD caused transient impairments in spatial memory recall that resolved within 28 d. In assessment of neurogenesis, the number of proliferating neural progenitor cells (NPCs) and the number of young, developing neurons were not affected initially after RSD. Nonetheless, the neuronal differentiation of NPCs that proliferated during RSD was significantly impaired when examined 10 and 28 d later. In addition, social avoidance, a measure of depressive-like behavior associated with caudal hippocampal circuitry, persisted 28 d after RSD. Treatment with minocycline during RSD prevented both microglia activation and monocyte recruitment. Inhibition of this neuroinflammatory activation in turn prevented impairments in spatial memory after RSD but did not prevent deficits in neurogenesis nor did it prevent the persistence of social avoidance behavior. These findings show that neuroinflammatory activation after psychosocial stress impairs spatial memory performance independent of deficits in neurogenesis and social avoidance.

Original languageEnglish (US)
Pages (from-to)2590-2604
Number of pages15
JournalJournal of Neuroscience
Volume36
Issue number9
DOIs
StatePublished - Mar 2 2016

Keywords

  • Macrophages
  • Microglia
  • Neurogenesis
  • Neuroinflammation
  • Social avoidance
  • Stress

ASJC Scopus subject areas

  • General Neuroscience

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