Repeated social defeat induces transient glial activation and brain hypometabolism: A positron emission tomography imaging study

Paula Kopschina Feltes, Erik Fj de Vries, Luis E Juarez-Orozco, Ewelina Kurtys, Rudi Ajo Dierckx, Cristina M Moriguchi-Jeckel, Janine Doorduin*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

8 Citations (Scopus)
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Abstract

Psychosocial stress is a risk factor for the development of depression. Recent evidence suggests that glial activation could contribute to the development of depressive-like behaviour. This study aimed to evaluate in vivo whether repeated social defeat (RSD) induces short- and long-term inflammatory and metabolic alterations in the brain through positron emission tomography (PET). Male Wistar rats ( n = 40) were exposed to RSD by dominant Long-Evans rats on five consecutive days. Behavioural and biochemical alterations were assessed at baseline, day 5/6 and day 24/25 after the RSD protocol. Glial activation (11C-PK11195 PET) and changes in brain metabolism (18F-FDG PET) were evaluated on day 6, 11 and 25 (short-term), and at 3 and 6 months (long-term). Defeated rats showed transient depressive- and anxiety-like behaviour, increased corticosterone and brain IL-1β levels, as well as glial activation and brain hypometabolism in the first month after RSD. During the third- and six-month follow-up, no between-group differences in any investigated parameter were found. Therefore, non-invasive PET imaging demonstrated that RSD induces transient glial activation and reduces brain glucose metabolism in rats. These imaging findings were associated with stress-induced behavioural changes and support the hypothesis that neuroinflammation could be a contributing factor in the development of depression.

Original languageEnglish
Pages (from-to)439-453
Number of pages15
JournalJournal of Cerebral Blood Flow and Metabolism
Volume39
Issue number3
Early online date22-Dec-2017
DOIs
Publication statusPublished - Mar-2019

Keywords

  • Brain metabolism
  • depression
  • neuroinflammation
  • positron emission tomography imaging
  • repeated social defeat
  • ANXIETY-LIKE BEHAVIOR
  • ELEVATED PLUS-MAZE
  • BENZODIAZEPINE-RECEPTOR
  • OBJECT RECOGNITION
  • MEMORY IMPAIRMENT
  • MAJOR DEPRESSION
  • ANIMAL-MODEL
  • RAT-BRAIN
  • STRESS
  • CORTEX

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