Variability in Behavioral Phenotypes after Forced Swimming-Induced Stress in Rats Is Associated with Expression of the Glucocorticoid Receptor, Nurr1, and IL-1β in the Hippocampus

Int J Mol Sci. 2021 Nov 24;22(23):12700. doi: 10.3390/ijms222312700.

Abstract

Individual differences in coping with stress may determine either a vulnerable or resilient phenotype. Therefore, it is important to better understand the biology underlying the behavioral phenotype. We assessed whether individual behavioral phenotype to acute stress is related with the hippocampal expression of glucocorticoid receptor (GR), Nurr1, interleukin-1 beta (IL-1β) or brain-derived neurotrophic factor (BDNF). Wistar male rats were exposed to forced swimming for 15 min and sacrificed at different times. Behavioral response was analyzed, and it was compared with the gene and protein expression of GR, Nurr1, IL-1β and BDNF in the hippocampus for each time point. Behavioral phenotyping showed a group with high immobility (vulnerable) while another had low immobility (resilient). No significant differences were found in the Nurr1, IL-1β and BDNF mRNA levels between resilient and vulnerable rats at different recovery times except for Nr3c1 (gene for GR). However, exposure to stress caused significantly higher levels of GR, Nurr1 and IL-1β proteins of vulnerable compared to resilient rats. This variability of behavioral phenotypes is associated with a differential molecular response to stress that involves GR, Nurr1, and IL-1β as mediators in coping with stress. This contributes to identifying biomarkers of susceptibility to stress.

Keywords: IL-1β; Nurr1; behavioral phenotype; glucocorticoid receptor; individual differences; resilient phenotype; stress resilience; vulnerable phenotype.

MeSH terms

  • Adaptation, Psychological
  • Animals
  • Behavior, Animal / physiology*
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Disease Models, Animal
  • Female
  • Hippocampus / metabolism*
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism*
  • Male
  • Nuclear Receptor Subfamily 4, Group A, Member 2 / genetics
  • Nuclear Receptor Subfamily 4, Group A, Member 2 / metabolism*
  • Phenotype
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Glucocorticoid / genetics
  • Receptors, Glucocorticoid / metabolism*
  • Stress, Psychological*
  • Swimming*

Substances

  • Bdnf protein, rat
  • Brain-Derived Neurotrophic Factor
  • IL1B protein, rat
  • Interleukin-1beta
  • Nr4a2 protein, rat
  • Nuclear Receptor Subfamily 4, Group A, Member 2
  • RNA, Messenger
  • Receptors, Glucocorticoid