Delayed behavioral and genomic responses to acute combined stress in zebrafish, potentially relevant to PTSD and other stress-related disorders: Focus on neuroglia, neuroinflammation, apoptosis and epigenetic modulation

Long En Yang, Jingtao Wang, Dongmei Wang, Guojun Hu, Zi Yuan Liu, Dongni Yan, Nazar Serikuly, Erik T. Alpyshov, Konstantin A. Demin, Tatyana Strekalova, Murilo S. de Abreu, Cai Song, Allan V. Kalueff

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Stress is a common trigger of stress-related illnesses, such as anxiety, phobias, depression and post-traumatic stress disorder (PTSD). Various animal models successfully reproduce core behaviors of these clinical conditions. Here, we develop a novel zebrafish model of stress (potentially relevant to human stress-related disorders), based on delayed persistent behavioral, endocrine and genomic responses to an acute severe ‘combined’ stressor. Specifically, one week after adult zebrafish were exposed to a complex combined 90-min stress, we assessed their behaviors in the novel tank and the light-dark box tests, as well as whole-body cortisol and brain gene expression, focusing on genomic biomarkers of microglia, astrocytes, neuroinflammation, apoptosis and epigenetic modulation. Overall, stressed fish displayed persistent anxiety-like behavior, elevated whole-body cortisol, as well as upregulated brain mRNA expression of genes encoding the glucocorticoid receptor, neurotrophin BDNF and its receptors (TrkB and P75), CD11b (a general microglial biomarker), COX-2 (an M1-microglial biomarker), CD206 (an M2-microglial biomarker), GFAP (a general astrocytal biomarker), C3 (an A1-astrocytal biomarker), S100α10 (an A2-astrocytal biomarker), as well as pro-inflammatory cytokines IL-6, IL-1β, IFN-γ and TNF-α. Stress exposure also persistently upregulated the brain expression of several key apoptotic (Bax, Caspase-3, Bcl-2) and epigenetic genes (DNMT3a, DNMT3b, HAT1, HDAC4) in these fish. Collectively, the present model not only successfully recapitulates lasting behavioral and endocrine symptoms of clinical stress-related disorders, but also implicates changes in neuroglia, neuroinflammation, apoptosis and epigenetic modulation in long-term effects of stress pathogenesis in vivo.

Original languageEnglish
Article number112644
Number of pages9
JournalBehavioural Brain Research
Volume389
Early online date25 Apr 2020
DOIs
Publication statusPublished - 1 Jul 2020
Externally publishedYes

Keywords

  • Acute stress
  • Apoptosis
  • Astrocytes
  • Epigenetics
  • Microglia
  • Zebrafish
  • PSYCHOLOGICAL STRESS
  • DEPRESSION
  • ACUTE RESTRAINT STRESS
  • CHRONIC MILD STRESS
  • VULNERABILITY
  • POSTTRAUMATIC-STRESS
  • PREFRONTAL CORTEX
  • ANIMAL-MODELS
  • HPA AXIS
  • TRAUMA

Fingerprint

Dive into the research topics of 'Delayed behavioral and genomic responses to acute combined stress in zebrafish, potentially relevant to PTSD and other stress-related disorders: Focus on neuroglia, neuroinflammation, apoptosis and epigenetic modulation'. Together they form a unique fingerprint.

Cite this