ZFIN ID: ZDB-PUB-200429-15
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
Yang, L., Wang, J., Wang, D., Hu, G., Liu, Z., Yan, D., Serikuly, N., Alpyshov, E., Demin, K.A., Strekalova, T., de Abreu, M.S., Song, C., Kalueff, A.
Date: 2020
Source: Behavioural brain research   389: 112644 (Journal)
Registered Authors: Kalueff, Allan V.
Keywords: Acute stress, apoptosis, astrocytes, epigenetics, microglia, zebrafish
MeSH Terms:
  • Animals
  • Apoptosis
  • Behavior, Animal*
  • Brain/metabolism*
  • Disease Models, Animal*
  • Encephalitis/metabolism
  • Epigenesis, Genetic
  • Female
  • Gene Expression*
  • Hydrocortisone/metabolism
  • Male
  • Neuroglia/metabolism
  • Stress Disorders, Post-Traumatic/metabolism*
  • Stress, Psychological/metabolism*
  • Zebrafish
PubMed: 32344037 Full text @ Behav. Brain Res.
Stress is a common trigger of stress-related disorders, 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. 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 the genes encoding the glucocorticoid receptor, neurotrophin BDNF and its receptors TrkB, 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 apoptotic (Bax, Caspase-3, Bcl-2) and epigenetic genes (DNMT3a, DNMT3b, HAT1, HDAC4) in these fish. Collectively, our findings suggest that the present model successfully recapitulates lasting behavioral and endocrine symptoms of clinical stress-related disorders, also implicating long-term changes in neuroglia, neuroinflammation, apoptosis and epigenetic modulation in their pathogenesis.