PUBLICATION
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
- Authors
- 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.
- ID
- ZDB-PUB-200429-15
- 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*
- PubMed
- 32344037 Full text @ Behav. Brain Res.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping