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), S100 alpha(10) (an A2-astrocytal biomarker), as well as pro-inflammatory cytokines IL-6, IL-1 beta, IFN-gamma and TNF-alpha. 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 language | English |
---|---|
Article number | 112644 |
Number of pages | 9 |
Journal | Behavioural Brain Research |
Volume | 389 |
DOIs | |
Publication status | Published - 1 Jul 2020 |
Keywords
- acute restraint stress
- acute stress
- animal-models
- apoptosis
- astrocytes
- chronic mild stress
- depression
- epigenetics
- hpa axis
- microglia
- posttraumatic-stress
- prefrontal cortex
- psychological stress
- trauma
- vulnerability
- zebrafish
- PSYCHOLOGICAL STRESS
- CHRONIC MILD STRESS
- VULNERABILITY
- POSTTRAUMATIC-STRESS
- ANIMAL-MODELS
- DEPRESSION
- Acute stress
- ACUTE RESTRAINT STRESS
- Astrocytes
- Zebrafish
- PREFRONTAL CORTEX
- Microglia
- Epigenetics
- HPA AXIS
- Apoptosis
- TRAUMA