Abstract
The early life period represents a window of increased vulnerability to stress, during which exposure can lead to long-lasting effects on brain structure and function. This stress-induced developmental programming may contribute to the behavioural changes observed in mental illness. In recent decades, rodent studies have significantly advanced our understanding of how early life stress (ELS) affects brain development and behaviour. These studies reveal that ELS has long-term consequences on the brain such as impairment of adult hippocampal neurogenesis, altering learning and memory. Despite such advances, several key questions remain inadequately answered, including a comprehensive overview of brain regions and molecular pathways that are altered by ELS and how ELS-induced molecular changes ultimately lead to behavioural changes in adulthood. The zebrafish represents a novel ELS model, with the potential to contribute to answering some of these questions. The zebrafish offers some important advantages such as the ability to non-invasively modulate stress hormone levels in a whole animal and to visualise whole brain activity in freely behaving animals. This review discusses the current status of the zebrafish ELS field and its potential as a new ELS model.
Highlights
Stress disrupts homeostasis and drives an adaptive response, which protects an organism from damage (Chrousos, 2009)
Whilst the effects of stress in adulthood can be transient and reversible, stress during early life is associated with an alteration of the developmental trajectory of the brain, which can lead to Zebrafish Early Life Stress Model long lasting behavioural alterations (Danese and McEwen, 2012; Bick and Nelson, 2016; Teicher et al, 2016; Agorastos et al, 2019)
Significant progress has been made in recent decades in our understanding of how early life stress (ELS) affects brain development and behaviour largely thanks to rodent models
Summary
Stress disrupts homeostasis and drives an adaptive response, which protects an organism from damage (Chrousos, 2009). Zebrafish possess the Hypothalamo-Pituitary-Interrenal (HPI) axis, which is the homologue of the Hypothalamo-Pituitary-Adrenal (HPA) axis of the mammalian system Together, these features make zebrafish highly suitable as an ELS model, and in particular offer potential for detailed analysis of the underlying molecular mechanisms by which ELS affects the brain and behaviour and for drug discovery. Naturally occurring variation in maternal care cannot confound the early life experience of zebrafish larvae, allowing for a more uniform rearing environment among individuals Another consideration is that teleost fish have undergone a genome duplication event, and as such zebrafish possess two copies of some genes that are present in only a single copy in mammals (Howe et al, 2013). This review attempts to summarise and provide a contextual framework for the contributions made by the zebrafish work so far and highlights major issues for future work in this exciting and burgeoning field
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