Early Life Stress and HPA Axis Programming in Rodent Models
Summary
Early life stress in rodents, typically induced by paradigms such as maternal separation, maternal deprivation or intermittent hypoxia, profoundly shapes the development of the hypothalamic–pituitary–adrenal (HPA) axis. During a defined stress-hyporesponsive period in the first two weeks of life, exposure to stressors elevates corticosterone secretions, alters glucocorticoid receptor expression in the hippocampus and amygdala, and triggers long-lasting changes in neuronal circuitry and neurotransmitter systems. These adaptations involve epigenetic programming of key genes regulating stress responses, with DNA methylation and histone modifications contributing to individual variability in resilience or vulnerability. Behavioural sequelae in adulthood include heightened anxiety- and depressive-like phenotypes, impaired social interactions and altered metabolic set-points. Such rodent models serve as invaluable tools for dissecting the molecular underpinnings of stress-related disorders in humans and for testing interventions aimed at reversing maladaptive programming.
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Early Life Stress and HPA Axis Programming in Rodent Models publication trend
The graph below shows the total number of articles in early life stress and hpa axis programming in rodent models across all publications each year (not limited to Nature Index journals).
Technical terms
Hypothalamic–Pituitary–Adrenal (HPA) axis: The neuroendocrine system that coordinates stress responses via sequential release of corticotropin-releasing factor, adrenocorticotropic hormone and glucocorticoids.
Maternal deprivation: Experimental removal of the dam from her litter for a defined period, used to model early life stress and its impact on offspring development.
Corticosterone: The principal glucocorticoid in rodents, released by the adrenal cortex in response to stress, influencing metabolism and brain function.
Epigenetic programming: Stable changes in gene expression potential through DNA methylation or chromatin modifications induced by early environmental factors.
References
- Neurobiological mechanisms involved in maternal deprivation-induced behaviours relevant to psychiatric disorders. Frontiers in Molecular Neuroscience (2023).
- Corticotropin-Releasing Factor Receptor 1 in the Anterior Cingulate Cortex Mediates Maternal Absence-Induced Attenuation of Transport Response in Mouse Pups. Frontiers in Cellular Neuroscience (2018).
- Sex Dimorphic Responses of the Hypothalamus–Pituitary–Thyroid Axis to Maternal Separation and Palatable Diet. Frontiers in Endocrinology (2019).
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