Glucocorticoid effects on the brain: from adaptive developmental plasticity to allostatic overload

Abstract

Exposure to stress during early life may alter the developmental trajectory of an animal by a mechanism known as adaptive plasticity. For example, to enhance reproductive success in an adverse environment, it is known that animals accelerate their growth during development. However, these short-term fitness benefits are often associated with reduced longevity, a phenomenon known as the growth rate-lifespan trade-off. In humans, early life stress exposure compromises health later in life and increases disease susceptibility. Glucocorticoids (GCs) are major stress hormones implicated in these processes. This Review discusses the evidence for GC-mediated adaptive plasticity in development, leading to allostatic overload in later life. We focus on GC-induced effects on brain structure and function, including neurogenesis; highlight the need for longitudinal studies; and discuss approaches to identify molecular mechanisms mediating GC-induced alteration of the brain developmental trajectory leading to adult dysfunctions. Further understanding of how stress and GC exposure can alter developmental trajectories at the molecular and cellular level is of critical importance to reduce the burden of mental and physical ill health across the life course.

Keywords: Allostasis; Cortisol; Neurodevelopment; Neurogenesis; Phenotypic plasticity; Stress.

Fig. 1.

Model proposing that elevated glucocorticoid (GC) mediates adaptive plasticity during development leading to allostatic overload in later life. We suggest that in the short term, exposure to high levels of GCs can drive adaptive developmental plasticity, such as increased growth, accelerated maturation and enhanced behavioural performance. However, over time, chronic GC exposure leads to an accumulation of allostatic load, ultimately leading to a maladaptive state of allostatic overload. Allostatic overload may manifest via accelerated aging, reduced longevity and behavioural disorders in later life. Figure adapted from Eachus et al. (2023a preprint).