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Review
. 2025:291:339-361.
doi: 10.1016/bs.pbr.2025.01.018. Epub 2025 Feb 17.

Models developed to explain the effects of stress on brain and behavior

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Review

Models developed to explain the effects of stress on brain and behavior

Adejoke Elizabeth Memudu et al. Prog Brain Res. 2025.

Abstract

There is an integral relationship between stress, brain function and behavior. Over the year's extensive research has led to the development of various models to explain the intricate intersection between brain and stress. This chapter delves into some of the theoretical frameworks that explains the neurobiological and behavioral responses to stress using key models of stress such as the allostatic load model, which is the most common model that describes how chronic stress affect brain structure and function resulting in long-term changes in regions such as the hippocampus, amygdala, and prefrontal cortex which phenotypically express as cognitive impairments, emotional dysfunction seen in various forms of neurological disorder. The neuro-endocrine model, follows the glucocorticoid cascade hypothesis, that associates prolonged stress exposure to hippocampal damage and cognitive decline via alteration in the hypothalamic-pituitary-adrenal (HPA) axis and the overproduction of stress hormones like cortisol which can induce hippocampal atrophy, impair learning and memory, and promote depressive-like behaviors. The neurobiological stress model addresses the role of the hypothalamic-pituitary-adrenal (HPA) axis and stress-related neurotransmitters in shaping behavioral responses, emphasizing alterations in neuroplasticity and synaptic function. These models demonstrate how chronic stress can alter neural plasticity, neurotransmitter systems, and synaptic connectivity, affecting behavior and cognitive function. Hence by integrating molecular, neurobiological, and behavioral perspectives, these models offer a comprehensive understanding of how stress alters brain activity and behavior. The chapter further showcase how these models direct the development of medical interventions, shedding light on potential therapies that target the underlying molecular mechanisms of stress-induced brain changes.

Keywords: Behavior; Brain; Cognitive impairments; Hypothalamic-pituitary-adrenal (HPA) axis; Neuroplasticity; Neurotransmitters; Stress model.

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