The pathological process where sustained, excessive exposure to the primary glucocorticoid, cortisol, results in measurable damage or functional destruction of neurons within the central nervous system. This is a significant concern in states of chronic HPA axis hyperactivity, often manifesting as hippocampal atrophy and associated cognitive deficits. The process involves direct excitotoxic effects on neuronal structure and function over prolonged periods of hypercortisolemia. Clinically, it represents a critical endpoint of chronic stress signaling that compromises neural tissue maintenance.
Origin
This term combines the endocrine stress mediator, cortisol, with the neurological outcome, neurodegeneration, reflecting established research demonstrating the toxicity of high glucocorticoid levels. The implication is that prolonged exposure tips the balance from normal, adaptive glucocorticoid signaling to outright cellular injury and loss of neural connectivity. It frames chronic stress as a direct neurotoxic process.
Mechanism
High cortisol concentrations can induce neuronal damage through several distinct pathways, including promoting excitotoxicity via dysregulation of $text{NMDA}$ receptor function and increasing intracellular oxidative stress burdens within the neuron. Furthermore, sustained activation of glucocorticoid receptors can suppress the necessary expression of neurotrophic factors, such as Brain-Derived Neurotrophic Factor ($text{BDNF}$), which are required for neuronal survival and plasticity. Apoptosis is often triggered in sensitive regions, particularly the hippocampus, following prolonged exposure to supra-physiological cortisol levels.
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