Cortisol affects brain cells by binding to receptors in the brain, particularly in regions critical for cognition such as the hippocampus and prefrontal cortex. High or prolonged cortisol levels can have neurotoxic effects, including promoting oxidative stress, inflammation, and damaging brain cells, especially in the hippocampus, which may lead to atrophy of this memory-related brain region. Cortisol also alters neurotransmitter systems and synaptic functioning, impairing memory, executive function, and overall cognitive performance. Chronic elevated cortisol is linked to brain structural changes like decreased gray matter volume, microstructural white matter changes, and cognitive decline, thereby increasing the risk for dementia and Alzheimer's disease.
Mechanisms of Cortisol's Effects on Brain Cells:
- Cortisol acts through mineralocorticoid (MR) and glucocorticoid receptors (GR) in brain cells, producing complex effects on neurotransmission and synaptic plasticity.
- It promotes glutamate release, which leads to oxidative stress and free radical damage, harming brain cells.
- Cortisol interferes with brain-derived neurotrophic factor (BDNF), reducing its expression and contributing to neuronal atrophy.
- Activation of GR by cortisol can inhibit prefrontal cortex functions like working memory and impair long-term potentiation (LTP), vital for memory formation.
Structural and Cognitive Impact:
- Elevated cortisol is associated with decreased volumes in the hippocampus, frontal, and occipital gray matter.
- Chronic high cortisol leads to brain cell death in key areas responsible for memory and emotional regulation.
- There is evidence linking high cortisol with impaired memory, executive function, processing speed, and increased risk for neurodegenerative diseases.
- In women, higher cortisol correlates strongly with reductions in cerebral brain volume and cognitive deficits.
Summary:
Cortisol, especially when elevated chronically due to stress or disease, negatively affects brain cells by damaging their structure, altering neurotransmission, and reducing neuroplasticity, all of which can contribute to cognitive decline and increased risk for neurodegenerative disorders like Alzheimer's disease.
