Stress Impairs PFC: How Do Signaling Pathways Affect Brain Function?

Author Names:

Amy F. T. Arnsten

Published Date: June 2009

Source: Nature Reviews Neuroscience

Abstract: 

The prefrontal cortex (PFC) regulates our highest-order cognitive abilities but is highly sensitive to stress. This paper reviews how stress impacts PFC functions, leading to cognitive deficits and structural changes. It explores the intracellular signalling pathways involved and discusses how these findings can help us understand mental illnesses and potential treatments.

Key Concepts:

• Prefrontal Cortex (PFC): A brain region responsible for executive functions, decision-making, and emotional regulation.
• Stress Signaling Pathways: Pathways activated by stress that affect neuronal function and structure.
• Glucocorticoid Signaling: Hormonal pathways activated during stress, influencing neuronal plasticity.
• Glutamatergic Signaling: Involves neurotransmitters critical for synaptic plasticity and cognitive functions.
• Literature Review: Previous studies indicate that stress impairs PFC functions by disrupting neuronal connections and reducing dendritic branching.

Procedure Highlight - Research Methodology:

1. Human Studies: Review of studies examining the effects of acute and chronic stress on cognitive functions and PFC activity.
2. Animal Models: Experiments using rodents to investigate the impact of stress on PFC structure and function.
3. Data Collection: Behavioral tests assessed cognitive functions, while histological analyses examined changes in neuronal structure.
4. Analysis: Evaluation of the effects of stress on PFC structure and function using statistical methods.

Results - Findings of Research:

• Acute Stress Effects: Acute stress rapidly impairs PFC functions, reducing cognitive flexibility and working memory in humans and animals.
• Chronic Stress Effects: Prolonged stress leads to structural changes in the PFC, such as dendritic retraction, reducing cognitive abilities.
• Intracellular Signalling: High levels of stress hormones like noradrenaline and dopamine alter intracellular pathways (e.g., cAMP-PKA, PKC), impairing PFC neuron function.
• Genetic and Environmental Factors: Genetic variations and environmental insults like trauma or toxins can exacerbate stress signalling, further impairing PFC function and contributing to mental illnesses.

Discussion and Conclusion: 

This study elucidates how stress impacts PFC function through specific signalling pathways, leading to cognitive deficits and structural changes. Understanding these mechanisms is crucial for developing better treatments for stress-related mental illnesses.

For example, targeting specific receptors or signalling pathways might help restore PFC function in affected individuals. The research highlights the importance of managing stress to maintain cognitive health and prevent mental illness.

PMC Link: Stress signalling pathways that impair prefrontal cortex structure and function

Author Information

Amy F. T. Arnsten: Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut, USA

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