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Related Concept Videos

Hypothalamic-Pituitary Axis01:37

Hypothalamic-Pituitary Axis

The response to stress—be it physical or psychological, acute or chronic—involves activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis. The HPA axis is part of the neuroendocrine system because it involves both neuronal and hormonal communication. Its function is to regulate homeostatic systems—metabolic, cardiovascular, and immune—providing the necessary means to respond to a stressor.
Physiological Foundation of Stress01:24

Physiological Foundation of Stress

Stress triggers a coordinated physiological response involving the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis. This dual activation ensures that the body is prepared for both immediate and prolonged stress management. The process begins with the perception of a stressor. This initial phase activates the SNS, leading to the rapid release of adrenaline (epinephrine) from the adrenal glands.
Role of the Sympathetic Nervous System
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Psychological Responses to Stress01:20

Psychological Responses to Stress

Psychological responses to stress encompass the various cognitive and emotional reactions individuals experience when faced with challenging or threatening situations, such as a job loss. Prolonged exposure to stressors can disturb emotional balance, increasing negative emotions (e.g., anxiety and sadness) and diminishing positive emotions (e.g., joy and satisfaction). These persistent emotional shifts are associated with an increased risk of both physical illness and mental health issues, such...
Stress Response System01:21

Stress Response System

The stress response system, also known as the fight-or-flight response, is the body's automatic physiological reaction to perceived threats. Hans Selye introduced the concept of General Adaptation Syndrome (GAS) to describe the predictable pattern of changes that occur in response to stress. GAS consists of three sequential stages: alarm, resistance, and exhaustion. This model helps explain how chronic stress can contribute to health problems.
Alarm stage
In the alarm stage, the body's initial...
Psychoneuroimmunology: Diabetes and Cancer01:19

Psychoneuroimmunology: Diabetes and Cancer

Chronic stress has been linked to both the onset and progression of serious health conditions, including Type 2 diabetes and cancer. Type 2 diabetes, a widespread chronic illness, is closely associated with obesity and insulin resistance, both of which often worsen under stress. Studies indicate that men experiencing high levels of chronic stress face a 45% higher risk of developing diabetes compared to those with minimal stress. Stress triggers physiological responses that elevate blood...
Psychoneuroimmunology: Cardiovascular Disease01:27

Psychoneuroimmunology: Cardiovascular Disease

Psychoneuroimmunology (PNI) is a multidisciplinary field that examines how psychological factors, particularly stress, interact with the immune system and impact physical health. Research in PNI has shown that chronic or traumatic stress can disrupt both the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. These disruptions contribute to serious health conditions, including cardiovascular diseases.
A key area of focus in PNI is the relationship between stress and coronary...

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Related Experiment Video

Updated: Jul 16, 2026

A Chronic Immobilization Stress Protocol for Inducing Depression-Like Behavior in Mice
05:28

A Chronic Immobilization Stress Protocol for Inducing Depression-Like Behavior in Mice

Published on: May 15, 2019

Distinct cell type-specific mechanisms underlie cognitive dysfunction during persistent integrated stress response

Kristof Torkenczy1, Lucas C Reineke1, Sean W Dooling1

  • 1Altos Labs, Inc., Bay Area Institute, Redwood City, CA 94665.

Proceedings of the National Academy of Sciences of the United States of America
|July 14, 2026
PubMed
Summary

Persistent activation of the integrated stress response (ISR) drives cognitive decline. This study reveals cell-specific ISR mechanisms, showing GABAergic neurons are crucial for cognitive function in intellectual disability models.

Keywords:
cellular homoeostasiscognitive declinesingle-cell ATAC-sequencingsingle-cell RNA-sequencing

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08:29

Biomarkers in an Animal Model for Revealing Neural, Hematologic, and Behavioral Correlates of PTSD

Published on: October 10, 2012

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Persistent activation of the integrated stress response (ISR) is a key factor in cognitive decline associated with neurodevelopmental and neurodegenerative disorders.
  • The precise cell-type-specific mechanisms driving these cognitive deficits are not well understood.
  • Understanding these mechanisms is crucial for developing targeted therapeutic strategies.

Purpose of the Study:

  • To investigate the cell type-specific mechanisms of persistent ISR activation and its impact on cognitive function.
  • To create a comprehensive brain ISR atlas using a mouse model of intellectual disability.
  • To identify molecular signatures associated with ISR-mediated cellular vulnerability and cognitive dysfunction.

Main Methods:

  • Integration of single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq).
  • Utilized Ppp1r15bR658C mice, a model exhibiting selective and persistent ISR activation.
  • Performed selective deletion of the ISR effector ATF4 in specific neuronal subtypes (GABAergic and glutamatergic).

Main Results:

  • Distinct brain cell types exhibit differential engagement of transcriptional and chromatin remodeling programs in response to ISR activation.
  • Selective deletion of ATF4 in GABAergic neurons, but not glutamatergic neurons, worsened ISR-mediated cognitive decline.
  • A molecular single-cell signature of persistent ISR activation was defined, correlating with cellular vulnerability and cognitive dysfunction.

Conclusions:

  • Cell type-specific responses are critical drivers of cognitive dysfunction during persistent ISR activation.
  • Different neuronal subtypes rely on distinct ISR effectors, highlighting the complexity of neuronal regulation.
  • The identified ISR signature serves as a potential biomarker for cognitive dysfunction in human disorders.