Related Experiment Video
Updated: Jul 22, 2026
A Chronic Immobilization Stress Protocol for Inducing Depression-Like Behavior in Mice
Published on: May 15, 2019
Restructuring the neuronal stress response with anti-glucocorticoid gene delivery
D Kaufer1, W O Ogle, Z S Pincus
1Department of Biological Sciences, Stanford University, Stanford, California, USA. danielak@stanford.edu
Abstract:
Glucocorticoids, the adrenal steroids released during stress, compromise the ability of neurons to survive neurological injury. In contrast, estrogen protects neurons against such injuries. We designed three genetic interventions to manipulate the actions of glucocorticoids, which reduced their deleterious effects in both in vitro and in vivo rat models. The most effective of these interventions created a chimeric receptor combining the ligand-binding domain of the glucocorticoid receptor and the DNA-binding domain of the estrogen receptor. Expression of this chimeric receptor reduced hippocampal lesion size after neurological damage by 63% and reversed the outcome of the stress response by rendering glucocorticoids protective rather than destructive. Our findings elucidate three principal steps in the neuronal stress-response pathway, all of which are amenable to therapeutic intervention.
Insights
Glucocorticoids harm neurons during stress, but a new chimeric receptor strategy protected them. This genetic intervention reversed stress effects, making glucocorticoids beneficial for neuronal survival after injury.
Area of Science:
- Neuroscience
- Endocrinology
- Genetics
Background:
- Glucocorticoids, released during stress, impair neuronal survival after neurological injury.
- Estrogen, conversely, exhibits neuroprotective properties.
- The neuronal stress-response pathway presents therapeutic intervention targets.
Purpose of the Study:
- To develop genetic interventions mitigating the detrimental effects of glucocorticoids on neurons.
- To investigate the potential of manipulating glucocorticoid receptor actions for neuroprotection.
Main Methods:
- Three distinct genetic interventions were designed to alter glucocorticoid receptor signaling.
- In vitro and in vivo rat models of neurological injury were utilized.
- A chimeric receptor, combining glucocorticoid and estrogen receptor domains, was engineered and tested.
Main Results:
- The most effective intervention involved a chimeric receptor combining glucocorticoid receptor ligand-binding and estrogen receptor DNA-binding domains.
- Expression of this chimeric receptor significantly reduced hippocampal lesion size by 63% post-injury.
- Glucocorticoids were rendered neuroprotective, reversing their destructive role in the stress response.
Conclusions:
- Genetic manipulation of the glucocorticoid receptor can effectively protect neurons against stress-induced injury.
- The developed chimeric receptor represents a promising therapeutic strategy for neurological damage.
- Understanding the neuronal stress-response pathway opens avenues for novel neuroprotective treatments.
More Related Videos
10:50Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons
Published on: April 24, 2021
05:17BS3 Chemical Crosslinking Assay: Evaluating the Effect of Chronic Stress on Cell Surface GABAA Receptor Presentation in the Rodent Brain
Published on: May 26, 2023