Related Experiment Video
Updated: May 31, 2026
An Unpredictable Chronic Mild Stress Protocol for Instigating Depressive Symptoms, Behavioral Changes and Negative Health Outcomes in Rodents
Published on: December 2, 2015
Research on the Mechanisms Involving Endoplasmic Reticulum Stress in the Comorbidity of Atopic Dermatitis and
Heng Chai1, Jing Zhou1, Yuge Gao1
1Department of Dermatology and Venereology, The Second Affiliated Hospital of Harbin Medical University, 150086 Harbin, Heilongjiang, China.
Objective:
This study aimed to investigate the role of endoplasmic reticulum stress (ERS) in atopic dermatitis (AD) and its comorbid mental disorders and evaluate the therapeutic potential of mesencephalic astrocyte-derived neurotrophic factor (MANF).
Methods:
Clinical samples from patients with AD and comorbidities were analyzed for ERS and apoptosis markers using quantitative polymerase chain reaction and western blotting. Mouse models of depression were developed using 28 days of chronic unpredictable mild stress (CUMS), and dermatitis was induced using 0.2% 2,4-dinitrofluorobenzene. Adenovirus-mediated MANF overexpression was induced via local injection to develop comorbidities, comorbidities + negative control overexpression, and comorbidities + MANF overexpression groups. Further, the ERS inhibitors of 4-phenylbutyric acid were employed for the comorbidities + inhibitors group. Dermatitis scoring, the sucrose preference test for behavioral changes, and ERS and apoptosis assessments using transmission electron microscopy, terminal deoxynucleotidyl transferase dUTP Nick-End labeling staining, hematoxylin and eosin staining, and immunohistochemistry were conducted.
Results:
Clinical data demonstrated significant increases in ERS-related markers (GRP78, P-IRE1, and Caspase-12) and apoptosis marker of Bax, whereas Bcl-2 was decreased in comorbidities compared with those with AD alone. In mouse models, increased Bax and decreased Bcl-2 indicated apoptotic pathway activation in the comorbidities group. MANF overexpression reduced ERS-related factors and skin pathology while improving behavioral indicators. Further, MANF reduced skin cell apoptosis by downregulating Bax and upregulating Bcl-2. ERS inhibitors similarly alleviated cell apoptosis, thereby confirming the critical role of ERS in disease progression.
Conclusion:
MANF overexpression reduces ERS and apoptosis, which improves AD symptoms and comorbid mental disorders, thereby highlighting its therapeutic target potential.
Related Concept Videos
01:27Psychoneuroimmunology: Cardiovascular Disease
A key area of focus in PNI is the relationship between stress and coronary...
01:17Role of ER in the Secretory Pathway
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
01:30Stress and Mental Health
Individuals with depression often experience challenges in both their personal and professional...
01:27Depressive Disorders: Etiology
Biological Factors in Depression
Biological predispositions significantly influence the risk of developing depressive disorders. Genetic studies highlight the role of variations in the serotonin transporter...
01:29Psychological and Sociocultural Causes of Schizophrenia
01:21Smooth Endoplasmic Reticulum
The ER provides optimal conditions for synthesizing steroid hormones and lipids, such as phospholipids and triglycerides. Traditionally, lipid metabolism was considered to be a smooth ER function. However, there is no direct evidence to prove that rough ER is completely excluded from lipid...