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The involvement of ERK/CREB/Bcl-2 in depression-like behavior in prenatally stressed offspring rats
Lixia Guan1, Ning Jia, Xiaoyan Zhao
1Department of Pharmacology, College of Medicine, Xi'an Jiaotong University, China.
Insights
Prenatal stress (PS) in rats increases depression-like behaviors and alters ERK-CREB signaling in offspring brains. These effects may involve NMDA receptors, suggesting a pathway for future interventions.
Area of Science:
- Neuroscience
- Molecular Biology
- Behavioral Science
Background:
- Prenatal stress (PS) is linked to increased depression vulnerability in offspring.
- The extracellular signal-regulated kinase (ERK)-cyclic AMP responsive element binding protein (CREB) pathway is implicated in depression.
- Understanding PS effects on offspring neurobiology is crucial for developing interventions.
Purpose of the Study:
- To investigate the impact of prenatal restraint stress on depression-like behavior in juvenile rats.
- To examine the expression of ERK2, CREB, and Bcl-2 mRNA in key brain regions following PS exposure.
- To explore the role of the ERK-CREB pathway and NMDA receptors in mediating PS-induced behavioral changes.
Main Methods:
- Prenatal restraint stress was applied to Sprague-Dawley rats.
- Depression-like behavior was assessed using the forced swimming test in one-month-old offspring.
- Expression levels of ERK2, CREB, and Bcl-2 mRNA were quantified in the hippocampus, prefrontal cortex, and striatum.
- The effects of MK-801, an NMDA receptor antagonist, were evaluated.
Main Results:
- PS significantly increased immobility time, indicating depression-like behavior.
- PS decreased ERK2, CREB, and Bcl-2 mRNA expression in the hippocampus and prefrontal cortex.
- These PS-induced changes were partially reversed by MK-801 treatment.
- CREB expression in the hippocampus of male offspring was an exception, showing no significant decrease.
Conclusions:
- The ERK-CREB signaling pathway is implicated in the development of depression-like behaviors following prenatal stress.
- NMDA receptors may play a role in mediating the neurobiological effects of prenatal stress.
- These findings highlight potential therapeutic targets for addressing depression linked to prenatal stress exposure.
Abstract:
A number of studies reveal that prenatal stress (PS) may induce an increased vulnerability to depression in offspring. Some evidences indicate that extracellular signal-regulated kinase (ERK)-cyclic AMP responsive element binding protein (CREB) signal system may play an important role in the molecular mechanism of depression. In the present study, we examined the effects of prenatal restraint stress on depression-like behavior in one-month offspring Sprague-Dawley rats and expression of ERK2, CREB, B-cell lymphoma-2 (Bcl-2) mRNA in the hippocampus, prefrontal cortex and striatum to explore the potential role of ERK-CREB pathway in mediating the behavioral effects of PS exposure. Our findings demonstrated that PS increased immobility time in forced swimming test and decreased expression of ERK2, CREB, Bcl-2 mRNA in the hippocampus and prefrontal cortex of juvenile offspring rats except for CREB in hippocampus of male offspring. Changes induced by PS were partly prevented by MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist. These findings suggested that the ERK-CREB system might be related with the depression-like behavior in juvenile offspring rats subjected to PS, in which NMDA receptors might be involved.

