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Published on: August 13, 2015
Early-Life Stress Induced by Neonatal Maternal Separation Leads to Intestinal 5-HT Accumulation and Causes Intestinal
Ding Yang1, Rulan Bai1, Chengzhong Li2
1College of Veterinary Medicine, China Agricultural University, Beijing, People's Republic of China.
Insights
Early life stress, like neonatal maternal separation, increases serotonin (5-HT) in mice, disrupting gut function. Inhibiting 5-HT offers potential therapeutic benefits for gastrointestinal disorders.
Area of Science:
- Neurogastroenterology
- Developmental Psychology
- Molecular Biology
Background:
- Early childhood stress is linked to gastrointestinal disorders like IBS.
- Neonatal maternal separation (NMS) in rodents models IBS-like bowel dysfunction.
- Serotonin (5-HT) regulates intestinal function, but mechanisms are unclear.
Purpose of the Study:
- To investigate 5-HT expression and mechanisms in a mouse model of early life stress.
- To explore 5-HT's role in stress-induced gut dysfunction.
- To identify potential therapeutic targets for IBS.
Main Methods:
- Established a maternal separation stress mouse model.
- Measured 5-HT expression patterns under chronic stress.
- Investigated the effects of 5-HT inhibition on gut function and neurogenesis.
Main Results:
- NMS significantly increased 5-HT expression, causing intestinal dysfunction.
- Inhibiting 5-HT reversed NMS-induced gut changes.
- Excess 5-HT increased intestinal neural network density and motor neuron expression.
- 5-HT activated the Wnt pathway via the 5-HT4 receptor, promoting neurogenesis.
Conclusions:
- Early life stress induces significant intestinal changes mediated by 5-HT.
- 5-HT plays a key regulatory role in the enteric nervous system.
- Targeting 5-HT pathways may offer novel therapies for stress-related gastrointestinal disorders.
Background:
The early childhood period is a critical development stage, and experiencing stress during this time may increase the risk of gastrointestinal disorders, including irritable bowel syndrome (IBS). Neonatal maternal separation (NMS) in rodent models has been shown to cause bowel dysfunctions similar to IBS, and 5-HT is considered to be a key regulator regulating intestinal function, but the precise underlying mechanisms remain unclear.
Results:
We established a maternal separation stress mouse model to simulate early-life stress, exploring the expression patterns of 5-HT under chronic stress and its mechanisms affecting gut function. We observed a significant increase in 5-HT expression due to NMS, leading to disruptions in intestinal structure and function. However, inhibiting 5-HT reversed these effects, suggesting its potential as a therapeutic target. Furthermore, our research revealed that excess 5-HT in mice with early life stress increased intestinal neural network density and promoted excitatory motor neuron expression. Mechanistically, 5-HT activated the Wnt signaling pathway through the 5-HT4 receptor, promoting neurogenesis within the intestinal nervous system.
Conclusion:
These findings shed light on the intricate changes induced by early life stress in the intestines, confirming the regulatory role of 5-HT in the enteric nervous system and providing potential insights for the development of novel therapies for gastrointestinal disorders.
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