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Melatonin Alleviates Behavioral and Neurodevelopmental Abnormalities in Offspring Caused by Prenatal Stress
Dong Wu1, Jingyi Du1, Tiantian Zhao1
1Key Laboratory for Experimental Teratology of Ministry of Education, Shandong Key Laboratory of Mental Disorders and Intelligent Control, Department of Anatomy and Histoembryology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
Insights
Melatonin (Mel) can protect offspring from prenatal stress (PNS) by improving neurodevelopment and behavior. This neuroprotective effect is achieved by modulating microglial pathways and enhancing hippocampal function.
Area of Science:
- Neuroscience
- Pharmacology
- Developmental Biology
Background:
- Prenatal stress (PNS) is a risk factor for lifelong health issues, linked to neurodevelopmental and psychiatric disorders.
- Limited pharmacological interventions exist for PNS-induced detrimental effects.
- Melatonin (Mel), an endogenous hormone, offers neuroprotection with anti-inflammatory and antioxidant properties.
Purpose of the Study:
- Investigate melatonin's protective effects on neurodevelopmental and behavioral abnormalities in offspring exposed to prenatal stress.
- Elucidate the underlying mechanisms of melatonin's action.
Main Methods:
- Utilized a prenatal stress mouse model to assess melatonin's impact on offspring.
- Evaluated emotional and cognitive deficits, neurogenesis, and synaptic development.
- Employed RNA sequencing to analyze microglial gene expression and immune pathways, with in vivo and in vitro validation of the PI3K/AKT/NF-κB signaling pathway.
Main Results:
- Melatonin alleviated emotional and cognitive deficits in offspring exposed to prenatal stress.
- Observed improvements in neurogenesis and synaptic development.
- Melatonin suppressed microglial activation and immune-related pathways, modulating the PI3K/AKT/NF-κB pathway and reducing CXCL10 expression in the dentate gyrus.
Conclusions:
- Melatonin significantly improves neurodevelopmental and behavioral outcomes in offspring affected by prenatal stress.
- Inhibits pathological microglial activation and promotes hippocampal neurogenesis and synaptic plasticity.
- Highlights melatonin's potential as a neuroprotective agent for prenatal stress-related disorders.
Background:
Prenatal stress (PNS) is a significant risk factor impacting the lifelong health of offspring, and it has been widely recognized as being closely linked to the increased prevalence of neurodevelopmental disorders and psychiatric illnesses. However, effective pharmacological interventions to mitigate its detrimental effects remain limited. Melatonin (Mel), an endogenous hormone, has demonstrated considerable potential in treating neurological diseases due to its anti-inflammatory, antioxidant, and neuroprotective properties, as well as its favorable safety profile and broad clinical applicability.
Objective:
This study aims to investigate the protective effects and mechanisms of melatonin on neurodevelopmental and behavioral abnormalities in offspring induced by prenatal stress.
Methods:
Using a prenatal stress mouse model, we evaluated the effects of melatonin on emotional and cognitive deficits in offspring. Neurogenesis and synaptic development were assessed, and RNA sequencing was performed to analyze microglial gene enrichment and immune-related pathways. Both in vivo and in vitro experiments were conducted to validate the findings, focusing on the PI3K/AKT/NF-κB signaling pathway in microglia.
Results:
Melatonin administration alleviated emotional and cognitive deficits in offspring mice exposed to prenatal stress, addressing abnormalities in neurogenesis and synaptic development. Additionally, RNA sequencing revealed that melatonin suppresses microglial gene enrichment and the upregulation of immune-related pathways. Both in vivo and in vitro validation indicated that melatonin modulates the PI3K/AKT/NF-κB signaling pathway in microglia, reducing the elevated expression of CXCL10 in the dentate gyrus, thereby restoring normal neuro-supportive functions and optimizing the neurodevelopmental environment.
Conclusion:
These findings suggest that melatonin significantly improves neurodevelopmental disorders and behavioral abnormalities caused by prenatal stress by inhibiting pathological microglial activation and promoting hippocampal neurogenesis and synaptic plasticity. This provides new insights into melatonin's potential as a neuroprotective agent for treating prenatal stress-related disorders.
