Prenatal Stress Impairs Postnatal Learning and Memory Development via Disturbance of the cGMP-PKG Pathway and
Yu-Jie Li1, Li-Ping Yang2, Jun-Lin Hou2
1Pharmacology Laboratory, School of Basic Medical Medicine, Henan University of Chinese Medicine, Zhengzhou, China.
Insights
Prenatal stress in rats caused growth and memory deficits in offspring. This was linked to altered hippocampal proteins, impaired energy metabolism, and inhibited cyclic guanosine monophosphate-protein kinase G (cGMP-PKG) signaling.
Area of Science:
- Neuroscience
- Developmental Biology
- Molecular Biology
Background:
- Prenatal stress is linked to fetal pathological changes, but underlying mechanisms remain unclear.
- Understanding these mechanisms is crucial for addressing developmental impacts of maternal stress.
Purpose of the Study:
- To investigate the effects of chronic psychological stress during pregnancy on offspring behavior and hippocampal proteome.
- To elucidate the molecular pathways involved in prenatal stress-induced neurodevelopmental alterations.
Main Methods:
- Pregnant rats exposed to chronic psychological stress using a communication box system.
- Analysis of offspring behavioral performance, spatial learning, and memory.
- Proteomics analysis (isobaric tags for relative and absolute quantitation) of hippocampal tissue.
- Pathway enrichment analysis to identify affected biological processes and signaling cascades.
Main Results:
- Prenatal stress resulted in postnatal growth retardation and impaired spatial learning and memory in offspring.
- 158 differentially expressed proteins (DEPs) identified in the hippocampus, involved in energy metabolism, learning, memory, and synaptic plasticity.
- Impaired learning and memory correlated with the cyclic guanosine monophosphate-protein kinase G (cGMP-PKG) pathway and oxidative phosphorylation.
- Decreased cGMP levels, reduced PKG protein expression, and mitochondrial abnormalities observed in the hippocampus.
Conclusions:
- Chronic prenatal stress negatively impacts offspring neurodevelopment, leading to cognitive deficits.
- Alterations in hippocampal oxidative phosphorylation and cGMP-PKG pathway are key mechanisms mediating these effects.
- Maternal stress during gestation poses a significant risk for offspring brain development and function.
Abstract:
Clinical and animal studies have found that prenatal stress can lead to pathological changes in embryos and fetuses. However, the mechanisms through which this occurs have not been made clear. In the present study, pregnant rats were subjected to chronic psychological stress during gestational days using an improved communication box system, and the changes in behavioral performance and proteins in the hippocampus of offspring were analyzed. It was found that prenatal stress caused postnatal growth retardation and impairment in spatial learning and memory. Furthermore, in isobaric tags for relative and absolute quantitation-based proteomics analyses, 158 significantly differentially expressed proteins (DEPs) were found between the two groups. Further analyses showed that these DEPs are involved in different molecular function categories and participate in several biological processes, such as energy metabolism, learning or memory, and synaptic plasticity. Moreover, the enrichment of pathways showed that the learning and memory impairment was primarily connected with the cyclic guanosine monophosphate-protein kinase G (cGMP-PKG) pathway and oxidative phosphorylation. At the same time, the cGMP level and the expression of PKG protein were significantly decreased, and the neuronal mitochondria appeared to have a swollen and irregular shape in the hippocampus of offspring of stressed rats. These results suggest that the chronic psychological stress that pregnant rats were subjected to during gestational days may have impaired the spatial learning and memory of offspring. This affected the hippocampal oxidative phosphorylation and inhibited the cGMP-PKG pathway.
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