Advanced maternal age impairs synaptic plasticity in offspring rats
Wei Han1, Ya' Nan Pan1, Ziyao Han1
1Department of Neurology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, No.136 Zhongshan 2nd Road, Chongqing 400014, China.
Insights
Advanced maternal age (AMA) in rats is linked to impaired synaptic plasticity in offspring, potentially explaining neurodevelopmental issues. This study found reduced synapse proteins and altered brain function in offspring born to older mothers.
Area of Science:
- Neuroscience
- Developmental Biology
- Reproductive Science
Background:
- Advanced maternal age (AMA) is increasingly common and linked to adverse neurodevelopmental outcomes in children.
- Synaptic plasticity is crucial for neurocognitive and emotional development.
Purpose of the Study:
- To investigate the impact of AMA on synaptic structure and function in offspring.
- To explore the potential mechanisms linking AMA to neurodevelopmental disorders.
Main Methods:
- Comparison of offspring from aged (12-month) and young (3-month) Sprague-Dawley rats.
- Analysis of synaptic ultrastructure, key synapse-related proteins (NF200, PSD-95, SYP), and long-term potentiation (LTP).
- Techniques included immunofluorescence, Western blot, transmission electron microscopy, and electrophysiology.
Main Results:
- Offspring of AMA rats showed reduced neurofilament 200 (NF200) and axon length at postnatal day 14.
- Decreased expression of postsynaptic density-95 (PSD-95) and synaptophysin (SYP) was observed in AMA offspring at postnatal day 7.
- Ultrastructural analysis revealed altered postsynaptic density (PSD) thickness and active zone (AZ) length.
- Impaired long-term potentiation (LTP) was evident in the hippocampus of AMA offspring.
Conclusions:
- Advanced maternal age negatively impacts synaptic plasticity in offspring.
- These synaptic alterations may contribute to the neurodevelopmental disorders associated with AMA.
Abstract:
Advanced maternal age (AMA) has become more common in the last decade and is associated with poor neurodevelopmental outcomes in offspring. Neurocognitive and emotional development is associated with synaptic structural and functional plasticity. In the present study, we investigated the relationship between AMA and synapse plasticity in the offspring. We examined the synaptic ultrastructure, synapse-related proteins and long-term potentiation (LTP) in the offspring of Sprague-Dawley female rats aged 12 months (AMA group) and 3 months (Control group) on postnatal (P) days 7, 14, 28 and 60. Immunofluorescence analysis revealed decreases in the expression of neurofilament 200 (NF200) and axon length in the AMA group compared with the control group at P14. Western blot analysis showed that the expression of postsynaptic density-95 (PSD-95) and synaptophysin (SYP) was reduced in the immature offspring of the AMA group at P7. Transmission electron microscopy showed decreased thickness of the PSD and increased length of the active zone (AZ) in the offspring of the AMA group. Electrophysiological recordings in hippocampal slices revealed impaired LTP in the AMA offspring. Our data suggest that AMA impairs the synaptic plasticity of offspring, which may underlie the mechanism of neurodevelopmental disorders.
