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Neonatal maternal separation impairs cognitive function and synaptic plasticity in adult male CD-1 mice
Zhen-Yu Hu1, Ru-Meng Wei2, Fei-Hu2
1The Affiliated Chaohu Hospital of Anhui Medical University, Hefei, Anhui 238000, China.
Insights
Maternal separation in mice leads to anxiety, depression, and impaired memory. These cognitive deficits are linked to changes in synaptic plasticity proteins and function.
Area of Science:
- Neuroscience
- Developmental Psychology
- Molecular Biology
Background:
- Maternal separation (MS) is a known risk factor for anxiety, depression, and cognitive impairments in offspring.
- The precise molecular mechanisms underlying these long-term effects of MS remain largely unknown.
Purpose of the Study:
- To investigate the behavioral and molecular consequences of maternal separation in adult mice.
- To explore the impact of MS on synaptic plasticity and related protein expression.
Main Methods:
- Maternal separation was performed on CD-1 mice from postnatal day 4 to 21.
- Behavioral tests assessed anxiety, depression, and spatial learning and memory.
- Western blotting and RT-PCR analyzed protein and gene expression (BDNF, TrkB, PSD-95, SYNP).
- Electrophysiology recorded long-term potentiation (LTP), long-term depression (LTD), and miniature excitatory postsynaptic currents (mEPSCs).
Main Results:
- Maternal separation induced anxiety- and depression-like behaviors and impaired spatial learning and memory in adult mice.
- MS significantly altered synaptic plasticity, impairing LTP and enhancing LTD at Schaffer collateral/CA1 synapses.
- A reduction in the frequency of miniature excitatory postsynaptic currents (mEPSCs) was observed in CA1 pyramidal neurons.
Conclusions:
- Maternal separation negatively impacts offspring behavior, leading to anxiety, depression, and cognitive deficits.
- These behavioral changes are associated with significant alterations in synaptic plasticity and the expression of key synaptic proteins.
- The study highlights the critical role of early-life experiences in shaping long-term neural function and behavior.
Abstract:
Maternal separation (MS) increases the risk of occurrence of anxiety, depression, and learning and memory impairment in offspring. However, the underlying molecular biological mechanisms remain unclear. In the current study, offspring CD-1 mice were separated from their mothers from postnatal day 4 to postnatal day 21. At 3 months of age, the male offspring were selected for the evaluation of anxiety- and depression-like behaviors and learning and memory function. Western blotting and RT-PCR were used to examine the expression levels of brain-derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density-95, and synaptophysin. Long-term potentiation (LTP) and long-term depression (LTD) were recorded at Schaffer collateral/CA1 synapses. Furthermore, basal synaptic transmission was evaluated via the recording of the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs). The results showed that adult offspring CD-1 mice displayed anxiety- and depressive-like behaviors as well as impaired spatial learning and memory abilities. Electrophysiological analysis indicated that MS impaired LTP, enhanced LTD, and reduced the frequency of mEPSCs in pyramidal neurons in the CA1 region. Our findings suggested that MS can lead to anxiety, depression, and cognitive deficits, and these effects are associated with alterations in the levels of synaptic plasticity-associated proteins, consequently, also synaptic plasticity.
