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Updated: Jan 9, 2026
Evaluation of Synapse Density in Hippocampal Rodent Brain Slices
Published on: October 6, 2017
The early postnatal synapse assembly and expression profiles of synapse-related genes in a sporadic Alzheimer's
Natalia A Stefanova1, Kseniya Y Maksimova2, Mikhail A Tyumentsev1,3
1Institute of Cytology and Genetics, Novosibirsk, Russia.
Insights
Delayed brain maturation in OXYS rats, an Alzheimer's disease (AD) model, shows reduced synaptic density and altered gene expression, indicating impaired neural connections crucial for AD pathology.
Area of Science:
- Neuroscience
- Developmental Biology
- Pathology
Background:
- Alzheimer's disease (AD) pathology may originate during early development.
- OXYS rats model sporadic AD and exhibit developmental abnormalities.
Purpose of the Study:
- Investigate delayed brain maturation's role in later-life AD-like pathology in OXYS rats.
- Analyze synaptic development and gene expression in early life stages.
Main Methods:
- Assessed synaptic density and gene expression profiles in prefrontal cortex (PFC) and hippocampus.
- Compared OXYS rats with Wistar rats from postnatal day 0 (P0) to P20.
- Utilized transcriptome analysis and cell-specific gene expression profiling.
Main Results:
- OXYS rats had 50% less synaptic population in the PFC at birth compared to Wistar rats.
- Hippocampal synaptic development in OXYS rats was delayed by approximately 7-14 days.
- Transcriptome analysis revealed distinct synaptic gene expression profiles and identified age- and region-specific genes.
- Over 50% of downregulated genes in OXYS rats were associated with glial cells.
Conclusions:
- Data indicate a significant delay in interneuronal connection formation and efficiency in OXYS rats.
- This developmental delay in synaptic maturation may contribute to AD-like pathology.
- Glial cell dysfunction appears to play a critical role in the observed synaptic deficits.
Abstract:
BackgroundRecent evidence suggests that prerequisites for Alzheimer's disease (AD) can form during prenatal and early postnatal development. These prerequisites have been identified to some extent in OXYS rats: a model of the sporadic form of AD.ObjectiveHere, we continue to study the role of delayed brain maturation in the development of the AD-like pathology much later in OXYS rats.MethodsWe assess synaptic-density changes and gene expression profiles in the prefrontal cortex (PFC) and hippocampus of OXYS and Wistar rats (parental strain; control) between ages "postnatal day 0" (P0) and P20.ResultsWe found that at birth, the synaptic population in the PFC of OXYS rats is half of that in Wistar rats. The proportion of both symmetric (inhibitory) contacts and asymmetric (excitatory) contacts in the hippocampus of OXYS rats at P14 and P20 matched these parameters in Wistar rats at P7 and P14, respectively. The transcriptome analysis of the PFC and hippocampus showed that gene expression profiles related to synapses are different between Wistar and OXYS rats. Next, we identified "age-specific" genes and "brain region-specific" genes whose changes in the expression can obviously contribute to the specific features of synapse formation in OXYS rats. Finally, analyses of cell-specific (neurons, astrocytes, microglia, oligodendrocytes, and endothelial cells) gene expression suggested that at P3-P20 in the PFC and hippocampus, more than 50% of downregulated genes are associated with glia: key regulators of neural-network functioning.ConclusionsCollectively, these data indicate a delay in the formation of interneuronal connections and in their efficiency in the OXYS strain.
