The early postnatal synapse assembly and expression profiles of synapse-related genes in a sporadic Alzheimer's disease-like pathology

Abstract

Background

Recent 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.

Objective

Here, we continue to study the role of delayed brain maturation in the development of the AD-like pathology much later in OXYS rats.

Methods

We 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.

Results

We 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.

Conclusions

Collectively, these data indicate a delay in the formation of interneuronal connections and in their efficiency in the OXYS strain.