Amyloid-beta (1-42) lesion of CA1 rat dorsal hippocampus reduces contextual fear memory and increases expression of microglial genes regulating neuroinflammation

Emerging evidence indicates that the pathogenesis of Alzheimer's disease (AD) is not confined to neuronal disruptions but robustly communicates with the brain's immune system. Genome-wide analysis suggests that several genes, which increase the risk for AD, encode for factors that regulate the glial clearance of misfolded proteins and the inflammatory reaction. This study reappraises the amyloid hypothesis by focusing on the impact of neuroinflammation in a beta-amyloid model of AD, how this possibly exacerbates the disease's progression, and the correlation between genes regulating neuroinflammation (CD33 and TREM2) with post-training recall. Male Sprague-Dawley rats were used for this study, randomly divided into a vehicle group of rats (n = 40) that were infused with phosphate-buffered saline (PBS) and an A beta((1-42)) group (n = 40) that were infused with the neurotoxin A beta((1-42)) peptide. Fear conditioning WA (FCT) to assess fear memory was conducted pre and postlesion. The polymerase chain reaction was performed to determine the expression levels of CD33 and TREM2 genes. Our results show that A beta((1-42)) lesion of the rat CAl hippocampal subregion significantly reduces contextual fear memory, and this reduction was exacerbated as the post-lesion days increased. We also observed an increase in the expression levels of CD33 and TREM2 genes in the A beta((1-42)) lesioned groups compared to their corresponding vehicle groups. Taken together, the behavioral and gene expression data provide inferential evidence that A beta((1-42)) infusion impairs contextual memory by disrupting cellular pattern separation processes in the hippocampus, thus linking neuroinflammation to specific neural circuit disruption and cognitive deficit.