RT-DOb, a switch gene for the gene pair {Csf1r, Milr1}, can influence the onset of Alzheimer’s disease by regulating communication between mast cell and microglia

Abstract

In biology, homeostasis is a central cellular phenomenon that plays a crucial role in survival. The central nervous system (CNS) is controlled by exquisitely sensitive homeostatic mechanisms when facing inflammatory or pathological insults. Mast cells and microglia play a crucial role in CNS homeostasis by eliminating damaged or unnecessary neurons and synapses. Therefore, decoding molecular circuits that regulate CNS homeostasis may lead to more effective therapeutic strategies that specifically target particular subsets for better therapy of Alzheimer’s disease (AD). Based on a computational analysis of a microarray dataset related to AD, theH2-Obgene was previously identified as a potential modulator of the homeostatic balance between mast cells and microglia. Specifically, it plays such a role in the presence of a three-way gene interaction in which theH2-Obgene acts as a switch in the co-expression relationship of two genes,Csf1randMilr1. Therefore, the importance of theH2-Obgene as a potential therapeutic target for AD has led us to experimentally validate this relationship using the quantitative real-time PCR technique. In the experimental investigation, we confirmed that a change in the expression levels of theRT1-DObgene (the rat ortholog of murineH2-Ob) can switch the co-expression relationship betweenCsf1randMilr1. Furthermore, since theRT1-DObgene is up-regulated in AD, the mentioned triplets might be related to triggering AD.