SRC-1 Knockout Exerts No Effect on Amyloid ß Deposition in APP/PS1 Mice.

ABSTRACT

Steroid receptor coactivator 1 (SRC-1) is the key coactivator because of its transcriptional activity. Previous studies have shown that SRC-1 is abundant in the hippocampus and has been implicated in cognition. SRC-1 is also related to some major risk factors for Alzheimer's disease (AD), such as a decline in estrogen and aging, however, whether SRC-1 is involved in the pathogenesis of AD remains unclear. In this study, we established SRC-1 knockout in AD mice by cross breeding SRC-1-/- mutant mice with APP/PS1 transgenic mice, and investigated the expression of some synaptic proteins, the amyloid ß (Aß) deposition, and activation of astrocytes and microglia in the hippocampus of APP/PS1×SRC-1-/- mice. The results showed that SRC-1 knockout neither affects the Aß plaque and activation of glia, nor changes the expression of synaptic proteins in AD model mice. The above results suggest that the complete deletion of SRC-1 in the embryo exerts no effect on the pathogenesis of APP/PS1 mice. Nevertheless, this study could not eliminate the possible role of SRC-1 in the development of AD due to the lack of observation of other events in AD such as tau hyperphosphorylation and the limitation of the animal model employed.