Jun Ming Wang
University of Mississippi Medical Center, USA
Title: Alternative RNA splicing of estrogen receptor β and neurogenesis/mood/cognitive behavior in Post-menopause
Biography
Biography: Jun Ming Wang
Abstract
Dementia and depression disproportionately affect women in both prevalence and severity. Particularly related to deficiency of ovarian hormones which impairs the homeostasis of the brain microenvironment, reduces neurogenesis, and leads to neurodegeneration. Accumulated data suggest that estradiol-17β (E2), the primary ovarian hormone, promotes hippocampal neural progenitor cell (NPC) proliferation in vitro, in vivo, and after brain injury. Our earlier work indicated that activation of estrogen receptor (ER) β by the ERβ-specific ligand, diarylpropionitrile, led to an increase in phosphorylated extracellular signal-regulated kinase in human neural progenitor cells and increased these cell proliferation. Our resent work suggested that ovariectomy (OVX) increased alternative splicing of ER β and the ERβ splice variants might mediate the differential effects of estrogen therapy (ET) in early and late post-menopause. To further understand the mechanism, we used a customized RT2 Profiler PCR Array to examine expressions of RNA splicing factors in brain of female rats treated with E2, ERβ or ERα specific agonists, or vehicle 6-day (early) or 180-day (late) after OVX. Early ET reversed OVX-increased (SFRS7 and SFRS16) or -decreased (ZRSR2 and CTNNB1) mRNA levels of splicing factors and ERβ splicing changes in brains and leukocytes, and improved mood/cognitive performances. While only DPN (an ERβ specific agonist), but not E2 (an ERα and ERβ agonist) nor PPT (an ERα specific agonist), achieved similar results in late treatment. These data suggests ERβ plays an important role in ET and ET efficiency may be indicated the expression of ERβ splice variant in circulation.