Medroxyprogesterone acetate exacerbates glutamate excitotoxicity

摘要: We previously demonstrated that progesterone functions as a neuroprotective agent whereas medroxyprogesterone acetate (MPA; Provera) does not. Moreover, MPA antagonized the and neurotrophic outcomes induced by 17beta-estradiol (E2). Towards developing effective hormone therapies for protection against neurodegeneration, we sought to determine whether formulation, chemical features or prevention versus treatment mode of exposure affected outcome in survival primary hippocampal neurons. Results these analyses indicated both crystalline pharmaceutical formulation (Depo-Provera) lacked efficacy, indicating effects were not dependent upon formulation. Likewise, paradigms equally ineffective at promoting neuronal survival, timing administration was factor. Further, detrimental due presence group, survival. pretreatment exacerbated neuron death glutamate excitotoxicity 40% increase determined direct live/dead cell count commensurate number positive cells terminal deoxynucleotidyl transferase-mediated nick end-labeling. Collectively results predict progestin therapy will affect vulnerability central nervous system degenerative insults.