Premium
[P2–172]: APOE AND ALLOPREGNANOLONE: EVALUATING DIFFERENCES IN RESPONSE TO TREATMENT BY GENDER AND GENOTYPE
Author(s) -
Desai Maunil K.,
Irwin Ronald W.,
Prajapati Mayur,
Diaz Brinton Roberta
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.06.823
Subject(s) - apolipoprotein e , medicine , allopregnanolone , population , disease , physiology , genotype , allele , endocrinology , neuroactive steroid , biology , genetics , receptor , environmental health , gabaa receptor , gene
neurofibrillary tangles and is expressed by degenerating AD neurons (Caricasole et al, 2004). Despite the apparent role for Wnt/b-catenin signaling in AD, the role of E2 in mediating this signaling pathway is less well characterized. The goal of the present study was to determine the extent to which Wnt/b-catenin signaling regulates E2induced memory enhancement, in the hopes of providing putative new targets for drug development to alleviate AD. Methods: Female C57/BL6 mice were ovariectomized and implanted with chronic indwelling cannulae in the dorsal hippocampus (bilateral) and dorsal third ventricle (unilateral). Mice received hippocampal infusions of vehicle or Dkk-1 and intraventricular infusion of vehicle or E2 immediately after objectmemory training.Memorywas tested 24-48 h later. Following completion of testing, micewere re-infused, and hippocampal tissue collected for Western blotting and qPCR measurement of E2and Dkk-1 effects on Wnt-related proteins and mRNA targets. Results: E2 enhanced memory as expected, whereas blockade of Wnt/ b-catenin signaling prevented E2-induced memory enhancement. Furthermore, Western blotting and qPCR data indicate that E2and Dkk-1 differentially modulate Wnt/b-catenin signaling. Conclusions: These data suggest thatWnt/b-catenin signaling, a pathway previously implicated in AD-related neuropathology, is essential for the memory enhancing effects of E2. These findings implicate Wnt/b-catenin signaling as a potential target for the development of novel therapeutic targets for the treatment of AD in women.