Abstract Details

Title G Protein-Coupled Estrogen Receptor (GPER) Activation in the Dorsal Hippocampus of Gonadectomized Male Mice Regulates Memory Consolidation via Distinct Intracellular Pathways Than in Female Mice

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P5 - Poster Session 5 (8:00 AM-9:00 AM)

Poster/Presentation
Number 3-007

Objective In the present work we evaluated at which extent the pharmacological activation of the G Protein-Coupled Estrogen Receptor (GPER) modulates memory consolidation in gonadectomized male mice and the intracellular pathways mediating these effects.

Background Studies have demonstrated the beneficial effects of 17-beta-estradiol (E2) on memory consolidation. The rapid effects of E2 are attributed to its binding to different estrogen receptors (ER), ERα, ERβ, and GPER. Post-training DH infusion of the GPER agonist G-1 enhanced memory consolidation in ovariectomized (OVX) female mice

Design/Methods Male gondectomized mice underwent behavioral tasks: object placement (OP) and object recognition (OR), post-training, animals were infused with G-1 or G-15 (GPER antagonist). For G-1, memory consolidation was evaluated 48 h later in OR and 24 h later in OP. For G-15, memory was tested 24 and 4 hours later in OR and OP, respectively. After the final behavioral test, mice were infused with G-1 and the DH was collected 5, 15, or 30 min later to determine levels of phosphorylated JNK, cofilin, ERK, PI3K, Akt, and CREB via Western blotting.

Results Immediate post-training bilateral DH infusion of G-1 enhanced memory consolidation in object placement and object recognition tasks, as previously demonstrated in OVX mice. As in females, treatment of males with G-15 impaired memory consolidation in both tasks. Interestingly, GPER activation in the DH of male mice did not increase the levels of phospho-JNK or phosphor-cofilin as previously observed in female OVX mice, suggesting involvement of different signaling proteins in the effects of GPER in males. Levels of CREB were elevated in the DH 30 minutes following G-1 infusion, indicating that GPER in males activates an as yet unknown mechanism that triggers CREB-mediated gene transcription.

Conclusions There are sex differences mediating the molecular mechanisms of GPER activation, and it might represent a promising therapeutic target for the treatment of memory-related disorders.

Authors/Disclosures
Gustavo Dalto Barroso Machado, MD, MS PRESENTER	Dr. Barroso Machado has nothing to disclose.
Alexis Schnitzler	Ms. Schnitzler has nothing to disclose.
Aaron Fleischer	Mr. Fleischer has nothing to disclose.
Sarah Beamish, MS	Ms. Beamish has nothing to disclose.
Karyn Frick, PhD	Dr. Frick has received personal compensation for serving as an employee of Estrigenix Therapeutics, Inc.. Dr. Frick has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for eNeuro. Dr. Frick has stock in Estrigenix Therapeutics, Inc.. The institution of Dr. Frick has received research support from National Institutes of Health. The institution of Dr. Frick has received research support from Alzheimer's Association. The institution of Dr. Frick has received research support from UWM Research Foundation. Dr. Frick has received intellectual property interests from a discovery or technology relating to health care.

��ɫ��

��ɫ��