G-Coupled Protein Estrogen Receptor (Gper) Agonism in the Dorsal Hippocampus Enhances Memory Consolidation in Gonadectomized Male Mice
Mentor 1
Karyn Frick
Start Date
28-4-2023 12:00 AM
Description
Estrogens are hormones involved in many physiological processes beyond reproduction. The most potent estrogen, 17ß-estradiol (E2), regulates learning and memory in both sexes. E2 binds to the classical estrogens receptors (ER), ER-alpha and ER-beta, and the membrane ER G protein-coupled estrogen receptor (GPER). Our laboratory has previously shown that post-training infusion of E2 into the dorsal hippocampus (DH) of ovariectomized female mice improves memory consolidation in the object recognition (OR) and object placement (OP) tasks, effects also observed after infusion of the GPER agonist G-1. In female mice, GPER-induced memory enhancements are mediated by rapid phosphorylation of the JNK, but not ERK, cell signaling pathway. Here, we determined if GPER plays a similar role in memory among gonadectomized male mice. Young male mice underwent bilateral orchiectomy and implantation of bilateral cannulae into the DH. OP and OR were conducted after recovery. In both tasks, mice explored 2 identical objects for 30 sec and then were immediately infused with vehicle or G-1 (4 or 8 ng/h). Either 24 h (OP) and 48 h (OR) later, memory for the location and identity of objects was tested by moving a training object (OP) or substituting a novel object for a training object (OR). After test completion, DH tissue was collected to assess JNK and ERK activation. Immediate post-training DH infusion of G-1 dose-dependently enhanced OR and OP memory consolidation in gonadectomized male mice. Furthermore, the memory-enhancing effects of G-1 were not associated with activation of ERK or JNK signaling 5 or 15 min after infusion, as previously seen in females. Thus, although G-1 enhanced memory in males, as observed previously in female mice, it appears to do so via different cell signaling pathways. Future experiments will untangle this sex difference using different time points for tissue analysis and evaluating different intracellular signaling pathways.
G-Coupled Protein Estrogen Receptor (Gper) Agonism in the Dorsal Hippocampus Enhances Memory Consolidation in Gonadectomized Male Mice
Estrogens are hormones involved in many physiological processes beyond reproduction. The most potent estrogen, 17ß-estradiol (E2), regulates learning and memory in both sexes. E2 binds to the classical estrogens receptors (ER), ER-alpha and ER-beta, and the membrane ER G protein-coupled estrogen receptor (GPER). Our laboratory has previously shown that post-training infusion of E2 into the dorsal hippocampus (DH) of ovariectomized female mice improves memory consolidation in the object recognition (OR) and object placement (OP) tasks, effects also observed after infusion of the GPER agonist G-1. In female mice, GPER-induced memory enhancements are mediated by rapid phosphorylation of the JNK, but not ERK, cell signaling pathway. Here, we determined if GPER plays a similar role in memory among gonadectomized male mice. Young male mice underwent bilateral orchiectomy and implantation of bilateral cannulae into the DH. OP and OR were conducted after recovery. In both tasks, mice explored 2 identical objects for 30 sec and then were immediately infused with vehicle or G-1 (4 or 8 ng/h). Either 24 h (OP) and 48 h (OR) later, memory for the location and identity of objects was tested by moving a training object (OP) or substituting a novel object for a training object (OR). After test completion, DH tissue was collected to assess JNK and ERK activation. Immediate post-training DH infusion of G-1 dose-dependently enhanced OR and OP memory consolidation in gonadectomized male mice. Furthermore, the memory-enhancing effects of G-1 were not associated with activation of ERK or JNK signaling 5 or 15 min after infusion, as previously seen in females. Thus, although G-1 enhanced memory in males, as observed previously in female mice, it appears to do so via different cell signaling pathways. Future experiments will untangle this sex difference using different time points for tissue analysis and evaluating different intracellular signaling pathways.
