Inhibition of local estrogen synthesis in the hippocampus impairs hippocampal memory consolidation in ovariectomized female mice

Abstract

The potent estrogen 17β-Estradiol (E2) plays a critical role in mediating hippocampal function, yet the precise mechanisms through which E2 enhances hippocampal memory remain unclear. In young adult female rodents, the beneficial effects of E2 on memory are generally attributed to ovarian-synthesized E2. However, E2 is also synthesized in the adult brain in numerous species, where it regulates synaptic plasticity and is synthesized in response to experiences such as exposure to females or conspecific song. Although de novo E2 synthesis has been demonstrated in rodent hippocampal cultures, little is known about the functional role of local E2 synthesis in mediating hippocampal memory function. Therefore, the present study examined the role of hippocampal E2 synthesis in hippocampal memory consolidation. Using bilateral dorsal hippocampal infusions of the aromatase inhibitor letrozole, we first found that blockade of dorsal hippocampal E2 synthesis impaired hippocampal memory consolidation. We next found that elevated levels of E2 in dorsal hippocampus observed 30 min after object training were blocked by dorsal hippocampal infusion of letrozole, suggesting that behavioral experience increases acute and local E2 synthesis. Finally, aromatase inhibition did not prevent exogenous E2 from enhancing hippocampal memory consolidation, indicating that hippocampal E2 synthesis is not necessary for exogenous E2 to enhance hippocampal memory. Combined, these data are consistent with the hypothesis that hippocampally-synthesized E2 is necessary for hippocampus-dependent memory consolidation in rodents.

Chronic aromatase inhibition increases ventral hippocampal neurogenesis in middle-aged female mice

“…Finally, in our study we saw no significant effects of letrozole on depressive-like or coping 366 strategies in middle-aged females, but other studies have seen effects of acute letrozole on 367 memory in female mice (Tuscher et al, 2016) and the testing of the effects of chronic letrozole 368 on decision making may be warranted. 369 370 5.…”

Circulating Estradiol Regulates Brain-Derived Estradiol via Actions at GnRH Receptors to Impact Memory in Ovariectomized Rats

“…administration of estradiol to enhance memory consolidation (Tuscher et al, 2016). In addition to differences in tasks and memory processes assessed, there are differences in treatment paradigms that may have contributed to these discrepant results.…”

Neurochemical organization of the ventral striatum’s olfactory tubercle

“…Sex steroid hormones, particularly brain-derived estrogen, play a prominent role supporting synaptic plasticity, transcriptional activity and learning and memory (Saldanha, Remage-Healey, & Schlinger, 2011;Tuscher et al, 2016). The mouse OT is equipped to synthesize estrogen locally because of high expression of aromatase (Stanić et al, 2014), the rate-limiting enzyme that catalyzes androgens into estrogens.…”