Basic and clinical research suggests loss of estradiol following menopause may contribute to brain aging and increased risk of age-related cognitive decline and dementia. There is a great need for novel estrogenic compounds that confer positive cognitive effects without risk of side effects. G-1 is a recently developed agonist for the novel transmembrane estrogen receptor (ER) GPR30 [1]. Activation ofthe GPR30 pathway is independent of either of the classical ER a or p pathways, raising the possibility of using G-1 as a novel estrogenic agent that lacks the risks associated with other estrogenic compounds. Previous work in our laboratory has shown that estradiol enhances cognitive performance in rats via effects on basal forebrain cholinergic neurons [13]. We hypothesize that the effects of estradiol on cholinergic function and cognitive performance are mediated, in part, via effects on GPR30. The first goal is to characterize GPR30 expression in the rat forebrain, focusing on co-expression by cholinergic neurons. Preliminary data show extensive co- localization of GPR30 within cholinergic neurons in the septum, digonal band of Broca, and nucleus basils. Because use of the GPR30 antibody on brain tissues is relatively new, GPR30 mRNA expression will also be evaluated using laser capture microscopy and RT-PCR. The second goal is to examine the functional effects of GPR30 activation on the cholinergic neurons. Estradiol has been shown to induce activation of Erk and CREB in brain neurons, including basal forebrain cholinergic neurons. Estradiol also has been shown to increase potassium-stimulated acetylcholine release in the hippocampus, consistent with an effect on basal forebrain cholinergic function. Our studies will evaluate rapid induction of pCREB and pEri
| Gibbs, R B; Nelson, D; Hammond, R (2014) Role of GPR30 in mediating estradiol effects on acetylcholine release in the hippocampus. Horm Behav 66:339-45 |
| Hammond, R; Nelson, D; Kline, E et al. (2012) Chronic treatment with a GPR30 antagonist impairs acquisition of a spatial learning task in young female rats. Horm Behav 62:367-74 |
| Hammond, R; Nelson, D; Gibbs, R B (2011) GPR30 co-localizes with cholinergic neurons in the basal forebrain and enhances potassium-stimulated acetylcholine release in the hippocampus. Psychoneuroendocrinology 36:182-92 |
| Hammond, R; Gibbs, R B (2011) GPR30 is positioned to mediate estrogen effects on basal forebrain cholinergic neurons and cognitive performance. Brain Res 1379:53-60 |
