Effect of Ovariectomy, Estrogen and Cholinergic Input on Aromatase in Different Brain Regions

Our goal is to understand mechanisms by which estrogen can influence brain function and cognition. Cholinergic projections have a significant impact on neuronal plasticity and cognition in the brain. Estrogen has been shown to influence neuronal plasticity as well, and this effect can be mediated by the cholinergic system. Recent studies suggest that local estrogen synthesis, which is regulated by many neurotransmitters and hormones, can have a greater impact on neuronal survival and plasticity than systemic estrogen administration. One possible way for the cholinergic system to influence estrogen functions in the brain is through the regulation of local estrogen production. In this project, we hypothesize that cholinergic inputs can regulate aromatase (ARO) expression and activity in specific regions of the adult brain, leading to neuroprotection and increase synaptic plasticity. To test this hypothesis, a RT-PCR assay was developed to quantify ARO mRNA; and a microsomal incubation method was established to test ARO activity. First we tested the effects of ovariectomy and estrogen or G1 (a GPR30 agonist) treatments on ARO mRNA and activity in different brain regions. This was important because subsequent experiments would be conducted using ovariectomized rats. The second goal was to test the effects of removing cholinergic inputs on ARO in the hippocampus. Selective cholinergic lesions were performed, yet there was no effect of lesions on either ARO mRNA or activity in the hippocampus. The third goal was to test the effect of cholinesterase inhibitor (ChEI) treatments on ARO in different brain regions. Two ChEIs--Donepezil and Galantamine--which are used in treating Alzheimer’s dementia were used. ChEI treatments changed neither ARO mRNA level nor activity in the hippocampus or frontal cortex. Hence, our results suggest that cholinergic system do not regulate ARO in these regions of the brain. This suggests that the regulation of local estrogen production is not a mechanism by which cholinergic inputs regulate neural plasticity in these regions. However, ChEIs did increase ARO activity in the amygdala, which is a region that is important for anxiety and emotion. Hence it is possible that cholinergic inputs may regulate emotional function in the amygdala through aromatase