Li J, Nelson D, Gibbs R (2014) Cholinergic regulation of aromatase in brain. Neuroscience 2014 Abstracts 640.10. Society for Neuroscience, Washington, DC.
Summary: Our goal is to understand mechanisms by which estrogens can influence brain function and cognition. Estrogens have been shown to influence neuronal plasticity and cognitive performance. Recent studies suggest that, in some cases, local estrogen synthesis can have a greater impact on neuronal survival and plasticity than systemic estrogen administration. Cholinergic projections also have a significant impact on neuronal plasticity in the brain, and recent studies demonstrate critical links between effects of estrogens and effects mediated by cholinergic inputs. In this project we are investigating whether aromatase expression and activity in specific regions of the adult brain are regulated by cholinergic activity. In one experiment, ovariectomized (OVX) rats were treated with the cholinesterase inhibitors donepezil (3 mg/Kg) or galantamine (5 mg/Kg) daily for one week prior to tissue collection. In a second experiment, OVX rats received intraseptal infusions of 192IgG-saporin (SAP) to selectively destroy cholinergic inputs to the hippocampus. Tissues were collected two weeks following the infusions. Different groups of rats were used to evaluate effects on aromatase mRNA and aromatase activity. Effects on aromatase mRNA were evaluated using qRT-PCR. Effects on aromatase activity were evaluated using a novel microsomal assay in which brain tissue microsomes were extracted and activity was measured in vitro by measuring conversion of testosterone to estradiol. Results show an increase in aromatase mRNA in the preoptic area following treatment with galantamine, but no effect in the hippocampus, frontal cortex, or amygdala. Galantamine also produced an increase in aromatase activity in the amygdala, but no significant effect in other brain regions. Donepezil had no significant effects on either aromatase mRNA or activity. Effects of the cholinergic lesions are still being evaluated; however, preliminary results suggest no significant effect on relative levels of aromatase mRNA in the hippocampus. These results indicate that cholinergic manipulations can affect aromatase expression and activity in specific regions of the brain such as the preoptic area and amygdala, with little or no effect in the hippocampus and frontal cortex. This could have important implications for the effects of cholinergic and anticholinergic medications on local estrogen production in the brain.
Related Products: 192-IgG-SAP (Cat. #IT-01)