Rapid Actions of Estradiol upon Hippocampal Neuronal Function
Research Scientist II, Medical College of Wisconsin
Undergraduate Institution and Major/Degree:
- Miami University of Ohio, BS, Zoology, 2000
- Miami University of Ohio, BA, Psychology, 2000
Paul Mermelstein, Ph.D.
In addition to mediating sexual maturation and reproduction through stimulation of classical intracellular receptors that bind DNA and regulate gene expression, estradiol is also thought to influence various brain functions by acting upon receptors localized to the neuronal membrane surface. Many intracellular signaling pathways and modulatory proteins are affected by estradiol via this unconventional route, including regulation of the transcription factor cAMP response element-binding protein (CREB).
However, the mechanisms by which estradiol acts at the membrane surface are poorly understood. Because both estradiol and CREB have been implicated in regulating learning and memory, my dissertation research is aimed to characterize the effects of estradiol upon this transcription factor in cultured rat hippocampal neurons.
The three main objectives of this thesis proposal are:
1. To characterize the effects of estradiol upon CREB phosphorylation
2. To better define the signaling pathway by which estradiol regulates CREB
3. To determine the mechanism by which estradiol mediates these responses
To date, we have found that estradiol both increases and decreases CREB activation, with directional changes dependent upon the absence or presence of additional neuronal stimuli. Furthermore, estradiol influences CREB through activation of two distinct signaling pathways, triggered by stimulation of group I and II metabotropic glutamate receptors. For the remainder of this project, we will focus on determining the mechanism by which estradiol activates metabotropic glutamate receptors.
- Kevin Wickman
- Paulo Kofuji
- Paul Mermelstein
Courses Taken Beyond the Core Courses:
- BIOC 4331 Structure/Catalysis/Metabolism
- GCD 8213 Topics in Molecular Biology
- BIOC 4332 Signal Trans/Gene Expression
Conferences Attended and Presentations:
- Society for Neuroscience annual meeting - Fall 2001, 2002, 2003
- Spring Brain - March 2004
- Steroid Hormones and Brain Function - March 2005
- Bill Engeland - Chair
- Lance Zirpel
- Marty Wessendorf
- Paul Mermelstein - Advisor
- Tonn Eisinger KR, Larson EB, Boulware MI, Thomas MJ, Mermelstein PG. Membrane estrogen receptor signaling impacts the reward circuitry of the female brain to influence motivated behaviors. Steroids. 2017 Nov 28. pii: S0039-128X(17)30224-6.
- Meitzen J, Luoma JI, Boulware MI, Hedges VL, Peterson BM, Tuomela K, Britson KA, Mermelstein PG. Palmitoylation of estrogen receptors is essential for neuronal membrane signaling. Endocrinology. 2013;154(11):4293-304.
- Zhao Z, Fan L, Fortress AM, Boulware MI, Frick KM. Hippocampal histone acetylation regulates object recognition and the estradiol-induced enhancement of object recognition. J Neurosci. 2012;32:2344-2351.
- Grove-Strawser D, Boulware MI, Mermelstein PG. Membrane estrogen receptors activate the metabotropic glutamate receptors mGluR5 and mGluR3 to bidirectionally regulate CREB phosphorylation in female rat striatal neurons. Neuroscience. 2010;170:1045-1055.
- Boulware MI, Mermelstein PG. Membrane estrogen receptors activate metabotropic glutamate receptors to influence nervous system physiology. Steroids. 2008;74:608-613.
- Luoma JI, Boulware MI, Mermelstein PG. Caveolin proteins and estrogen signaling in the brain. Mol Cell Endocrinol. 2008;290:8-13.
- Boulware MI, Kordasiewicz H, Mermelstein PG. Caveolin proteins are essential for distinct effects of membrane estrogen receptors. J Neurosci. 2007;27:9941-50.
- Dewing P, Boulware MI, Sinchak K, Christensen A, Mermelstein PG, Micevych PE. Membrane ERα interacts with mGluR1a to modulate female sexual receptivity. J Neurosci.2007; 27: 9294-300.
- Boulware MI, Mermelstein PG. The influence of estradiol on nervous system function. Drug News Perspect. 2005;18:631-637.
- Boulware MI, Weick JP, Becklund BR, Kuo SP, Groth RD, Mermelstein PG. Estradiol activates group I and II metabotropic glutamate receptor signaling, leading to opposing influences on cAMP response element-binding protein. J. Neurosci. 2005;25:5066-5078.
- Bradley KC, Boulware MB, Jiang H, Doerge R, Meisel RL, Mermelstein PG. Changes in gene expression within the nucleus accumbens and striatum following sexual experience. Genes Brain Behav. 2005;4:31-44.
- Society for Neuroscience
- Moore, South Carolina