The Role of Actin Polymerization in GPER-Mediated Dendritic Spine Morphology in Female Mice
Mentor 1
Karyn Frick
Location
Union Wisconsin Room
Start Date
27-4-2018 1:00 PM
Description
The hippocampus is a medial temporal lobe structure that mediates the formation of many types of memories and deteriorates in aging and Alzheimer’s Disease. Estrogens are important neurotrophic factors, and the potent estrogen 17 beta-estradiol (E2) significantly increases dendritic spine density in the hippocampus. Dendrites of excitatory neurons in the hippocampus are covered in spines, which allow increased neuronal connectivity and therefore facilitate memory consolidation. Hippocampal spine remodeling is dependent on actin cytoskeleton reorganization, and increased actin polymerization is associated with an increase of dendritic spines. Previously, we reported that bilateral dorsal hippocampal (DH) infusion of the G-protein coupled estrogen receptor (GPER), G-1, significantly increased the number of dendritic spines on apical dendrites of CA1 pyramidal neurons in the DH of female mice. We also examined the effects of G-1 on the actin-binding protein cofilin. Cofilin depolymerizes actin filaments, and therefore reduces the formation of dendritic spines. G-1 significantly increased cofilin phosphorylation, which inactivated cofilin. These data suggest GPER activation increases the number of dendritic spines through increasing actin polymerization. To confirm the importance of actin polymerization in GPER-mediated dendritic spine morphogenesis, we examined the effects of latrunculin A, an actin polymerization inhibitor. In our study, ten-week-old female mice were ovariectomized and received a bilateral DH infused of vehicle, G-1, E2, or Latrunculin A. Brains were collected after infusion, and neurons were visualized using Golgi staining. Spines were then counted using NeuroLucida. To examine the cellular mechanisms regulating actin polymerization, the dorsal hippocampus was dissected bilaterally after infusion, and phospho- and total-cofilin were measured using Western blotting. To confirm the necessity of actin rearrangement in GPER-mediated dendritic morphogenesis, we are currently determining the effects of latrunculin A on GPER-mediated hippocampal spine remodeling in female mice. These data support the critical role of actin polymerization in GPER-induced regulation of hippocampal function.
The Role of Actin Polymerization in GPER-Mediated Dendritic Spine Morphology in Female Mice
Union Wisconsin Room
The hippocampus is a medial temporal lobe structure that mediates the formation of many types of memories and deteriorates in aging and Alzheimer’s Disease. Estrogens are important neurotrophic factors, and the potent estrogen 17 beta-estradiol (E2) significantly increases dendritic spine density in the hippocampus. Dendrites of excitatory neurons in the hippocampus are covered in spines, which allow increased neuronal connectivity and therefore facilitate memory consolidation. Hippocampal spine remodeling is dependent on actin cytoskeleton reorganization, and increased actin polymerization is associated with an increase of dendritic spines. Previously, we reported that bilateral dorsal hippocampal (DH) infusion of the G-protein coupled estrogen receptor (GPER), G-1, significantly increased the number of dendritic spines on apical dendrites of CA1 pyramidal neurons in the DH of female mice. We also examined the effects of G-1 on the actin-binding protein cofilin. Cofilin depolymerizes actin filaments, and therefore reduces the formation of dendritic spines. G-1 significantly increased cofilin phosphorylation, which inactivated cofilin. These data suggest GPER activation increases the number of dendritic spines through increasing actin polymerization. To confirm the importance of actin polymerization in GPER-mediated dendritic spine morphogenesis, we examined the effects of latrunculin A, an actin polymerization inhibitor. In our study, ten-week-old female mice were ovariectomized and received a bilateral DH infused of vehicle, G-1, E2, or Latrunculin A. Brains were collected after infusion, and neurons were visualized using Golgi staining. Spines were then counted using NeuroLucida. To examine the cellular mechanisms regulating actin polymerization, the dorsal hippocampus was dissected bilaterally after infusion, and phospho- and total-cofilin were measured using Western blotting. To confirm the necessity of actin rearrangement in GPER-mediated dendritic morphogenesis, we are currently determining the effects of latrunculin A on GPER-mediated hippocampal spine remodeling in female mice. These data support the critical role of actin polymerization in GPER-induced regulation of hippocampal function.
