title: Antagonism of brain insulin-like growth factor-1 receptors blocks estradiol effects on memory and levels of hippocampal synaptic proteins in ovariectomized rats.
abstract: BACKGROUND
  Treatment with estradiol, the primary estrogen produced by the ovaries, enhances hippocampus-dependent spatial memory and increases levels of hippocampal synaptic proteins in ovariectomized rats. Increasing evidence indicates that the ability of estradiol to impact the brain and behavior is dependent upon its interaction with insulin-like growth factor-1 (IGF-1).
  
  
  OBJECTIVE
  The goal of the current experiment was to test the hypothesis that the ability of estradiol to impact hippocampus-dependent memory and levels of hippocampal synaptic proteins is dependent on its interaction with IGF-1.
  
  
  METHODS
  Adult rats were ovariectomized and implanted with estradiol or control capsules and trained on a radial-maze spatial memory task. After training, rats were implanted with intracerebroventricular cannulae attached to osmotic minipumps (flow rate 0.15 μl/h). Half of each hormone treatment group received continuous delivery of JB1 (300 μg/ml), an IGF-1 receptor antagonist, and half received delivery of aCSF vehicle. Rats were tested on trials in the radial-arm maze during which delays were imposed between the fourth and fifth arm choices. Hippocampal levels of synaptic proteins were measured by western blotting.
  
  
  RESULTS
  Estradiol treatment resulted in significantly enhanced memory. JB1 blocked that enhancement. Estradiol treatment resulted in significantly increased hippocampal levels of postsynaptic density protein 95 (PSD-95), spinophilin, and synaptophysin. JB1 blocked the estradiol-induced increase of PSD-95 and spinophilin and attenuated the increase of synaptophysin.
  
  
  CONCLUSIONS
  Results support a role for IGF-1 receptor activity in estradiol-induced enhancement of spatial memory that may be dependent on changes in synapse structure in the hippocampus brought upon by estradiol/IGF-1 interactions.
authors.affiliation: Neuroscience Program, Tulane University, New Orleans, LA, 70118, USA.
authors.forename: Britta S
authors.initials: BS
authors.lastname: Nelson
authors.forename: Rachel C
authors.initials: RC
authors.lastname: Springer
authors.forename: Jill M
authors.initials: JM
authors.lastname: Daniel
mesh_terms: D000818:Animals; D000076122:Disks Large Homolog 4 Protein; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D051528:Guanylate Kinases / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism; D008568:Memory / Q000187:drug effects; D008840:Microfilament Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D065854:Spatial Navigation / Q000187:drug effects; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism; D000099273:Neurabins
chemical_list: D000076122:Disks Large Homolog 4 Protein; D004958:Estradiol; D004965:Estrogen Antagonists; D051528:Guanylate Kinases; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D009842:Oligopeptides; D017526:Receptor, IGF Type 1; D016708:Synaptophysin; D000099273:Neurabins; C501447:Dlg4 protein, mouse; C501449:Dlg4 protein, rat; C411572:H 1356