Influence Of Estradiol On The Ability Of Igf-i To Impact Hippocampal-dependent Memory And Hippocampal Synaptic Proteins
The ability of insulin-like growth factor-I (IGF-I) to impact the hippocampus and associated behaviors may vary depending upon estrogenic status. Previous work from our lab demonstrated that chronic antagonism of brain IGF-I receptors (IGF-IR) resulted in increased levels of hippocampal synaptic proteins in control-treated ovariectomized (OVX) rats. In contrast, antagonism of brain IGF-IR decreased levels of synaptic proteins in estradiol-treated OVX rats. The goal of the current experiment was to test the hypothesis that effects of chronic agonism of IGF-IR, via peripheral treatment with IGF-I, on hippocampal-dependent memory would also vary with estrogenic status. Furthermore, we assessed the influence of estrogenic status on the ability of IGF-I to impact levels of hippocampal synaptic proteins. OVX rats received chronic peripheral treatment with estradiol or cholesterol control via silastic implants, as well as IGF-I or vehicle via osmotic minipumps. One week after surgeries, place learning and memory on the Morris water maze was assessed via eight place-training trials on the first day and four place-training trials on the second day of testing. Place learning and memory was measured using mean swim path length. Following place training, a probe trial was conducted to assess memory for the location of the hidden platform. Memory on the probe trial was measured via percent time in the target quadrant. Animals were euthanized 24 hours following behavioral testing, and hippocampi were processed for western blotting to determine levels of hippocampal synaptic proteins PSD-95, spinophilin, and synaptophysin. Results revealed no effects of treatment on behavioral measures or on levels of hippocampal synaptic proteins. These data indicate that chronic peripheral administration of IGF-I does not affect hippocampal-dependent memory in a Morris water maze task and does not impact hippocampal synaptic protein levels in the presence or absence of peripheral estradiol.