Global
ischemia in humans or induced experimentally in animals causes selective and delayed neuronal death in pyramidal neurons of the hippocampal CA1. The ovarian
hormone estradiol administered before or immediately after insult affords histological protection in experimental models of focal and global
ischemia and ameliorates the cognitive deficits associated with ischemic cell death. However, the impact of
estradiol on the functional integrity of Schaffer collateral to CA1 (Sch-CA1) pyramidal cell synapses following global
ischemia is not clear. Here we show that long term
estradiol treatment initiated 14 days prior to global
ischemia in ovariectomized female rats acts via the
IGF-1 receptor to protect the functional integrity of CA1 neurons. Global
ischemia impairs basal synaptic transmission, assessed by the input/output relation at Sch-CA1 synapses, and
NMDA receptor (NMDAR)-dependent long term potentiation (LTP), assessed at 3 days after surgery. Presynaptic function, assessed by fiber volley and paired pulse facilitation, is unchanged. To our knowledge, our results are the first to demonstrate that
estradiol at near physiological concentrations enhances basal excitatory synaptic transmission and ameliorates deficits in LTP at synapses onto CA1 neurons in a clinically-relevant model of global
ischemia.
Estradiol-induced rescue of LTP requires the
IGF-1 receptor, but not the classical
estrogen receptors (ER)-α or β. These findings support a model whereby
estradiol acts via the
IGF-1 receptor to maintain the functional integrity of hippocampal CA1 synapses in the face of global
ischemia. This article is part of a Special Issue entitled SI: Brain and Memory.