title: Estradiol pretreatment ameliorates impaired synaptic plasticity at synapses of insulted CA1 neurons after transient global ischemia.
abstract: 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.
authors.affiliation: Dominick P. Purpura Department of Neuroscience, Rose F. Kennedy Center for Research in Mental Retardation and Developmental Disabilities, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Koichi
authors.initials: K
authors.lastname: Takeuchi
authors.affiliation: Dominick P. Purpura Department of Neuroscience, Rose F. Kennedy Center for Research in Mental Retardation and Developmental Disabilities, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Yupeng
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Dominick P. Purpura Department of Neuroscience, Rose F. Kennedy Center for Research in Mental Retardation and Developmental Disabilities, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Takayasu
authors.affiliation: Dominick P. Purpura Department of Neuroscience, Rose F. Kennedy Center for Research in Mental Retardation and Developmental Disabilities, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Gertner
authors.affiliation: Dominick P. Purpura Department of Neuroscience, Rose F. Kennedy Center for Research in Mental Retardation and Developmental Disabilities, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Jee-Yeon
authors.initials: JY
authors.lastname: Hwang
authors.affiliation: Dominick P. Purpura Department of Neuroscience, Rose F. Kennedy Center for Research in Mental Retardation and Developmental Disabilities, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Aromolaran
authors.affiliation: Dominick P. Purpura Department of Neuroscience, Rose F. Kennedy Center for Research in Mental Retardation and Developmental Disabilities, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Michael V L
authors.initials: MV
authors.lastname: Bennett
authors.affiliation: Dominick P. Purpura Department of Neuroscience, Rose F. Kennedy Center for Research in Mental Retardation and Developmental Disabilities, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA. Electronic address: suzanne.zukin@einstein.yu.edu.
authors.forename: R Suzanne
authors.initials: RS
authors.lastname: Zukin
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000503:physiopathology*; D004958:Estradiol / Q000008:administration & dosage*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D005260:Female; D002546:Ischemic Attack, Transient / Q000503:physiopathology* / Q000517:prevention & control; D017774:Long-Term Potentiation / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D009842:Oligopeptides / Q000494:pharmacology; D010052:Ovariectomy; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology
chemical_list: D018696:Neuroprotective Agents; D009842:Oligopeptides; C411572:H 1356; D004958:Estradiol; D017526:Receptor, IGF Type 1
keywords: Estradiol; Global ischemia; IGF-1 receptor; Long term potentiation; Synaptic plasticity