title: Streptozotocin Inhibits Electrophysiological Determinants of Excitatory and Inhibitory Synaptic Transmission in CA1 Pyramidal Neurons of Rat Hippocampal Slices: Reduction of These Effects by Edaravone.
abstract: BACKGROUND
  Streptozotocin (STZ) has served as an agent to generate an Alzheimer's disease (AD) model in rats, while edaravone (EDA), a novel free radical scavenger, has recently emerged as an effective treatment for use in vivo and vitro AD models. However, to date, these beneficial effects of EDA have only been clearly demonstrated within STZ-induced animal models of AD and in cell models of AD. A better understanding of the mechanisms of EDA may provide the opportunity for their clinical application in the treatment of AD. Therefore, the purpose of this study was to investigate the underlying mechanisms of STZ and EDA as assessed upon electrophysiological alterations in CA1 pyramidal neurons of rat hippocampal slices.
  
  
  METHODS
  Through measures of evoked excitatory postsynaptic currents (eEPSCs), AMPAR-mediated eEPSCs (eEPSCsAMPA), evoked inhibitory postsynaptic currents (eIPSCs), evoked excitatory postsynaptic current paired pulse ratio (eEPSC PPR) and evoked inhibitory postsynaptic current paired pulse ratio (eIPSC PPR), it was possible to investigate mechanisms as related to the neurotoxicity of STZ and reductions in these effects by EDA.
  
  
  RESULTS
  Our results showed that STZ (1000 µM) significantly inhibited peak amplitudes of eEPSCs, eEPSCsAMPA and eIPSCs, while EDA (1000 µM) attenuated these STZ-induced changes at holding potentials ranging from -60mV to +40 mV for EPSCs and -60mV to +20 mV for IPSCs. Our work also indicated that mean eEPSC PPR were substantially altered by STZ, effects which were partially restored by EDA. In contrast, no significant effects upon eIPSC PPR were obtained in response to STZ and EDA.
  
  
  CONCLUSIONS
  Our data suggest that STZ inhibits glutamatergic transmission involving pre-synaptic mechanisms and AMPAR, and that STZ inhibits GABAergic transmission by post-synaptic mechanisms within CA1 pyramidal neurons. These effects are attenuated by EDA.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: Ju
authors.forename: Yuru
authors.initials: Y
authors.lastname: Li
authors.forename: Xiaoran
authors.initials: X
authors.lastname: Wang
authors.forename: Lifeng
authors.initials: L
authors.lastname: Xiao
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhou
authors.forename: Meimei
authors.initials: M
authors.lastname: Yang
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhao
authors.forename: Lina
authors.initials: L
authors.lastname: Sun
authors.forename: Tingjiao
authors.initials: T
authors.lastname: Liu
authors.forename: Jinghan
authors.initials: J
authors.lastname: Lin
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.forename: Liming
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D056547:CA1 Region, Hippocampal / Q000166:cytology*; D000077553:Edaravone; D025802:Electric Capacitance; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D017208:Rats, Wistar; D013311:Streptozocin / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
chemical_list: D013311:Streptozocin; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D000077553:Edaravone; D000983:Antipyrine