Streptozotocin inhibits synaptic transmission and edaravone attenuates streptozotocin-induced electrophysiological changes in CA1 pyramidal neurons of rat hippocampal slices

Neurotoxicology. 2016 Dec:57:75-86. doi: 10.1016/j.neuro.2016.09.005. Epub 2016 Sep 13.

Abstract

The purpose of this study was to investigate the acute and chronic effects of streptozotocin (STZ) upon synaptic transmission and the effects of edaravone (EDA, a free radical scavenger) on STZ-induced electrophysiological changes in CA1 pyramidal neurons of rat hippocampal slices. To accomplish this goal, spontaneous excitatory postsynaptic current (sEPSC), miniature excitatory postsynaptic current (mEPSC), spontaneous inhibitory postsynaptic current (sIPSC) and miniature inhibitory postsynaptic current (mIPSC) were recorded within hippocampal slices using whole-cell patch clamp techniques. The results showed that the amplitudes and frequencies of sEPSC, mEPSC, sIPSC and mIPSC were inhibited by 1000μM STZ, while treatment of EDA (1000μM) attenuated these STZ-induced changes. The degree of these neurotoxic effects of STZ and effects of EDA increased as a function of drug duration as assessed at 2, 4 or 8h of exposure. Taken together, our results demonstrate that STZ induces neurotoxicity within these hippocampal slices through its capacity to alter synaptic transmission and these STZ-induced alterations in electrophysiological responses are attenuated by EDA.

Keywords: EPSC; Edaravone; IPSC; Pyramidal neuron; Slice patch clamp; Streptozotocin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Animals
  • Animals, Newborn
  • Antibiotics, Antineoplastic / pharmacology*
  • CA1 Region, Hippocampal / cytology*
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Antagonists / pharmacology
  • Female
  • In Vitro Techniques
  • Male
  • Patch-Clamp Techniques
  • Pyramidal Cells / drug effects*
  • Rats
  • Rats, Wistar
  • Streptozocin / pharmacology*
  • Synaptic Transmission / drug effects*
  • Time Factors
  • Valine / analogs & derivatives
  • Valine / pharmacology

Substances

  • Antibiotics, Antineoplastic
  • Excitatory Amino Acid Antagonists
  • Streptozocin
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • 2-amino-5-phosphopentanoic acid
  • Valine