Streptozotocin Inhibits Electrophysiological Determinants of Excitatory and Inhibitory Synaptic Transmission in CA1 Pyramidal Neurons of Rat Hippocampal Slices: Reduction of These Effects by Edaravone

Autor: Yi Xu, Ting Ju, Jinghan Lin, Tingting Zhao, Meimei Yang, Lina Sun, Yuru Li, Xiaoran Wang, Shanshan Zhou, Lifeng Xiao, Liming Zhang, Tingjiao Liu, Li Jiang
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
endocrine system diseases
Physiology
Postsynaptic Current
Neural facilitation
AMPA receptor
Pharmacology
Neurotransmission
Inhibitory postsynaptic potential
Electric Capacitance
Synaptic Transmission
lcsh:Physiology
Streptozocin
Membrane Potentials
lcsh:Biochemistry
03 medical and health sciences
Glutamatergic
0302 clinical medicine
Evoked excitatory postsynaptic currents (eEPSCs)
Edaravone
Animals
lcsh:QD415-436
Rats
Wistar
CA1 Region
Hippocampal
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
lcsh:QP1-981
Streptozotocin
Chemistry
Pyramidal Cells
Evoked inhibitory postsynaptic currents (eIPSCs)
Excitatory Postsynaptic Potentials
Paired pulse ratio (PPR)
Free radical scavenger
030104 developmental biology
Anesthesia
Excitatory postsynaptic potential
Female
Slice patch clamp
030217 neurology & neurosurgery
Antipyrine
Zdroj: Cellular Physiology and Biochemistry, Vol 40, Iss 6, Pp 1274-1288 (2016)
ISSN: 1421-9778
Popis: 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. Conclusion: 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.
Databáze: OpenAIRE
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