Effect of chloramine-T on long-term potentiation at synapses between perforant path and dentate gyrus in hippocampus of rats in vivo.
Reactive oxygen species (ROS), including superoxide, are generally considered as neurotoxic molecules whose effects can be alleviated by antioxidant enzymes. However, ROS also are known to be necessary components of the signal transduction cascades underlying normal synaptic plasticity. The oxidant chloramine-T (Ch-T), a specific oxidant to sulphur-containing residues, can oxidize methionine (Met) residues in proteins to alter protein function. To investigate the effect of Ch-T on the induction of hippocampal long-term potentiation (LTP) in dentate gyrus (DG), in vivo electrophysiological recording was employed. It was found that intracerebroventricular (ICV) injection of 0.1 μM Ch-T in 5 μL enhanced hippocampal LTP of rats slightly, whereas, 20 mM Ch-T in 5 μL greatly attenuated LTP. These effects can be reversed by pretreatment with 0.1 mM dithiothretol (DTT), a special thiol reductant. In addition, 0.1 μM Ch-T elevated LTP-induced increase in phosphorylation of Ca²+/calmodulin (CaM)-dependent protein kinase (CaMKII) and neurogranin (Ng), whereas 2 μM and 20 mM Ch-T reduced LTP-induced increase in phosphorylation status of the two key proteins, especially for 20 mM Ch-T. Pretreatment with DTT significantly prevented these effects. Taken together, these findings demonstrated that Ch-T has concentration-dependent effects on the induction of hippocampal LTP in vivo. In brief, low concentration of Ch-T facilitated hippocampal LTP by enhancing LTP-induced increase in p-CaMKII and p-Ng compared to controls, whereas high concentration of Ch-T obviously attenuated LTP accompanied by a decrease in the phosphorylated proteins, and both of these effects can be prevented by DTT. These results indicate that Ch-T modulates hippocampal LTP through regulating phosphorylation status of CaMKII and Ng.
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Jun
J
Yang
Zhuang-Li
ZL
Hu
Bo
B
Jiang
Lan
L
Ni
You
Y
Jin
Jian-Guo
JG
Chen
Fang
F
Wang
D000818:Animals; D002700:Chloramines / Q000494:pharmacology*; D018891:Dentate Gyrus / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D019580:Perforant Pathway / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014105:Tosyl Compounds / Q000494:pharmacology*
D002700:Chloramines; D014105:Tosyl Compounds; C016300:chloramine-T