Clioquinol and vitamin B12 (cobalamin) synergistically rescue the lead-induced impairments of synaptic plasticity in hippocampal dentate gyrus area of the anesthetized rats in vivo.
Lead (Pb(2+)) exposure in development induces impairments of synaptic plasticity in the hippocampal dentate gyrus (DG) area of the anesthetized rats in vivo. The common chelating agents have many adverse effects and are incapable of alleviating lead-induced neurotoxicity. Recently, CQ, clioquinol (5-chloro-7-iodo-8-hydroxy-quinoline), which is a transition metal ion chelator and/or ionophore with low affinity for metal ions, has yielded some promising results in animal models and clinical trials related to dysfunctions of metal ions. In addition, CQ-associated side effects are believed to be overcome with vitamin B12 (VB12) supplementation. To determine whether CQ treatment could rescue impairments of synaptic plasticity induced by chronic Pb(2+) exposure, we investigated the input/output functions (I/Os), paired-pulse reactions (PPRs) and long-term potentiation (LTP) of different treatment groups in hippocampal DG area of the anesthetized rat in vivo by recording field potentials and measured hippocampal Pb(2+) concentrations of different treatment groups by PlasmaQuad 3 inductive coupled plasma mass spectroscopy. The results show: CQ alone does not rescue the lead-induced impairments of synaptic plasticity in hippocampal DG area of the anesthetized rats in vivo; VB12 alone partly rescues the lead-induced impairments of LTP; however the co-administration of CQ and VB12 totally rescues these impairments of synaptic plasticity and moreover, the effects of CQ and VB12 co-administration are specific to the lead-exposed animals.
Chen
W-H
WH
School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, PR China. stancak@lf3.cuni.cz
Wang
M
M
Yu
S-S
SS
Su
L
L
Zhu
D-M
DM
She
J-Q
JQ
Cao
X-J
XJ
Ruan
D-Y
DY
D000704:Analysis of Variance; D000758:Anesthesia; D000818:Animals; D007464:Clioquinol / Q000627:therapeutic use*; D018891:Dentate Gyrus / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D007855:Lead Poisoning / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000187:drug effects*; D014805:Vitamin B 12 / Q000627:therapeutic use*; D014803:Vitamin B Complex / Q000627:therapeutic use*
D014803:Vitamin B Complex; D007464:Clioquinol; D014805:Vitamin B 12