Impairment of recognition memory and hippocampal long-term potentiation after acute exposure to clioquinol.
Clioquinol (CQ) was associated with cases of transient global amnesia and with the neurodegenerative syndrome subacute myelo-optico-neuropathy (SMON) in humans. However, CQ forms lipophilic chelates with cations and has the potential as a scientific and clinical tool used for selective modulation of histochemically reactive zinc pools. The relationship among transient lack of synaptic zinc release, hippocampal long-term potentiation (LTP) induction and cognitive memory is poorly understood. To evaluate the role of synaptic zinc release, in the present study, hippocampal LTP induction and cognitive behavior were examined in young rats after i.p. injection of CQ (30 mg/kg). Intracellular zinc detected by Timm's stain and extracellular (synaptic cleft) zinc detected by ZnAF-2 were significantly decreased in the hippocampus 6 h after CQ injection. The molecular layer of the dentate gyrus, in which perforant path-granule cell synapses exist, was most responsive to CQ injection. Dentate gyrus LTP was induced similarly to the control 2 h after CQ injection, while significantly attenuated 6-24 h after CQ injection. In the training trial of the object recognition memory 2 h after CQ injection, there was no significant difference in learning behavior between the control and CQ-treated rats. In the test trial, CQ-treated rats showed normal recognition memory 1 h after the training, whereas recognition memory deficit 24 h after the training unlike the control rats. These results indicate that acute exposure to CQ impairs long-term (24 h) memory in the hippocampus of young rats. The CQ-mediated attenuation of dentate gyrus LTP, which may be associated with the transient lack of zinc release from zincergic neurons, seems to be involved in the impairment of the long-term memory.
Takeda
A
A
Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Global COE-21, 52- 1 Yada, Surugaku, Shizuoka 422-8526, Japan. takedaa@u-shizuoka-ken.ac.jp
Takada
S
S
Ando
M
M
Itagaki
K
K
Tamano
H
H
Suzuki
M
M
Iwaki
H
H
Oku
N
N
D000818:Animals; D007464:Clioquinol / Q000633:toxicity*; D003071:Cognition / Q000187:drug effects; D018891:Dentate Gyrus / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D008568:Memory / Q000187:drug effects*; D051381:Rats; D021641:Recognition, Psychology / Q000187:drug effects*; D015032:Zinc / Q000502:physiology
D007464:Clioquinol; D015032:Zinc