In vivo measurement of presynaptic Zn2+ release during forebrain ischemia in rats.
Previous studies have suggested that during forebrain ischemia, considerable Zn2+ is released from synaptic vesicles of gultamatergic neuronal terminals and accumulates in hippocampal CA1 pyramidal neurons, leading to delayed neuronal death. However, since a time lag exists between the accumulation of Zn2+ and the occurrence of ischemia and there are conflicting reports about the amount of Zn2+ released, the level of released Zn2+ during ischemia in vivo is still unclear. In this study, we investigated the temporal change of extracellular Zn2+ in the hippocampal CA1 area using microdialysis and the accumulation of Zn2+ in hippocampal CA1 neurons with TSQ staining in rats with a transient forebrain ischemia. The level of extracellular Zn2+ in the CA1 area increased transiently reaching a peak 15 min after occlusion, then decreased with time, returning to the basal level 15 min after reperfusion. In addition, at this peak, the level of extracellular Zn2+ was about twice the basal level. Assessment of the intracellular Zn2+ in hippocampal neurons with TSQ revealed that Zn2+ accumulate at 24 h, but not 0 and 6 h after ischemia. These results suggest that, although the synaptic vesicular Zn2+ is released into the synaptic cleft during ischemia in vivo, the amount of released Zn2+ might not be so excessive, and it does not accumulate in hippocampal CA1 pyramidal neurons immediately after ischemia.
Kitamura
Youji
Y
Graduate School of Medicine and Dentistry and Pharmaceutical Sciences, Okayama University, Tsushimanaka, Japan.
Iida
Yasuhiko
Y
Abe
Jun
J
Mifune
Masaki
M
Kasuya
Fumiyo
F
Ohta
Masayuki
M
Igarashi
Kazuo
K
Saito
Yutaka
Y
Saji
Hideo
H
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D005456:Fluorescent Dyes; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D016548:Prosencephalon / Q000098:blood supply*; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism*
D005456:Fluorescent Dyes; D017661:Receptors, Presynaptic; D018698:Glutamic Acid; D015032:Zinc