Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Global COE-21, Suruga-ku, Shizuoka, Japan.
PLoS One. 2011;6(12):e28615. doi: 10.1371/journal.pone.0028615. Epub 2011 Dec 7.
The translocation of synaptic Zn(2+) to the cytosolic compartment has been studied to understand Zn(2+) neurotoxicity in neurological diseases. However, it is unknown whether the moderate increase in Zn(2+) in the cytosolic compartment affects memory processing in the hippocampus. In the present study, the moderate increase in cytosolic Zn(2+) in the hippocampus was induced with clioquinol (CQ), a zinc ionophore. Zn(2+) delivery by Zn-CQ transiently attenuated CA1 long-term potentiation (LTP) in hippocampal slices prepared 2 h after i.p. injection of Zn-CQ into rats, when intracellular Zn(2+) levels was transiently increased in the CA1 pyramidal cell layer, followed by object recognition memory deficit. Object recognition memory was transiently impaired 30 min after injection of ZnCl(2) into the CA1, but not after injection into the dentate gyrus that did not significantly increase intracellular Zn(2+) in the granule cell layer of the dentate gyrus. Object recognition memory deficit may be linked to the preferential increase in Zn(2+) and/or the preferential vulnerability to Zn(2+) in CA1 pyramidal neurons. In the case of the cytosolic increase in endogenous Zn(2+) in the CA1 induced by 100 mM KCl, furthermore, object recognition memory was also transiently impaired, while ameliorated by co-injection of CaEDTA to block the increase in cytosolic Zn(2+). The present study indicates that the transient increase in cytosolic Zn(2+) in CA1 pyramidal neurons reversibly impairs object recognition memory.
已经研究了突触锌离子（Zn2+）向细胞溶质隔室的易位，以了解神经退行性疾病中的 Zn2+神经毒性。然而，尚不清楚细胞溶质隔室中 Zn2+的适度增加是否会影响海马中的记忆处理。在本研究中，使用锌离子载体 clioquinol（CQ）诱导海马细胞溶质中 Zn2+的适度增加。腹腔注射 Zn-CQ 2 小时后，在海马切片中短暂增加细胞内 Zn2+水平，导致 CA1 长时程增强（LTP）短暂减弱，随后出现物体识别记忆缺陷。注射 ZnCl2 到 CA1 后 30 分钟，物体识别记忆短暂受损，但注射到齿状回不会导致细胞内 Zn2+在齿状回颗粒细胞层中显著增加。物体识别记忆缺陷可能与 CA1 锥体神经元中 Zn2+的优先增加和/或对 Zn2+的优先易感性有关。在 100mM KCl 诱导的 CA1 细胞溶质中内源性 Zn2+增加的情况下，物体识别记忆也短暂受损，而通过共同注射 CaEDTA 来阻止细胞溶质 Zn2+的增加则可改善这种情况。本研究表明，CA1 锥体神经元中细胞溶质 Zn2+的短暂增加可可逆地损害物体识别记忆。
