Involvement of glucocorticoid-mediated Zn²⁺ signaling in attenuation of hippocampal CA1 LTP by acute stress

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• 作者：Atsushi Takeda ; ^{takedaa@u-shizuoka-ken.ac.jp} ; Miki Suzuki ; Haruna Tamano ; Shunsuke Takada ; Kazuki Ide ; Naoto Oku
• 关键词：Stress ; Glucocorticoid ; Glutamatergic neuron ; Hippocampus ; LTP ; Zn2+ signaling
• 刊名：Neurochemistry International
• 出版年：2012
• 期刊代码：120_01970186
• 类别：bio
• 出版时间：March, 2012
• 卷：60
• 期：4
• 页码：394-399
• 文件大小：1246 K

摘要

Glucocorticoid-glutamatergic interactions have been proposed as a potential model to explain stress-mediated impairment of cognition. However, it is unknown whether glucocorticoid-zincergic interactions are involved in this impairment. Histochemically reactive zinc (Zn²⁺) is co-released with glutamate from zincergic neurons. In the present study, involvement of synaptic Zn²⁺ in stress-induced attenuation of CA1 LTP was examined in hippocampal slices from young rats after exposure to tail suspension stress for 30 s, which significantly increased serum corticosterone. Stress-induced attenuation of CA1 LTP was ameliorated by administration of clioquinol, a membrane permeable zinc chelator, to rats prior to exposure to stress, implying that the reduction of synaptic Zn²⁺ by clioquinol participates in this amelioration. To pursue the involvement of corticosterone-mediated Zn²⁺ signal in the attenuated CA1 LTP by stress, dynamics of synaptic Zn²⁺ was checked in hippocampal slices exposed to corticosterone. Corticosterone increased extracellular Zn²⁺ levels measured with ZnAF-2 dose-dependently, as well as the intracellular Ca²⁺ levels measured with calcium orange AM, suggesting that corticosterone excites zincergic neurons in the hippocampus and increases Zn²⁺ release from the neuron terminals. Intracellular Zn²⁺ levels measured with ZnAF-2DA were also increased dose-dependently, but not in the coexistence of CaEDTA, a membrane-impermeable zinc chelator, suggesting that intracellular Zn²⁺ levels is increased by the influx of extracellular Zn²⁺. Furthermore, corticosterone-induced attenuation of CA1 LTP was abolished in the coexistence of CaEDTA. The present study suggests that corticosterone-mediated increase in postsynaptic Zn²⁺ signal in the cytosolic compartment is involved in the attenuation of CA1 LTP after exposure to acute stress.