Excess influx of Zn 2+ into dentate granule cells affects object recognition memory via attenuated LTP

Suzuki, Michitaka; Fujise, Yuki; Tsuchiya, Yuka; Tamano, Haruna; Takeda, Atsüshi

doi:10.1016/j.neuint.2015.05.006

Cited by 32 publications

(14 citation statements)

References 35 publications

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“…It is likely that, as is the case with Cu 2ϩ binding to A␤ , the apparent K d of metal binding to A␤ 1-42 is higher in affinity than to A␤ 1-40 probably due to the perturbed equilibrium caused by the increased self-assembly of A␤ 1-42 oligomers. In vivo LTP at medial perforant pathway-dentate granule cell synapses, which is closely linked to object recognition memory (Takeda et al, 2014a, b;Suzuki et al, 2015), was not affected by perfusion with 1000 nM A␤ 1-42 in ACSF without Zn 2ϩ , but attenuated under preperfusion with 5 nM A␤ 1-42 in ACSF containing 10 nM Zn 2ϩ , as estimated Zn 2ϩ concentration in the brain extracellular compartment under the basal (static) conditions (Frederickson et al, 2006). The attenuation was rescued by extracellular Zn 2ϩ chelation with CaEDTA, whereas the attenuation was not observed under preperfusion with 5 nM A␤ 1-40 in ACSF containing 10 nM Zn 2ϩ .…”

Section: Discussionmentioning

confidence: 99%

Extracellular Zn²⁺ Is Essential for Amyloid β_1–42-Induced Cognitive Decline in the Normal Brain and Its Rescue

et al. 2017

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were not taken up into dentate granule cells under these conditions, consistent with lower affinity of A␤ 1-40 for Zn 2ϩ than A␤ 1-42 . A␤ 1-42 -induced attenuation of LTP was rescued by both CaEDTA and CdCl 2 , and was observed even with 500 pM A␤ 1-42 . A␤ 1-42 injected into the dentate granule cell layer of rats induced a rapid memory disturbance that was also rescued by coinjection of CdCl 2 . The present study supports blocking the formation of Zn-A␤ 1-42 in the extracellular compartment as an effective preventive strategy for Alzheimer's disease.

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Section: Discussionmentioning

confidence: 99%

Extracellular Zn²⁺ Is Essential for Amyloid β_1–42-Induced Cognitive Decline in the Normal Brain and Its Rescue

et al. 2017

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“…It is likely that a low nanomolar concentration of Zn 2+ is necessary for ACSF. Because homeostasis of extracellular Zn 2+ may be linked to that of intracellular Zn 2+ (Takeda and Tamano, ; Suzuki et al, ), it is important to pay more attention to synaptic Zn 2+ dynamics for assessing synaptic function precisely in in vitro slice experiments.…”

Section: Discussionmentioning

confidence: 99%

Modification of hippocampal excitability in brain slices pretreated with a low nanomolar concentration of Zn²⁺

Takeda

Shakushi

Tamano

2015

J of Neuroscience Research

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Synaptic Zn2+ homeostasis may be changed during brain slice preparation. However, much less attention has been paid to Zn2+ in artificial cerebrospinal fluid (ACSF) used for slice experiments than has been paid to Ca2+ . The present study assesses addition of Zn2+ to ACSF, focused on hippocampal excitability after acute brain slice preparation. When the static levels of intracellular Zn2+ and Ca2+ were compared between brain slices prepared with conventional ACSF without Zn2+ and those pretreated with ACSF containing 20 nM ZnCl2 for 1 hr, both levels were almost the same. On the other hand, intracellular Ca2+ levels were significantly increased in the stratum lucidum of the control brain slices after stimulation with high K+, although the increase was significantly suppressed by the pretreatment with ACSF containing Zn2+, suggesting that neuronal excitation is enhanced in brain slices prepared with ACSF without Zn2+. The increase in extracellular Zn2+ level, an index of glutamate release, after stimulation with high K+ was also significantly suppressed by pretreatment with ACSF containing Zn2+. When mossy fiber excitation was assessed in brain slices with FM4-64, an indicator of presynaptic activity, attenuation of FM 4-64 fluorescence based on presynaptic activity was suppressed in the stratum lucidum of brain slices pretreated with ACSF containing Zn2+. The present study indicates that hippocampal excitability is enhanced in brain slices prepared with ACSF without Zn2+. It is likely that a low nanomolar concentration of Zn2+ is necessary for ACSF.

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“…Interestingly, extracellular Zn 2+ influx into hippocampal neurons is increased by not only glutamatergic synapse excitation 23,24) but also extracellular Aβ . 25) Glutamatergic synapse excitation rapidly increases intracellular Zn 2+ through Ca 2+ -permeable AMPA receptors followed by cognitive decline.…”

Section: +mentioning

confidence: 99%

“…Both memory acquisition via LTP induction and memory retention via LTP maintenance are affected after local injection of high K + into the dentate gyrus, which rapidly increases intracellular Zn 2+ in dentate granule cells through Ca 2+ -permeable AMPA receptors. 24,50) Although high K + -induced Zn 2+ influx also affects memory acquisition via LTP induction in the hippocampal CA1, 23) neurogenesisrelated apoptosis, which can be a cause of cognitive decline, may be involved in age-related modification of dentate gyrus function, in addition to the decreased neurogenesis.…”

Section: Modification Of Extracellular Zn 2+ Dy-namics and Its Relatimentioning

confidence: 99%

Is Vulnerability of the Dentate Gyrus to Aging and Amyloid-β<sub>1–42</sub> Neurotoxicity Linked with Modified Extracellular Zn<sup>2+</sup> Dynamics?

Takeda

Tamano

2018

Biological & Pharmaceutical Bulletin

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The basal levels of extracellular Zn 2 are in the range of low nanomolar concentrations in the hippocampus and perhaps increase age-dependently. Extracellular Zn 2 dynamics is critical for cognitive activity and excess influx of extracellular Zn 2 into hippocampal neurons is a known cause of cognitive decline. The dentate gyrus is vulnerable to aging in the hippocampus and affected in the early stage of Alzheimer's disease (AD). The reasons remain unclear. Neurogenesis-related apoptosis may induce non-specific neuronal depolarization by efflux of intracellular K in the dentate gyrus and be markedly increased along with aging. Extracellular Zn 2 influx into dentate granule cells via high K -induced perforant pathway excitation leads to cognitive decline. Modified extracellular Zn 2 dynamics in the dentate gyrus of aged rats is linked with vulnerability to cognitive decline. Amyloid-β 1-42 (Aβ 1-42 ) is a causative candidate for AD pathogenesis. When Aβ 1-42 concentration reaches picomolar in the extracellular compartment in the dentate gyrus, Zn-Aβ 1-42 is formed in the extracellular compartment and rapidly taken up into dentate granule cells, followed by Aβ 1-42 -induced cognitive decline that is due to Zn 2 released from Aβ 1-42 , suggesting that dentate granule cells are sensitive to extracellular Zn 2 -dependent Aβ 1-42 toxicity. This paper deals with proposed vulnerability of the dentate gyrus to aging and Aβ 1-42 neurotoxicity.

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Excess influx of Zn 2+ into dentate granule cells affects object recognition memory via attenuated LTP

Cited by 32 publications

References 35 publications

Extracellular Zn²⁺ Is Essential for Amyloid β_1–42-Induced Cognitive Decline in the Normal Brain and Its Rescue

Extracellular Zn²⁺ Is Essential for Amyloid β_1–42-Induced Cognitive Decline in the Normal Brain and Its Rescue

Modification of hippocampal excitability in brain slices pretreated with a low nanomolar concentration of Zn²⁺

Is Vulnerability of the Dentate Gyrus to Aging and Amyloid-β<sub>1–42</sub> Neurotoxicity Linked with Modified Extracellular Zn<sup>2+</sup> Dynamics?

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Excess influx of Zn 2+ into dentate granule cells affects object recognition memory via attenuated LTP

Cited by 32 publications

References 35 publications

Extracellular Zn2+ Is Essential for Amyloid β1–42-Induced Cognitive Decline in the Normal Brain and Its Rescue

Extracellular Zn2+ Is Essential for Amyloid β1–42-Induced Cognitive Decline in the Normal Brain and Its Rescue

Modification of hippocampal excitability in brain slices pretreated with a low nanomolar concentration of Zn2+

Is Vulnerability of the Dentate Gyrus to Aging and Amyloid-β<sub>1–42</sub> Neurotoxicity Linked with Modified Extracellular Zn<sup>2+</sup> Dynamics?

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Extracellular Zn²⁺ Is Essential for Amyloid β_1–42-Induced Cognitive Decline in the Normal Brain and Its Rescue

Extracellular Zn²⁺ Is Essential for Amyloid β_1–42-Induced Cognitive Decline in the Normal Brain and Its Rescue

Modification of hippocampal excitability in brain slices pretreated with a low nanomolar concentration of Zn²⁺