Is Vulnerability of the Dentate Gyrus to Aging and Amyloid-β1-42 Neurotoxicity Linked with Modified Extracellular Zn2+ Dynamics?

Abstract:

:The basal levels of extracellular Zn2+ are in the range of low nanomolar concentrations in the hippocampus and perhaps increase age-dependently. Extracellular Zn2+ dynamics is critical for cognitive activity and excess influx of extracellular Zn2+ 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 Zn2+ influx into dentate granule cells via high K+-induced perforant pathway excitation leads to cognitive decline. Modified extracellular Zn2+ dynamics in the dentate gyrus of aged rats is linked with vulnerability to cognitive decline. Amyloid-β1-42 (Aβ1-42) is a causative candidate for AD pathogenesis. When Aβ1-42 concentration reaches picomolar in the extracellular compartment in the dentate gyrus, Zn-Aβ1-42 is formed in the extracellular compartment and rapidly taken up into dentate granule cells, followed by Aβ1-42-induced cognitive decline that is due to Zn2+ released from Aβ1-42, suggesting that dentate granule cells are sensitive to extracellular Zn2+-dependent Aβ1-42 toxicity. This paper deals with proposed vulnerability of the dentate gyrus to aging and Aβ1-42 neurotoxicity.

journal_name

Biol Pharm Bull

authors

Takeda A,Tamano H

doi

10.1248/bpb.b17-00871

subject

Has Abstract

pub_date

2018-01-01 00:00:00

pages

995-1000

issue

7

eissn

0918-6158

issn

1347-5215

journal_volume

41

pub_type

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