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The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.

Amyloid β Oligomers (Aβ 1–42 Globulomer) Suppress Spontaneous Synaptic Activity by Inhibition of P/Q-Type Calcium Currents

Nimmrich, Volker, Grimm, Christiane, Draguhn, Andreas, Barghorn, Stefan, Lehmann, Alexander, Schoemaker, Hans, Hillen, Heinz, Gross, Gerhard, Ebert, Ulrich, Bruehl, Claus·2008·The Journal of Neuroscience
DOI 10.1523/jneurosci.4771-07.2008
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Abstract

Abnormal accumulation of soluble oligomers of amyloid β (Aβ) is believed to cause malfunctioning of neurons in Alzheimer's disease. It has been shown that Aβ oligomers impair synaptic plasticity, thereby altering the ability of the neuron to store information. We examined the underlying cellular mechanism of Aβ oligomer-induced synaptic modifications by using a recently described stable oligomeric Aβ preparation called “Aβ 1–42 globulomer.” Synthetically prepared Aβ 1–42 globulomer has been shown to localize to neurons and impairs long-term potentiation (Barghorn et al., 2005). Here, we demonstrate that Aβ 1–42 globulomer does not affect intrinsic neuronal properties, as assessed by measuring input resistance and discharge characteristics, excluding an unspecific alteration of membrane properties. We provide evidence that Aβ 1–42 globulomer, at concentrations as low as 8 n m , specifically suppresses spontaneous synaptic activity resulting from a reduction of vesicular release at terminals of both GABAergic and glutamatergic synapses. EPSCs and IPSCs were primarily unaffected. A detailed search for the precise molecular target of Aβ 1–42 globulomer revealed a specific inhibition of presynaptic P/Q calcium currents, whereas other voltage-activated calcium currents remained unaltered. Because intact P/Q calcium currents are needed for synaptic plasticity, the disruption of such currents by Aβ 1–42 globulomer may cause deficits in cellular mechanisms of information storage in brains of Alzheimer's disease patients. The inhibitory effect of Aβ 1–42 globulomer on synaptic vesicle release could be reversed by roscovitine, a specific enhancer of P/Q currents. Selective enhancement of the P/Q calcium current may provide a promising strategy in the treatment of Alzheimer's disease.

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  • Decreased NMDA and AMPA currents may be induced by increase of soluble Aβ oligomers, but not Aβ deposits, in the double mutant brain.

    “Our data corroborate with the view that the decreased NMDA and AMPA currents may be induced by the increase of soluble Aβ oligomers, but not Aβ deposits, in the double mutant brain (Nimmrich et al., 2008; Selkoe, 2008)”

    From VPS35 haploinsufficiency increases Alzheimer’s disease neuropathology (2011) · cites this paper as Nimmrich et al., 2008

    The Introduction says soluble Aβ forms, rather than plaques, are associated with impairment, and the Results report that an Aβ oligomer reduces excitatory synaptic activity in cultured hippocampal neurons. But the Discussion says the study found no indication that its oligomer directly affects NMDA receptors. It does not establish decreased NMDA and AMPA currents caused by soluble oligomers rather than deposits in a double-mutant brain. Page numbers are unavailable in our copy. (LLM, conf=0.86)

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Research works printed but not linked: 20

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Metadata

Authors
Nimmrich, V., Grimm, C., Draguhn, A., Barghorn, S., Lehmann, A., Schoemaker, H., Hillen, H., Gross, G., Ebert, U., & Bruehl, C.
Venue
The Journal of Neuroscience
Publisher
Society for Neuroscience
Published
2008-01-23
Volume
28
Issue
4
Pages
788-797
ISSN
  • 0270-6474
  • 1529-2401
DOI
10.1523/jneurosci.4771-07.2008
Cited by
210
References
10
Language
en
Licence
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 182 d)

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