Disrupted cross-laminar cortical processing in β amyloid pathology precedes cell death.

Autor: Lison H; Leibniz-Institute for Neurobiology, Brenneckestr. 6, 39118 Magdeburg, Germany., Happel MF; Leibniz-Institute for Neurobiology, Brenneckestr. 6, 39118 Magdeburg, Germany., Schneider F; Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE), c/o Universitätsklinikum Magdeburg, Leipziger Strasse 44/Haus 64, 39120 Magdeburg, Germany., Baldauf K; Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE), c/o Universitätsklinikum Magdeburg, Leipziger Strasse 44/Haus 64, 39120 Magdeburg, Germany., Kerbstat S; Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE), c/o Universitätsklinikum Magdeburg, Leipziger Strasse 44/Haus 64, 39120 Magdeburg, Germany., Seelbinder B; Leibniz-Institute for Neurobiology, Brenneckestr. 6, 39118 Magdeburg, Germany., Schneeberg J; Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE), c/o Universitätsklinikum Magdeburg, Leipziger Strasse 44/Haus 64, 39120 Magdeburg, Germany., Zappe M; Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE), c/o Universitätsklinikum Magdeburg, Leipziger Strasse 44/Haus 64, 39120 Magdeburg, Germany., Goldschmidt J; Leibniz-Institute for Neurobiology, Brenneckestr. 6, 39118 Magdeburg, Germany., Budinger E; Leibniz-Institute for Neurobiology, Brenneckestr. 6, 39118 Magdeburg, Germany., Schröder UH; Leibniz-Institute for Neurobiology, Brenneckestr. 6, 39118 Magdeburg, Germany., Ohl FW; Leibniz-Institute for Neurobiology, Brenneckestr. 6, 39118 Magdeburg, Germany., Schilling S; Probiodrug AG, Weinbergweg 22, 06120 Halle (Saale), Germany., Demuth HU; Probiodrug AG, Weinbergweg 22, 06120 Halle (Saale), Germany., Scheich H; Leibniz-Institute for Neurobiology, Brenneckestr. 6, 39118 Magdeburg, Germany., Reymann KG; Leibniz-Institute for Neurobiology, Brenneckestr. 6, 39118 Magdeburg, Germany; Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE), c/o Universitätsklinikum Magdeburg, Leipziger Strasse 44/Haus 64, 39120 Magdeburg, Germany., Rönicke R; Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE), c/o Universitätsklinikum Magdeburg, Leipziger Strasse 44/Haus 64, 39120 Magdeburg, Germany; Department of Clinical Chemistry and Pathobiochemistry, Otto-von-Guericke-University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany. Electronic address: raik.roenicke@med.ovgu.de.
Jazyk: angličtina
Zdroj: Neurobiology of disease [Neurobiol Dis] 2014 Mar; Vol. 63, pp. 62-73. Date of Electronic Publication: 2013 Nov 27.
DOI: 10.1016/j.nbd.2013.11.014
Abstrakt: Disruption of neuronal networks in the Alzheimer-afflicted brain is increasingly recognized as a key correlate of cognitive and memory decline in Alzheimer patients. We hypothesized that functional synaptic disconnections within cortical columnar microcircuits by pathological β-amyloid accumulation, rather than cell death, initially causes the cognitive impairments. During development of cortical β-amyloidosis with still few plaques in the transgenic 5xFAD mouse model single cell resolution mapping of neuronal thallium uptake revealed that electrical activity of pyramidal cells breaks down throughout infragranular cortical layer V long before cell death occurs. Treatment of 5xFAD mice with the glutaminyl cyclase inhibitor, PQ 529, partially prevented the decline of pyramidal cell activity, indicating pyroglutamate-modified forms, potentially mixed oligomers of Aβ are contributing to neuronal impairment. Laminar investigation of cortical circuit dysfunction with current source density analysis identified an early loss of excitatory synaptic input in infragranular layers, linked to pathological recurrent activations in supragranular layers. This specific disruption of normal cross-laminar cortical processing coincided with a decline of contextual fear learning.
(Copyright © 2013 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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