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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-41172

Zagrebelsky, M; Schweigreiter, R; Bandtlow, C E; Schwab, M E; Korte, M (2010). Nogo-A stabilizes the architecture of hippocampal neurons. Journal of Neuroscience, 30(40):13220-13234.

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Abstract

Although the role of myelin-derived Nogo-A as an inhibitor of axonal regeneration after CNS injury has been thoroughly described, its physiological function in the adult, uninjured CNS is less well known. We address this question in the hippocampus, where Nogo-A is expressed by neurons as well as oligodendrocytes. We used 21 d in vitro slice cultures of neonatal hippocampus where we applied different approaches to interfere with Nogo-A signaling and expression and analyze their effects on the dendritic and axonal architecture of pyramidal cells. Neutralization of Nogo-A by function-blocking antibodies induced a major alteration in the dendrite structure of hippocampal pyramidal neurons. Although spine density was not influenced by Nogo-A neutralization, spine type distribution was shifted toward a more immature phenotype. Axonal complexity and length were greatly increased. Nogo-A KO mice revealed a weak dendritic phenotype resembling the effect of the antibody treatment. To discriminate a possible cell-autonomous role of Nogo-A from an environmental, receptor-mediated function, we studied the effects of short hairpin RNA-induced knockdown of Nogo-A or NgR1, a prominent Nogo-A receptor, within individual neurons. Knockdown of Nogo-A reproduced part of the dendritic and none of the spine or axon alterations. However, downregulation of NgR1 replicated the dendritic, the axonal, and the spine alterations observed after Nogo-A neutralization. Together, our results demonstrate that Nogo-A plays a major role in stabilizing and maintaining the architecture of hippocampal pyramidal neurons. Mechanistically, although the majority of the activity of Nogo-A relies on a receptor-mediated mechanism involving NgR1, its cell-autonomous function plays a minor role.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Brain Research Institute
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:October 2010
Deposited On:05 Jan 2011 09:17
Last Modified:17 Jan 2014 04:53
Publisher:Society for Neuroscience
ISSN:0270-6474
Additional Information:Holder of copyright: The Society for Neuroscience
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:10.1523/JNEUROSCI.1044-10.2010
PubMed ID:20926648

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