Header

UZH-Logo

Maintenance Infos

Infusion of anti-Nogo-A antibodies in adult rats increases growth and synapse related proteins in the absence of behavioral alterations


Craveiro, Luis M; Weinmann, Oliver; Roschitzki, Bernd; Gonzenbach, Roman R; Zörner, Björn; Montani, Laura; Yee, Benjamin K; Feldon, Joram; Willi, Roman; Schwab, Martin E (2013). Infusion of anti-Nogo-A antibodies in adult rats increases growth and synapse related proteins in the absence of behavioral alterations. Experimental Neurology, 250:52-68.

Abstract

Restricted structural re-growth in the adult CNS is a major limitation to fully functional recovery following extensive CNS trauma. This limitation is partly due to the presence of growth inhibitory proteins, in particular, Nogo-A. Pre-clinical studies have demonstrated that intrathecally infused anti-Nogo-A antibodies are readily distributed via the cerebrospinal fluid penetrating throughout the spinal cord and brain, where they promote sprouting, axonal regeneration and improved functional recovery after CNS injury. Whether anti-Nogo-A treatments of intact animals might induce behavioral alterations has not been systematically tested. This is addressed here in an adult rat model of chronic intrathecal infusion of function-blocking anti-Nogo-A antibodies for 2 to 4weeks. We observed by proteomic and immunohistochemical techniques that chronic Nogo-A neutralization in the intact CNS increased expression of cytoskeletal, fiber-growth-related, and synaptic proteins in the hippocampus, a brain region which might be particularly sensitive to Nogo-A depletion due to the high expression level of Nogo-A. Despite such molecular and proteomic changes, Nogo-A blockade was not associated with any pronounced cognitive-behavioral changes indicative of hippocampal functional deficiency across several critical tests. Our results suggest that the plastic changes induced by Nogo-A blockade in the adult hippocampus are counter-balanced by homeostatic mechanisms in the intact and the injured CNS. The data indicate that anti-Nogo-A therapy appears safe in the adult CNS over 4weeks of continuous administration.

Abstract

Restricted structural re-growth in the adult CNS is a major limitation to fully functional recovery following extensive CNS trauma. This limitation is partly due to the presence of growth inhibitory proteins, in particular, Nogo-A. Pre-clinical studies have demonstrated that intrathecally infused anti-Nogo-A antibodies are readily distributed via the cerebrospinal fluid penetrating throughout the spinal cord and brain, where they promote sprouting, axonal regeneration and improved functional recovery after CNS injury. Whether anti-Nogo-A treatments of intact animals might induce behavioral alterations has not been systematically tested. This is addressed here in an adult rat model of chronic intrathecal infusion of function-blocking anti-Nogo-A antibodies for 2 to 4weeks. We observed by proteomic and immunohistochemical techniques that chronic Nogo-A neutralization in the intact CNS increased expression of cytoskeletal, fiber-growth-related, and synaptic proteins in the hippocampus, a brain region which might be particularly sensitive to Nogo-A depletion due to the high expression level of Nogo-A. Despite such molecular and proteomic changes, Nogo-A blockade was not associated with any pronounced cognitive-behavioral changes indicative of hippocampal functional deficiency across several critical tests. Our results suggest that the plastic changes induced by Nogo-A blockade in the adult hippocampus are counter-balanced by homeostatic mechanisms in the intact and the injured CNS. The data indicate that anti-Nogo-A therapy appears safe in the adult CNS over 4weeks of continuous administration.

Statistics

Citations

9 citations in Web of Science®
9 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

0 downloads since deposited on 18 Dec 2013
0 downloads since 12 months

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Functional Genomics Center Zurich
04 Faculty of Medicine > Brain Research Institute
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:13 December 2013
Deposited On:18 Dec 2013 13:15
Last Modified:08 Dec 2017 01:19
Publisher:Elsevier
ISSN:0014-4886
Publisher DOI:https://doi.org/10.1016/j.expneurol.2013.09.015
PubMed ID:24076004

Download