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

Luis M. Craveiro, Oliver Weinmann, Bernd Roschitzki, Roman R. Gonzenbach, Björn Zörner, Laura Montani, Kay Yan Benjamin Yee, Joram Feldon, Roman Willi, Martin E. Schwab

Research output: Journal article publicationJournal articleAcademic researchpeer-review

11 Citations (Scopus)

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 4. weeks. 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 4. weeks of continuous administration.
Original languageEnglish
Pages (from-to)52-68
Number of pages17
JournalExperimental Neurology
Volume250
DOIs
Publication statusPublished - 1 Dec 2013
Externally publishedYes

Keywords

  • Axonal growth
  • Behavior
  • Clinical
  • Hippocampus
  • Nogo-A
  • Plasticity
  • Proteomics

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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