Nogo Receptor Inhibition Enhances Functional Recovery following Lysolecithin-Induced Demyelination in Mouse Optic Chiasm

Autor: Barbara A. Demeneix, Ghislaine Morvan-Dubois, Mohammad Javan, Fereshteh Pourabdolhossein, Sabah Mozafari, Jacqueline Pierre-Simons, Alejandra Lopez-Juarez, Javad Mirnajafi-Zadeh
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Male
Pathology
Time Factors
Physiology
lcsh:Medicine
Optic chiasm
Myelin
Mice
Cell Movement
Nogo Receptor 1
Medicine and Health Sciences
Basic Helix-Loop-Helix Transcription Factors
RNA
Small Interfering
lcsh:Science
Receptor
Myelin Sheath
Multidisciplinary
Stem Cells
medicine.anatomical_structure
Neurology
Optic Chiasm
Stem cell
Myelin Proteins
Research Article
medicine.medical_specialty
Microinjections
Central nervous system
Nerve Tissue Proteins
Receptors
Cell Surface
Inhibitory postsynaptic potential
GPI-Linked Proteins
medicine
Animals
Remyelination
Cell Proliferation
Injections
Intraventricular
business.industry
lcsh:R
Biology and Life Sciences
Lysophosphatidylcholines
Recovery of Function
Oligodendrocyte Transcription Factor 2
Mice
Inbred C57BL
Bromodeoxyuridine
Gene Expression Regulation
Evoked Potentials
Visual
lcsh:Q
business
Neuroscience
Demyelinating Diseases
Zdroj: PLoS ONE
PLoS ONE, Vol 9, Iss 9, p e106378 (2014)
ISSN: 1932-6203
Popis: Background Inhibitory factors have been implicated in the failure of remyelination in demyelinating diseases. Myelin associated inhibitors act through a common receptor called Nogo receptor (NgR) that plays critical inhibitory roles in CNS plasticity. Here we investigated the effects of abrogating NgR inhibition in a non-immune model of focal demyelination in adult mouse optic chiasm. Methodology/Principal Findings A focal area of demyelination was induced in adult mouse optic chiasm by microinjection of lysolecithin. To knock down NgR levels, siRNAs against NgR were intracerebroventricularly administered via a permanent cannula over 14 days, Functional changes were monitored by electrophysiological recording of latency of visual evoked potentials (VEPs). Histological analysis was carried out 3, 7 and 14 days post demyelination lesion. To assess the effect of NgR inhibition on precursor cell repopulation, BrdU was administered to the animals prior to the demyelination induction. Inhibition of NgR significantly restored VEPs responses following optic chiasm demyelination. These findings were confirmed histologically by myelin specific staining. siNgR application resulted in a smaller lesion size compared to control. NgR inhibition significantly increased the numbers of BrdU+/Olig2+ progenitor cells in the lesioned area and in the neurogenic zone of the third ventricle. These progenitor cells (Olig2+ or GFAP+) migrated away from this area as a function of time. Conclusions/Significance Our results show that inhibition of NgR facilitate myelin repair in the demyelinated chiasm, with enhanced recruitment of proliferating cells to the lesion site. Thus, antagonizing NgR function could have therapeutic potential for demyelinating disorders such as Multiple Sclerosis.
Databáze: OpenAIRE
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