Bone morphogenetic proteins 4, 6, and 7 are up-regulated in mouse spinal cord during experimental autoimmune encephalomyelitis

Jahan Ara, Jill See, Polina Mamontov, Ashleigh Hahn, Peter Bannerman, David E Pleasure, Judith B. Grinspan

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Although spontaneous remyelination occurs in multiple sclerosis (MS), the extent of myelin repair is often inadequate to restore normal function. Oligodendrocyte precursors remaining in nonremyelinating MS plaques may be restricted by an inhibitory signal. Bone morphogenetic proteins (BMPs) have been implicated as repressors of oligodendrocyte development and inducers of astrogliogenesis. We hypothesized that BMPs are up-regulated in MS lesions and play a role in demyelination and astrogliosis. We examined expression of BMPs in an animal model of MS, chronic experimental autoimmune encephalomyelitis (EAE) induced by the myelin oligodendrocyte glycoprotein (MOG) peptide in C57BL/ 6 mice. By 14 days postimmunization, compared to those of control mice, the lumbar spinal cords of MOG-peptide EAE mice demonstrated prominent astrogliosis, infiltration of inflammatory cells, and disrupted expression of myelin proteins. Quantitative RT-PCR showed that expression of BMP4, BMP6, and BMP7 mRNA increased 2- to 4-fold in the lumbar spinal cords of animals with symptomatic EAE versus in vehicle-treated and untreated controls on days 14, 21, and 42 postimmunization. BMP2 mRNA expression was not altered. BMP4 mRNA was much more abundant in the spinal cords of all animals than was mRNA encoding BMP2, BMP6, and BMP7. Immunoblot analysis confirmed the increased expression of BMP4 in the EAE animals. Immunohistochemistry revealed increased BMP4 immunoreactivity in areas of inflammation in MOG-peptide EAE animals. BMP4 labeling was mostly limited to macrophages but was sometimes associated with astrocytes and oligodendrocytes. These results indicate that members of the BMP family are differentially expressed in adult spinal cord and are up-regulated during EAE.

Original languageEnglish (US)
Pages (from-to)125-135
Number of pages11
JournalJournal of Neuroscience Research
Volume86
Issue number1
DOIs
StatePublished - Jan 2008

Fingerprint

Bone Morphogenetic Protein 6
Bone Morphogenetic Protein 4
Bone Morphogenetic Protein 7
Autoimmune Experimental Encephalomyelitis
Spinal Cord
Bone Morphogenetic Proteins
Myelin-Oligodendrocyte Glycoprotein
Multiple Sclerosis
Oligodendroglia
Messenger RNA
Peptides
Myelin Proteins
Demyelinating Diseases
Myelin Sheath
Inbred C57BL Mouse
Astrocytes
Animal Models
Immunohistochemistry
Macrophages
Inflammation

Keywords

  • Astrocytes
  • Oligodendrocytes
  • Remyelination

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Bone morphogenetic proteins 4, 6, and 7 are up-regulated in mouse spinal cord during experimental autoimmune encephalomyelitis. / Ara, Jahan; See, Jill; Mamontov, Polina; Hahn, Ashleigh; Bannerman, Peter; Pleasure, David E; Grinspan, Judith B.

In: Journal of Neuroscience Research, Vol. 86, No. 1, 01.2008, p. 125-135.

Research output: Contribution to journalArticle

Ara, Jahan ; See, Jill ; Mamontov, Polina ; Hahn, Ashleigh ; Bannerman, Peter ; Pleasure, David E ; Grinspan, Judith B. / Bone morphogenetic proteins 4, 6, and 7 are up-regulated in mouse spinal cord during experimental autoimmune encephalomyelitis. In: Journal of Neuroscience Research. 2008 ; Vol. 86, No. 1. pp. 125-135.
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