Transient 5-(4-phenylbutoxy)psoralen (PAP-1) treatment dissociates developing pathologies in autoimmune optic neuritis into two distinct pathology profiles

Martha E. Stokely, Puja Garg, Manzoor Bhat, Peter Koulen

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Discovery of treatments to protect axonal function of neurons and prevent permanent disability associated with progressive multiple sclerosis (MS) has faced the uphill challenge of assessing relatively small changes in accumulated axon damage within a background environment that is disorganized by CNS inflammation. We hypothesized that transient immunosuppression after initiation of MS-like autoimmune mechanisms would disassociate development of MS-like myelinated axon pathology from development of CNS inflammation in a rat model of autoimmune optic neuritis (AON). A rat model of myelin oligodendrocyte glycoprotein peptide-induced AON was transiently treated (on days 3-7 after antigen exposure) with 5-(4-phenylbutoxy)psoralen (PAP-1), an immunomodulatory drug previously shown specifically to suppress proliferation of effector memory T-cells and immunoglobulin class-switched B-cells. Thirteen days after antigen exposure, optic nerves were harvested for quantitative assessment of 12 MS-associated pathologies using microfluorimetry. With one exception, the immunoreactivities (-ir) for eight markers of MS-like neuroinflammation and immune infiltration were significantly reduced (P < 0.05) by transient PAP-1 treatment, often to levels significantly below those detected in normal control rat optic nerves. With one exception, four immunoreactive markers of MS-like myelinated axon pathology were detected at levels indicating increased axon/myelin pathology compared with vehicle-treated rats with AON (P < 0.05). These data suggest the conclusion that early causative mechanisms in CNS autoimmunity initiate signaling mechanisms that diverge into two separate pathways, one that is strongly associated with inflammatory responses and one that is associated predominantly with disturbed axon-myelin interactions and impaired fast axonal transport.

Original languageEnglish (US)
Pages (from-to)2111-2124
Number of pages14
JournalJournal of Neuroscience Research
Volume86
Issue number9
DOIs
StatePublished - Jul 2008
Externally publishedYes

Fingerprint

Optic Neuritis
Multiple Sclerosis
Axons
Pathology
Optic Nerve
Myelin Sheath
Therapeutics
Cytophotometry
Inflammation
Antigens
Axonal Transport
Immunoglobulin Isotypes
Autoimmunity
Immunosuppression
5-(4-phenylbutoxy)psoralen
B-Lymphocytes
T-Lymphocytes
Neurons
Peptides
Pharmaceutical Preparations

Keywords

  • Autoimmune optic neuritis
  • Experimental
  • Myelinated axon pathology

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Transient 5-(4-phenylbutoxy)psoralen (PAP-1) treatment dissociates developing pathologies in autoimmune optic neuritis into two distinct pathology profiles. / Stokely, Martha E.; Garg, Puja; Bhat, Manzoor; Koulen, Peter.

In: Journal of Neuroscience Research, Vol. 86, No. 9, 07.2008, p. 2111-2124.

Research output: Contribution to journalArticle

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