Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
2.
Br J Pharmacol ; 172(7): 1769-82, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25521311

ABSTRACT

BACKGROUND AND PURPOSE: Selective agonists of the sigma-1 receptor (σ1 protein) are generally reported to protect against neuronal damage and modulate oligodendrocyte differentiation. Human and rodent lymphocytes possess saturable, high-affinity binding sites for compounds binding to the σ1 protein and potential immunomodulatory properties have been described for σ1 protein ligands. Experimental autoimmune encephalomyelitis (EAE) is recognized as a valuable model of the inflammatory aspects of multiple sclerosis (MS). Here, we have assessed the role of a σ1 protein agonist, containing the tetrahydroisoquinoline-hydantoin structure, in EAE. EXPERIMENTAL APPROACH: EAE was induced in SJL/J female mice by active immunization with myelin proteolipid protein (PLP)139-151 peptide. The σ1 protein agonist was injected i.p. at the time of immunization (day 0). Disease severity was assessed clinically and by histopathological evaluation of the CNS. Phenotyping of B-cell subsets and regulatory T-cells were performed by flow cytometry in spleen and cervical lymph nodes. KEY RESULTS: Prophylactic treatment of EAE mice with the σ1 protein agonist prevented mononuclear cell accumulation and demyelination in brain and spinal cord and increased T2 B-cells and regulatory T-cells, resulting in an overall reduction in the clinical progression of EAE. CONCLUSIONS AND IMPLICATIONS: This σ1 protein agonist, containing the tetrahydroisoquinoline-hydantoin structure, decreased the magnitude of inflammation in EAE. This effect was associated with increased proportions of B-cell subsets and regulatory T-cells with potential immunoregulatory functions. Targeting of the σ1 protein might thus provide new therapeutic opportunities in MS.


Subject(s)
Encephalomyelitis, Autoimmune, Experimental/drug therapy , Multiple Sclerosis/drug therapy , Neuroprotective Agents/therapeutic use , Receptors, sigma/agonists , Animals , B-Lymphocytes/immunology , Brain/drug effects , Brain/pathology , Cytokines/blood , Encephalomyelitis, Autoimmune, Experimental/blood , Encephalomyelitis, Autoimmune, Experimental/immunology , Encephalomyelitis, Autoimmune, Experimental/pathology , Female , Immunoglobulin G/blood , Lymph Nodes/drug effects , Lymph Nodes/immunology , Mice , Multiple Sclerosis/blood , Multiple Sclerosis/immunology , Multiple Sclerosis/pathology , Myelin Proteolipid Protein/immunology , Neuroprotective Agents/pharmacology , Peptide Fragments/immunology , Spinal Cord/drug effects , Spinal Cord/pathology , Spleen/drug effects , Spleen/immunology , T-Lymphocytes, Regulatory/immunology , Sigma-1 Receptor
SELECTION OF CITATIONS
SEARCH DETAIL
...