title: Increased phosphorylation of cyclic AMP response element-binding protein in the spinal cord of Lewis rats with experimental autoimmune encephalomyelitis.
abstract: To investigate whether the phosphorylation of cyclic AMP response element-binding protein (CREB) is implicated in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), the change in the level of CREB phosphorylation was analyzed in the spinal cord of Lewis rats with EAE. Western blot analysis showed that the phosphorylation of CREB in the spinal cord of rats increased significantly at the peak stage of EAE compared with the controls (p<0.05) and declined significantly in the recovery stage (p<0.05). Immunohistochemistry showed that the phosphorylated form of CREB (p-CREB) was constitutively immunostained in few astrocytes and dorsal horn neurons in the spinal cord of normal rats. In the EAE-affected spinal cord, p-CREB was mainly found in ED1-positive macrophages at the peak stage of EAE, and the number of p-CREB-immunopositive astrocytes was markedly increased in the spinal cord with EAE compared with the controls. Moreover, p-CREB immunoreactivity of sensory neurons, which are closely associated with neuropathic pain, was significantly increased in the dorsal horns at the peak stage of EAE. Based on these results, we suggest that the increased phosphorylation of CREB in EAE lesions was mainly attributable to the infiltration of inflammatory cells and astrogliosis, possibly activating gene transcription, and that its increase in the sensory neurons in the dorsal horns is involved in the generation of neuropathic pain in the rat EAE model.
authors.affiliation: Department of Veterinary Medicine and Applied Radiological Science Research Institute, Cheju National University, Jeju 690-756, South Korea.
authors.forename: Heechul
authors.initials: H
authors.lastname: Kim
authors.forename: Changjong
authors.initials: C
authors.lastname: Moon
authors.forename: Meejung
authors.initials: M
authors.lastname: Ahn
authors.forename: Yongduk
authors.initials: Y
authors.lastname: Lee
authors.forename: Seungjoon
authors.initials: S
authors.lastname: Kim
authors.forename: Yoh
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Chang-Sung
authors.initials: CS
authors.lastname: Koh
authors.forename: Moon-Doo
authors.initials: MD
authors.lastname: Kim
authors.forename: Taekyun
authors.initials: T
authors.lastname: Shin
mesh_terms: D051697:Activating Transcription Factor 1 / Q000378:metabolism; D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D053331:Ectodysplasins / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D005312:Fetal Blood / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008297:Male; D004676:Myelin Basic Protein; D010766:Phosphorylation; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism
chemical_list: D051697:Activating Transcription Factor 1; D017362:Cyclic AMP Response Element-Binding Protein; D053331:Ectodysplasins; D005904:Glial Fibrillary Acidic Protein; D004676:Myelin Basic Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta