Enhanced Expression of Trib3 during the Development of Myelin Breakdown in dmy Myelin Mutant Rats

• Published in: PloS one Vol. 11; no. 12; p. e0168250
• Main Authors: Shimotsuma, Yukako, Tanaka, Miyuu, Izawa, Takeshi, Yamate, Jyoji, Kuwamura, Mitsuru
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 15.12.2016; Public Library of Science (PLoS)
• Subjects: Age; Animals; Apoptosis; Ataxia; Biology and Life Sciences; Breakdown; Breakdowns; Central nervous system; Coronary vessels; Demyelinating diseases; Demyelinating Diseases - genetics; Demyelinating Diseases - pathology; Demyelination; Development and progression; Endoplasmic reticulum; Female; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Developmental; Genetic aspects; Golgi apparatus; Health aspects; Homology; Immunofluorescence; Kinases; Laboratories; Magnesium; Male; Medicine and Health Sciences; Microarray Analysis; mRNA; Multiple sclerosis; Mutation; Myelin; Myelin Sheath - genetics; Myelin Sheath - metabolism; Myelin Sheath - pathology; Nervous system; Oligodendrocytes; Pathogenesis; Pathology; Phosphotransferases; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Protein-Serine-Threonine Kinases - genetics; Proteins; Rats; Rats, Mutant Strains; Rats, Transgenic; Research and Analysis Methods; Rodents; Spinal cord; Up-Regulation - genetics; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0168250

The demyelination (dmy) rat exhibits hind limb ataxia and severe myelin breakdown in the central nervous system. The causative gene of dmy rats is the MRS2 magnesium transporter gene. Tribbles homolog 3 (Trib3) is a pseudokinase molecule that modifies certain signal pathways, and its expression is increased in response to various stresses. Here we sought to clarify the mechanism of myelin breakdown by focusing Trib3, which is remarkably up-regulated in dmy rats. The expression of Trib3 mRNA was significantly increased at 4, 5, 6, 7 and 8 weeks of age in the dmy rats, prior to the prominent myelin breakdown between 7 and 10 weeks of age. The expression level of Trib3 was increased concurrently with the progression of the clinical and pathological conditions in the dmy rats. Double immunofluorescence demonstrated that TRIB3 was mainly expressed in neurons and oligodendrocytes and localized in the Golgi apparatus. Our findings indicate that Trib3 may be associated with the pathogenic mechanism of dmy rats.