title: Mice devoid of Tau have increased susceptibility to neuronal damage in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis.
abstract: The abundant axonal microtubule-associated protein tau regulates microtubule and actin dynamics, thereby contributing to normal neuronal function. We examined whether mice deficient in tau (Tau(-/-)) or with high levels of human tau differ from wild-type (WT) mice in their susceptibility to neuroaxonal injury in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. After sensitization with MOG35-55, there was no difference in clinical disease course between human tau and WT mice, but Tau mice had more severe clinical disease and significantly more axonal damage in spinal cord white matter than those in WT mice. Axonal damage in gray matter correlated with clinical severity in individual mice. By immunoblot analysis, the early microtubule-associated protein-1b was increased 2-fold in the spinal cords of Tau mice with chronic experimental autoimmune encephalomyelitis versus naive Tau mice. This difference was not detected in comparable WT animals, which suggests that there was compensation for the loss of tau in the deficient mice. In addition, levels of the growth arrest-specific protein 7b, a tau-binding protein that is stabilized when bound to tau, were higher in WT than those in Tau(-/-) spinal cord samples. These data indicate that loss of tau exacerbates experimental autoimmune encephalomyelitis and suggest that maintaining tau integrity might reduce the axonal damage that occurs in inflammatory neurodegenerative diseases such as multiple sclerosis.
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Jason G
authors.initials: JG
authors.lastname: Weinger
authors.forename: Peter
authors.initials: P
authors.lastname: Davies
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Acker
authors.forename: Celia F
authors.initials: CF
authors.lastname: Brosnan
authors.forename: Vladislav
authors.initials: V
authors.lastname: Tsiperson
authors.forename: Ashrei
authors.initials: A
authors.lastname: Bayewitz
authors.forename: Bridget
authors.initials: B
authors.lastname: Shafit-Zagardo
mesh_terms: D000367:Age Factors; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000503:physiopathology*; D005620:Freund's Adjuvant / Q000009:adverse effects; D005786:Gene Expression Regulation / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006023:Glycoproteins / Q000009:adverse effects*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D063308:Myelin-Oligodendrocyte Glycoprotein; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D010243:Paralysis / Q000235:genetics; D010446:Peptide Fragments / Q000009:adverse effects*; D010766:Phosphorylation / Q000502:physiology; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology*; D016875:tau Proteins / Q000172:deficiency*
chemical_list: D003598:Cytoskeletal Proteins; D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); D016875:tau Proteins; D005620:Freund's Adjuvant