Increased demyelination and axonal damage in metallothionein I+II-deficient mice during experimental autoimmune encephalomyelitis.
Metallothioneins I+II (MT-I+II) are antioxidant, neuroprotective factors. We previously showed that MT-I+II deficiency during experimental autoimmune encephalomyelitis (EAE) leads to increased disease incidence and clinical symptoms. Moreover, the inflammatory response of macrophages and T cells, oxidative stress, and apoptotic cell death during EAE were increased by MT-I+II deficiency. We now show for the first time that demyelination and axonal damage are significantly increased in MT-I+II deficient mice during EAE. Furthermore, oligodendroglial regeneration, growth cone formation, and tissue repair including expression of trophic factors were significantly reduced in MT-I+II-deficient mice during EAE. Accordingly, MT-I+II have protective and regenerative roles in the brain.
Penkowa
M
M
Department of Medical Anatomy, The Panum Institute, University of Copenhagen, 2200, Copenhagen, Denmark.
Espejo
C
C
Martínez-Cáceres
E M
EM
Montalban
X
X
Hidalgo
J
J
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology*; D001933:Brain Stem / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D015870:Gene Expression; D020439:Growth Cones / Q000473:pathology; D006133:Growth Substances / Q000378:metabolism; D008668:Metallothionein / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000378:metabolism; D009836:Oligodendroglia / Q000473:pathology; D013116:Spinal Cord / Q000473:pathology
D006133:Growth Substances; D009414:Nerve Growth Factors; D008668:Metallothionein