Role of metallothionein-III following central nervous system damage

We evaluated the physiological relevance of metallothionein-III (MT-III) in the central nervous system following damage caused by a focal cryolesion onto the cortex by studying Mt3-null mice. In normal mice, dramatic astrogliosis and microgliosis and T-cell infiltration were observed in the area sur...

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Main Authors: Javier Carrasco, Milena Penkowa, Mercedes Giralt, Jordi Camats, Amalia Molinero, Iain L. Campbell, Richard D. Palmiter, Juan Hidalgo
Format: Article
Language:English
Published: Elsevier 2003-06-01
Series:Neurobiology of Disease
Online Access:http://www.sciencedirect.com/science/article/pii/S0969996103000159
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author Javier Carrasco
Milena Penkowa
Mercedes Giralt
Jordi Camats
Amalia Molinero
Iain L. Campbell
Richard D. Palmiter
Juan Hidalgo
author_facet Javier Carrasco
Milena Penkowa
Mercedes Giralt
Jordi Camats
Amalia Molinero
Iain L. Campbell
Richard D. Palmiter
Juan Hidalgo
author_sort Javier Carrasco
collection DOAJ
description We evaluated the physiological relevance of metallothionein-III (MT-III) in the central nervous system following damage caused by a focal cryolesion onto the cortex by studying Mt3-null mice. In normal mice, dramatic astrogliosis and microgliosis and T-cell infiltration were observed in the area surrounding the lesioned tissue, along with signs of increased oxidative stress and apoptosis. There was also significant upregulation of cytokines/growth factors such as tumor necrosis factor-α, interleukin (IL)-1 α/β, and IL-6 as measured by ribonuclease protection assay. Mt3-null mice did not differ from control mice in these responses, in sharp contrast to results obtained in Mt1- Mt2-null mice. In contrast, Mt3-null mice showed increased expression of several neurotrophins as well as of the neuronal sprouting factor GAP-43. Thus, unlike MT-I and MT-II, MT-III does not affect the inflammatory response elicited in the central nervous system by a cryoinjury, nor does it serve an important antioxidant role, but it may influence neuronal regeneration during the recovery process.
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spelling doaj.art-8f9a25f27563409a83d67ccb1338e7882022-12-21T22:42:42ZengElsevierNeurobiology of Disease1095-953X2003-06-011312236Role of metallothionein-III following central nervous system damageJavier Carrasco0Milena Penkowa1Mercedes Giralt2Jordi Camats3Amalia Molinero4Iain L. Campbell5Richard D. Palmiter6Juan Hidalgo7Institute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Animal Physiology Unit, Faculty of Sciences, Autonomous University of Barcelona, Bellaterra, Barcelona, Spain 08193; Department of Medical Anatomy, The Panum Institute, University of Copenhagen, DK-2200 Copenhagen, Denmark; Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Department of Biochemistry, University of Washington, Seattle, WA 98195, USAInstitute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Animal Physiology Unit, Faculty of Sciences, Autonomous University of Barcelona, Bellaterra, Barcelona, Spain 08193; Department of Medical Anatomy, The Panum Institute, University of Copenhagen, DK-2200 Copenhagen, Denmark; Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Department of Biochemistry, University of Washington, Seattle, WA 98195, USAInstitute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Animal Physiology Unit, Faculty of Sciences, Autonomous University of Barcelona, Bellaterra, Barcelona, Spain 08193; Department of Medical Anatomy, The Panum Institute, University of Copenhagen, DK-2200 Copenhagen, Denmark; Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Department of Biochemistry, University of Washington, Seattle, WA 98195, USAInstitute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Animal Physiology Unit, Faculty of Sciences, Autonomous University of Barcelona, Bellaterra, Barcelona, Spain 08193; Department of Medical Anatomy, The Panum Institute, University of Copenhagen, DK-2200 Copenhagen, Denmark; Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Department of Biochemistry, University of Washington, Seattle, WA 98195, USAInstitute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Animal Physiology Unit, Faculty of Sciences, Autonomous University of Barcelona, Bellaterra, Barcelona, Spain 08193; Department of Medical Anatomy, The Panum Institute, University of Copenhagen, DK-2200 Copenhagen, Denmark; Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Department of Biochemistry, University of Washington, Seattle, WA 98195, USAInstitute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Animal Physiology Unit, Faculty of Sciences, Autonomous University of Barcelona, Bellaterra, Barcelona, Spain 08193; Department of Medical Anatomy, The Panum Institute, University of Copenhagen, DK-2200 Copenhagen, Denmark; Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Department of Biochemistry, University of Washington, Seattle, WA 98195, USAInstitute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Animal Physiology Unit, Faculty of Sciences, Autonomous University of Barcelona, Bellaterra, Barcelona, Spain 08193; Department of Medical Anatomy, The Panum Institute, University of Copenhagen, DK-2200 Copenhagen, Denmark; Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Department of Biochemistry, University of Washington, Seattle, WA 98195, USAInstitute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Animal Physiology Unit, Faculty of Sciences, Autonomous University of Barcelona, Bellaterra, Barcelona, Spain 08193; Department of Medical Anatomy, The Panum Institute, University of Copenhagen, DK-2200 Copenhagen, Denmark; Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Department of Biochemistry, University of Washington, Seattle, WA 98195, USAWe evaluated the physiological relevance of metallothionein-III (MT-III) in the central nervous system following damage caused by a focal cryolesion onto the cortex by studying Mt3-null mice. In normal mice, dramatic astrogliosis and microgliosis and T-cell infiltration were observed in the area surrounding the lesioned tissue, along with signs of increased oxidative stress and apoptosis. There was also significant upregulation of cytokines/growth factors such as tumor necrosis factor-α, interleukin (IL)-1 α/β, and IL-6 as measured by ribonuclease protection assay. Mt3-null mice did not differ from control mice in these responses, in sharp contrast to results obtained in Mt1- Mt2-null mice. In contrast, Mt3-null mice showed increased expression of several neurotrophins as well as of the neuronal sprouting factor GAP-43. Thus, unlike MT-I and MT-II, MT-III does not affect the inflammatory response elicited in the central nervous system by a cryoinjury, nor does it serve an important antioxidant role, but it may influence neuronal regeneration during the recovery process.http://www.sciencedirect.com/science/article/pii/S0969996103000159
spellingShingle Javier Carrasco
Milena Penkowa
Mercedes Giralt
Jordi Camats
Amalia Molinero
Iain L. Campbell
Richard D. Palmiter
Juan Hidalgo
Role of metallothionein-III following central nervous system damage
Neurobiology of Disease
title Role of metallothionein-III following central nervous system damage
title_full Role of metallothionein-III following central nervous system damage
title_fullStr Role of metallothionein-III following central nervous system damage
title_full_unstemmed Role of metallothionein-III following central nervous system damage
title_short Role of metallothionein-III following central nervous system damage
title_sort role of metallothionein iii following central nervous system damage
url http://www.sciencedirect.com/science/article/pii/S0969996103000159
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