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 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-alpha, interleukin (IL)-1 alpha/beta, 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.
Carrasco
Javier
J
Institute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Animal Physiology Unit, Faculty of Sciences, Autonomous University of Barcelona, Bellaterra, Barcelona, Spain 08193.
Penkowa
Milena
M
Giralt
Mercedes
M
Camats
Jordi
J
Molinero
Amalia
A
Campbell
Iain L
IL
Palmiter
Richard D
RD
Hidalgo
Juan
J
D000818:Animals; D017209:Apoptosis; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D002540:Cerebral Cortex / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D005615:Freezing; D019922:GAP-43 Protein / Q000378:metabolism; D005786:Gene Expression Regulation; D005911:Gliosis / Q000473:pathology; D008668:Metallothionein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D000090023:Metallothionein 3; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D013601:T-Lymphocytes / Q000473:pathology
D016207:Cytokines; D019922:GAP-43 Protein; D000090023:Metallothionein 3; C000715430:Mt3 protein, mouse; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D008668:Metallothionein