Role of metallothionein-III following central nervous system damage

• Published in: Neurobiology of disease Vol. 13; no. 1; pp. 22 - 36
• Main Authors: Carrasco, Javier, Penkowa, Milena, Giralt, Mercedes, Camats, Jordi, Molinero, Amalia, Campbell, Iain L., Palmiter, Richard D., Hidalgo, Juan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-06-2003; Elsevier
• Subjects: Animals; Apoptosis; Brain Injuries - metabolism; Brain Injuries - pathology; Cell Count; Cerebral Cortex - injuries; Cerebral Cortex - metabolism; Cerebral Cortex - pathology; Cytokines - biosynthesis; Freezing; GAP-43 Protein - metabolism; Gene Expression Regulation; Gliosis - pathology; Metallothionein - deficiency; Metallothionein - genetics; Metallothionein - metabolism; Mice; Mice, Inbred Strains; Mice, Knockout; Nerve Growth Factors - metabolism; Nerve Tissue Proteins - deficiency; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Oxidative Stress; T-Lymphocytes - pathology
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/S0969-9961(03)00015-9

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.