Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Neurobiology of Disease |
| Vol/bind | 9 |
| Udgave nummer | 3 |
| Sider (fra-til) | 319-338 |
| Antal sider | 19 |
| ISSN | 0969-9961 |
| DOI | |
| Status | Udgivet - 2002 |
Bibliografisk note
(c) 2002 Elsevier Science (USA).Adgang til dokumentet
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I: Neurobiology of Disease, Bind 9, Nr. 3, 2002, s. 319-338.
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
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TY - JOUR
T1 - Metallothionein-1+2 deficiency increases brain pathology in transgenic mice with astrocyte-targeted expression of interleukin 6
AU - Giralt, Mercedes
AU - Penkowa, Milena
AU - Hernández, Joaquín
AU - Molinero, Amalia
AU - Carrasco, Javier
AU - Lago, Natalia
AU - Camats, Jordi
AU - Campbell, Iain L
AU - Hidalgo, Juan
N1 - Keywords: Animals; Astrocytes; Brain; Brain Chemistry; Cerebellum; Female; Glial Fibrillary Acidic Protein; Interleukin-6; Male; Metallothionein; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Motor Skills
PY - 2002
Y1 - 2002
N2 - Transgenic expression of IL-6 under the control of the GFAP gene promoter (GFAP-IL6 mice) in the CNS causes significant damage and alters the expression of many genes, including the metallothionein (MT) family, especially in the cerebellum. The crossing of GFAP-IL6 mice with MT-1+2 knock out (MTKO) mice provided evidence that the increased MT-1+2 expression normally observed in the GFAP-IL6 mice is an important mechanism for coping with brain damage. Thus, the GFAP-IL6xMTKO mice showed a decreased body weight gain and an impaired performance in the rota-rod test, as well as a higher upregulation of cytokines such as IL-6, IL-1alpha,beta, and TNFalpha and recruitment and activation of macrophages and T cells throughout the CNS but mainly in the cerebellum. Clear symptoms of increased oxidative stress and apoptotic cell death caused by MT-1+2 deficiency were observed in the GFAP-IL6xMTKO mice. Interestingly, MT-1+2 deficiency also altered the expected frequency of the offspring genotypes, suggesting a role of these proteins during development. Overall, the results suggest that the MT-1+2 proteins are valuable factors against cytokine-induced CNS injury.
AB - Transgenic expression of IL-6 under the control of the GFAP gene promoter (GFAP-IL6 mice) in the CNS causes significant damage and alters the expression of many genes, including the metallothionein (MT) family, especially in the cerebellum. The crossing of GFAP-IL6 mice with MT-1+2 knock out (MTKO) mice provided evidence that the increased MT-1+2 expression normally observed in the GFAP-IL6 mice is an important mechanism for coping with brain damage. Thus, the GFAP-IL6xMTKO mice showed a decreased body weight gain and an impaired performance in the rota-rod test, as well as a higher upregulation of cytokines such as IL-6, IL-1alpha,beta, and TNFalpha and recruitment and activation of macrophages and T cells throughout the CNS but mainly in the cerebellum. Clear symptoms of increased oxidative stress and apoptotic cell death caused by MT-1+2 deficiency were observed in the GFAP-IL6xMTKO mice. Interestingly, MT-1+2 deficiency also altered the expected frequency of the offspring genotypes, suggesting a role of these proteins during development. Overall, the results suggest that the MT-1+2 proteins are valuable factors against cytokine-induced CNS injury.
U2 - 10.1006/nbdi.2002.0480
DO - 10.1006/nbdi.2002.0480
M3 - Journal article
C2 - 11950277
SN - 0969-9961
VL - 9
SP - 319
EP - 338
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 3
ER -