Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Journal of Neuroscience Research |
| Vol/bind | 85 |
| Udgave nummer | 12 |
| Sider (fra-til) | 2668-85 |
| Antal sider | 17 |
| ISSN | 0360-4012 |
| DOI | |
| Status | Udgivet - 2007 |
Bibliografisk note
(c) 2007 Wiley-Liss, Inc.Adgang til dokumentet
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I: Journal of Neuroscience Research, Bind 85, Nr. 12, 2007, s. 2668-85.
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
}
TY - JOUR
T1 - Diverging mechanisms for TNF-alpha receptors in normal mouse brains and in functional recovery after injury: From gene to behavior
AU - Quintana, Albert
AU - Molinero, Amalia
AU - Florit, Sergi
AU - Manso, Yasmina
AU - Comes, Gemma
AU - Carrasco, Javier
AU - Giralt, Mercedes
AU - Borup, Rehannah
AU - Nielsen, Finn Cilius
AU - Campbell, Iain L
AU - Penkowa, Milena
AU - Hidalgo, Juan
N1 - Keywords: Analysis of Variance; Animals; Behavior, Animal; Brain; Brain Injuries; Exploratory Behavior; Gene Expression Regulation; In Situ Hybridization; Maze Learning; Metallothionein; Mice; Mice, Inbred C57BL; Mice, Knockout; Motor Activity; Oligonucleotide Array Sequence Analysis; Psychomotor Performance; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type I; Recovery of Function
PY - 2007
Y1 - 2007
N2 - Cytokines, such as tumour necrosis factor (TNF)-alpha and lymphotoxin-alpha, have been described widely to play important roles in the brain in physiologic conditions and after traumatic injury. However, the exact mechanisms involved in their function have not been fully elucidated. We give some insight on their role by using animals lacking either Type 1 receptor (TNFR1KO) or Type 2 (TNFR2KO) and their controls (C57Bl/6). Both TNFR1KO and to a greater extent TNFR2KO mice showed increased exploration/activity neurobehavioral traits in the hole board test, such as rearings, head dippings, and ambulations, compared with wild-type mice, suggesting an inhibitory role of TNFR1/TNFR2 signaling. In contrast, no significant differences were observed in the elevated plus maze test, ruling out a major role of these receptors in the control of anxiety. We next evaluated the response to a freeze injury to the somatosensorial cortex. The effect of the cryolesion on motor function was evaluated with the horizontal ladder beam test, and the results showed that both TNFR1KO and TNFR2KO mice made fewer errors, suggesting a detrimental role for TNFR1/TNFR2 signaling for coping with brain damage. Expression of approximately 22600 genes was analyzed using an Affymetrix chip (MOE430A) at 0 (unlesioned), 1, or 4 days post-lesion in the three strains. The results show a unique and major role of both TNF receptors on the pattern of gene expression elicited by the injury but also in normal conditions, and suggest that blocking of TNFR1/TNFR2 receptors may be beneficial after a traumatic brain injury.
AB - Cytokines, such as tumour necrosis factor (TNF)-alpha and lymphotoxin-alpha, have been described widely to play important roles in the brain in physiologic conditions and after traumatic injury. However, the exact mechanisms involved in their function have not been fully elucidated. We give some insight on their role by using animals lacking either Type 1 receptor (TNFR1KO) or Type 2 (TNFR2KO) and their controls (C57Bl/6). Both TNFR1KO and to a greater extent TNFR2KO mice showed increased exploration/activity neurobehavioral traits in the hole board test, such as rearings, head dippings, and ambulations, compared with wild-type mice, suggesting an inhibitory role of TNFR1/TNFR2 signaling. In contrast, no significant differences were observed in the elevated plus maze test, ruling out a major role of these receptors in the control of anxiety. We next evaluated the response to a freeze injury to the somatosensorial cortex. The effect of the cryolesion on motor function was evaluated with the horizontal ladder beam test, and the results showed that both TNFR1KO and TNFR2KO mice made fewer errors, suggesting a detrimental role for TNFR1/TNFR2 signaling for coping with brain damage. Expression of approximately 22600 genes was analyzed using an Affymetrix chip (MOE430A) at 0 (unlesioned), 1, or 4 days post-lesion in the three strains. The results show a unique and major role of both TNF receptors on the pattern of gene expression elicited by the injury but also in normal conditions, and suggest that blocking of TNFR1/TNFR2 receptors may be beneficial after a traumatic brain injury.
U2 - 10.1002/jnr.21126
DO - 10.1002/jnr.21126
M3 - Journal article
C2 - 17131423
SN - 0360-4012
VL - 85
SP - 2668
EP - 2685
JO - Journal of Neuroscience Research
JF - Journal of Neuroscience Research
IS - 12
ER -