Diverging mechanisms for TNF‐α receptors in normal mouse brains and in functional recovery after injury: From gene to behavior

• DOI: 10.1002/jnr.21126
• Publication Date: 2006-11-28T03:24:37Z
• Authors: Albert Quintana; Amalia Molinero; Sergi Florit; Yasmina Manso; Gemma Comes; Javier Carrasco; Mercedes Giralt; Rehannah Borup; Finn Cilius Nielsen; Iain L. Campbell; Milena Penkowa; Juan Hidalgo
• Keywords: Mice, Knockout; Analysis of Variance; Behavior, Animal; Brain; Recovery of Function; Motor Activity; Receptors, Tumor Necrosis Factor; Mice, Inbred C57BL; Mice; 03 medical and health sciences; 0302 clinical medicine; Gene Expression Regulation; Receptors, Tumor Necrosis Factor, Type I; Brain Injuries; Exploratory Behavior; Animals; Metallothionein; Maze Learning; In Situ Hybridization; Psychomotor Performance; Oligonucleotide Array Sequence Analysis

AbstractCytokines, such as tumour necrosis factor (TNF)‐α and lymphotoxin‐α, 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 ∼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. © 2006 Wiley‐Liss, Inc.