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

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

doi:10.1002/jnr.21126

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

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

21 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Journal of Neuroscience Research
Volume	85
Issue number	12
Pages (from-to)	2668-85
Number of pages	17
ISSN	0360-4012
DOIs	https://doi.org/10.1002/jnr.21126
Publication status	Published - 2007

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Quintana, A., Molinero, A., Florit, S., Manso, Y., Comes, G., Carrasco, J., Giralt, M., Borup, R., Nielsen, F. C., Campbell, I. L., Penkowa, M., & Hidalgo, J. (2007). Diverging mechanisms for TNF-alpha receptors in normal mouse brains and in functional recovery after injury: From gene to behavior. Journal of Neuroscience Research, 85(12), 2668-85. https://doi.org/10.1002/jnr.21126

Quintana, A, Molinero, A, Florit, S, Manso, Y, Comes, G, Carrasco, J, Giralt, M, Borup, R, Nielsen, FC, Campbell, IL, Penkowa, M & Hidalgo, J 2007, 'Diverging mechanisms for TNF-alpha receptors in normal mouse brains and in functional recovery after injury: From gene to behavior', Journal of Neuroscience Research, vol. 85, no. 12, pp. 2668-85. https://doi.org/10.1002/jnr.21126

@article{bd299e60832a11de8bc9000ea68e967b,

title = "Diverging mechanisms for TNF-alpha receptors in normal mouse brains and in functional recovery after injury: From gene to behavior",

abstract = "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.",

author = "Albert Quintana and Amalia Molinero and Sergi Florit and Yasmina Manso and Gemma Comes and Javier Carrasco and Mercedes Giralt and Rehannah Borup and Nielsen, {Finn Cilius} and Campbell, {Iain L} and Milena Penkowa and Juan Hidalgo",

note = "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",

year = "2007",

doi = "10.1002/jnr.21126",

language = "English",

volume = "85",

pages = "2668--85",

journal = "Journal of Neuroscience Research",

issn = "0360-4012",

publisher = "JohnWiley & Sons, Inc.",

number = "12",

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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 -

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

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