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Soluble TNF receptors partially protect injured motoneurons in the postnatal CNS
Author(s) -
Terrado José,
Monnier Dominique,
Perrelet Daniel,
Vesin Dominique,
Jemelin Stéphane,
Buurman Wim A.,
Mattenberger Louise,
King Béatrice,
Kato Ann C.,
Garcia Irene
Publication year - 2000
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2000.00240.x
Subject(s) - lymphotoxin , axotomy , neuroprotection , receptor , tumor necrosis factor alpha , lymphotoxin beta receptor , biology , spinal cord , in vivo , genetically modified mouse , neuroscience , endocrinology , central nervous system , cytokine , medicine , transgene , immunology , biochemistry , microbiology and biotechnology , gene
There is accumulating evidence that cytokines are involved in the functioning of the brain and the spinal cord. However, it has been controversial whether they exert a neurotoxic or a neuroprotective effect. To address this question in vivo, we have examined the survival of injured motoneurons in a line of transgenic mice that overexpress the soluble form of tumour necrosis factor receptor‐1 (sTNFR1). In these animals, all of the circulating TNF and lymphotoxin‐α are neutralized by the continuous expression of the soluble receptor. Following axotomy of the facial nerve in 7‐day‐old control mice, we observed a loss of approximately 90% of the motoneurons at two weeks survival. In the transgenic mice under the same conditions, the percentage of motoneuron survival was increased two‐fold (515 vs. 224) and varied as a function of the level of the circulating receptor. These results indicate that neutralization of endogenous TNF and lymphotoxin‐α by means of overexpression of the soluble receptor can decrease cell death of injured motoneurons and suggest that these cytokines may play an important role in neuronal degeneration in the CNS following a lesion.