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Scientific article
English

Soluble TNF receptors partially protect injured motoneurons in the postnatal CNS

Published inEuropean journal of neuroscience, vol. 12, no. 9, p. 3443-3447
Publication date2000
Abstract

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-alpha 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-alpha 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.

Keywords
  • Age Factors
  • Animals
  • Axotomy
  • Cell Survival/physiology
  • Facial Nerve/chemistry/physiology
  • Lymphotoxin-alpha/analysis
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Motor Neurons/*cytology/*physiology
  • Nerve Degeneration/physiopathology
  • Receptors, Tumor Necrosis Factor/*physiology
  • Solubility
  • Spinal Cord/*cytology
  • Transgenes/physiology
  • Tumor Necrosis Factor-alpha/analysis
Affiliation Not a UNIGE publication
Citation (ISO format)
TERRADO, J. et al. Soluble TNF receptors partially protect injured motoneurons in the postnatal CNS. In: European journal of neuroscience, 2000, vol. 12, n° 9, p. 3443–3447. doi: 10.1046/j.1460-9568.2000.00240.x
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ISSN of the journal0953-816X
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