Reduced p75NTRexpression delays disease onset only in female mice of a transgenic model of familial amyotrophic lateral sclerosis

B.M. Küst, N. Brouwer, I.J. Mantingh, H.W.G.M. Boddeke, J.C.V.M. Copray

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35 Citations (Scopus)


hSOD1 (G93A) transgenic mice develop pathological changes similar to those in patients with familial amyotrophic lateral sclerosis (FALS). In particular, the progressive degeneration of motoneurons is charactered in this mouse model. One feature of stressed motoneurons in ALS and the hSOD1 mice is the induction of the p75 neurotrophin receptor, which is thought, under certain circumstances, to be a death-signaling molecule. We have studied disease progression of hSOD1 (G93A) mice in the absence of the p75NTRreceptor and we monitored histological changes in the ventral spinal cord. Whereas female double transgenics showed prolonged survival, this effect was not observed in males. Improved survival in female mice was not correlated with increased motoneuronal survival, but with less astrocytic activation in lumbar ventral spinal cord, as shown by glial fibrillary acidic protein immunohistochemistry. These data suggest that p75NTRis not directly involved in the mechanism leading to motoneuron degeneration. More likely, an indirect process, presumably via regulation of astrocytes, might be responsible for the increased survival responses of female double transgenic mice.
Original languageEnglish
Pages (from-to)100-105
Number of pages6
JournalAmyotrophic lateral sclerosis and other motor neuron disorders
Issue number2
Publication statusPublished - 1-Jun-2003


  • ALS
  • Astrocytes
  • Neurotrophin
  • Sexual dimorphism
  • SOD1
  • copper zinc superoxide dismutase
  • glial fibrillary acidic protein
  • neurotrophin receptor
  • protein p75
  • amyotrophic lateral sclerosis
  • animal experiment
  • animal model
  • animal tissue
  • article
  • astrocyte
  • cell death
  • cell survival
  • controlled study
  • correlation analysis
  • disease course
  • familial disease
  • female
  • histopathology
  • immunohistochemistry
  • male
  • motoneuron
  • mouse
  • nerve cell degeneration
  • nonhuman
  • onset age
  • priority journal
  • protein expression
  • sex difference
  • signal transduction
  • spinal cord
  • transgenic mouse

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