Reduced p75NTR expression delays disease onset only in female mice of a transgenic model of familial amyotrophic lateral sclerosis.
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 p75NTR receptor 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 p75NTR is 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.
D000690:Amyotrophic Lateral Sclerosis / Q000401:mortality / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001253:Astrocytes / Q000473:pathology; D002452:Cell Count; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D005911:Gliosis / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000201:enzymology / Q000473:pathology; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D015996:Survival Rate
D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1