NR AVNE
AU Coulpier,M.; Messiaen,S.; Boucreaux,D.; Eloit,M.
TI Axotomy-induced motoneuron death is delayed in mice overexpressing PrPc
QU Neuroscience 2006 Sep 15; 141(4): 1827-34
PT comparative study; journal article; research support, non-u.s. gov't
AB The normal function of the cellular prion protein, PrPc, remains largely unknown. Recently, PrPc has been implicated in the regulation of neuronal survival and was shown to confer neuroprotection in the brain. To pursue investigation of the role of PrPc in the CNS, we used the facial nerve section, a well-established experimental model of motoneuronal stress. Nerve sections were performed in 2- and 7-day-old newborn mice and in 2 month-old adult mice expressing different levels of PrPc. We observed no differences in motoneuronal death triggered by facial nerve section between Prnp-/- and wild-type mice, whether in neonatal or adult mice. By contrast, overexpression of PrPc in Tga20 newborn mice was correlated with a better survival of motoneurons in the few days following axotomy. The protection was, however transient since motoneuron number in lesioned facial nuclei of Tga20 mice became identical to that of wild-type mice 7 days and 14 days following the lesion when performed in 2- and 7-day-old mice respectively. In Tga20 adult mice, no protection was observed 2 months after the lesion, a time with a significant degree of motoneuron death in adult control mice. These results, while providing further evidence that PrPc is endowed with neuroprotective capacity in vivo, also suggest that PrPc does not play a physiological role in the regulation of motoneuronal survival.
MH Age Factors; Analysis of Variance; Animals; Animals, Newborn; Axotomy/*adverse effects/methods; Blotting, Western/methods; Caspase 3/metabolism; Cell Count/methods; Cell Death/physiology; Facial Nerve Injuries/etiology/genetics/*pathology; Gene Expression Regulation, Developmental/*physiology; Immunohistochemistry/methods; Mice; Mice, Inbred C57BL; Mice, Transgenic; Motor Neurons/*physiology; Prions/genetics/*metabolism; Time Factors
AD UMR Virologie 1161 Institut National de la Recherche Agronomique-Agence Francaise de Securite Sanitaire des Aliments-Ecole Nationale Veterinaire d'Alfort, Ecole Nationale Veterinaire d'Alfort, 94704 Maisons-Alfort, France. mcoulpier@vet-alfort.fr
SP englisch
PO USA