Prion protein (PrP ^c ) positively regulates neural precursor proliferation during developmental and adult mammalian neurogenesis

Abstract

neural development ͉ neural precursor ͉ subventricular zone ͉ dentate gyrus

New insights into cellular prion protein (PrPc) functions: The “ying and yang” of a relevant protein

“…In the adult, PrP c is not expressed by proliferating cells in the subventricular zone of the lateral ventricle (Steele et al, 2006). (Steele et al, 2006). Surprisingly, previous in vitro studies showed that PrP c -deficient neural cell lines derived from embryonic hippocampus display higher proliferative rates than WT cells in culture (Kim et al, 2005).…”

“…In mice, PrP c expression starts during development around embryonic day E8,5-9 in postmitotic neurons (Miele et al, 2003) and around day E13,5-16,5 in specific nonneuronal populations (Manson et al, 1992). In the adult, PrP c is not expressed by proliferating cells in the subventricular zone of the lateral ventricle (Steele et al, 2006). (Steele et al, 2006).…”

“…These data indicate that the structural effects of neural PrP c during synapse formation and stabilization may occur in intrinsic or extrinsic ways. Intrinsic Prnp expression is developmentally regulated (Miele et al, 2003) and takes place postnatally in neural tissue (Steele et al, 2006), especially during the fate restriction of multipotential cells towards the neural lineage (Mouillet-Richard et al, 1999), stages characterized by neuronal polarization and synapse formation. Conversely, extracellular PrP c may act via specific receptors in neighboring neurons to promote synapse formation and neuronal maturation (Graner et al, 2000;Kanaani et al, 2005).…”

Heat shock factor 1 regulates lifespan as distinct from disease onset in prion disease

“…Mice were obtained on a mixed 129SvEv ϫ BALB/c strain background and were crossed once to C57BL/6J and maintained by intercrossing mice heterozygous for the HSF1 deletion allele. The titering of the infectivity of samples used Tga20 recipient mice that had been backcrossed to C57BL/6J for 5-6 generations and bred onto a WT PrP genome (55).…”

Les prions

“…Sa fonction semble liée à l'activité synaptique, l'adhé-rence cellulaire et la poussée neuritique en association avec d'autres molécules (LRP, Laminine, N-CAM) [40][41][42]. Récemment, il a même été montré que la PrP régulerait la prolifération des précurseurs neuraux durant le développement et lors de la neurogenèse adulte [43] ainsi que la prolifération des cellules souches hématopoïétiques [44]. Aussi, la modification des fonctions physiologiques de la PrP C dans les cellules neuronales au cours de l'infection pourrait expliquer les altérations neuronales observées [56].…”