Ontogenic cell death in the nigrostriatal system

摘要: Like most neural systems, dopamine neurons of the substantia nigra undergo apoptotic natural cell death during development. In rodents, this occurs largely postnatally and is biphasic with an initial major peak just after birth a second minor on postnatal day 14. As envisioned by classic neurotrophic theory, event regulated interactions target these neurons, striatum, because developmental lesion results in augmented fewer nigral surviving into adulthood. Until recently, striatal target-derived factors providing support were unknown, but there now growing evidence that glial-cell-line-derived factor (GDNF) serves as physiologic limiting for first phase death. During phase, intrastriatal injection GDNF diminishes neutralizing antibodies augment it. Sustained overexpression striatum throughout development unique double transgenic mouse model increased number However, increase does not persist Therefore, other or mechanisms must play important roles determination mature neurons. Further elucidation will be neuroprotective replacement therapies Parkinson’s disease.