The induction of multiple cell cycle events precedes target-related neuronal death

作者: Karl Herrup , Jonathan C. Busser

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摘要: Unexpected nerve cell death has been reported in several experimental situations where neurons have forced to re-enter the cycle after leaving ventricular zone and entering G0, non-mitotic stage. To determine whether an association between unscheduled cycling might be found conjunction with any naturally occurring developmental events, we examined target-related two neuronal populations, granule cells of cerebellar cortex inferior olive. Both these populations a demonstrated dependency on their synaptic target, Purkinje cell. Two mouse neurological mutants, staggerer (sg/sg) lurcher (+/Lc), are characterized by intrinsic deficiencies and, both substantial numbers olive die due absence trophic support from main postsynaptic target. We report here that levels three independent markers--cyclin D, proliferating nuclear antigen bromodeoxyuridine incorporation--are elevated before they die. Although during similar period, no compelling evidence for involvement this instance pre-programmed could found. While application TUNEL technique (in situ terminal transferase end-labeling fragmented DNA) failed label dying either mutant, light electron microscopic observations consistent interpretation is apoptotic nature. Together, data indicate developing central nervous system associated mechanism involves apparent loss control.

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