title: Neuronal maturation-associated resistance of neurite degeneration caused by trophic factor deprivation or microtubule-disrupting agents.
abstract: Neurite (axon and dendrite) degeneration requires self-destructive programs independent of cell death programs to segregate neurite degeneration from cell soma demise. We have here addressed the question of whether neuritic degeneration is delayed or occurs normally under conditions in which sympathetic neurons acquire resistance to somal apoptosis upon maturation. For this purpose, we have examined both beading formation and fragmentation, two hall-marks of neurite degeneration, caused by three experimental paradigms including NGF deprivation, treatment with microtubule-disrupting agents, and in vitro Wallerian degeneration. Sympathetic neurons from 1-day-old mice or newborn rats were grown for 5-6 days (young) or 3 weeks (mature). Mature neurons acquired resistance to apoptosis caused by colchicine as well as NGF withdrawal. Neither cytochrome c release nor DNA fragmentation occurred. Both beading formation and subsequent fragmentation were delayed in mature neurons following NGF deprivation, treatment with colchicine, or in vitro Wallerian degeneration. Neuritic ATP levels of young ganglia decreased rapidly, while those of mature ganglia did so slowly during degeneration, although the basal levels of neuritic ATP of both ganglia were similar. Notably, mature neurites were resistant to fragmentation caused by NGF deprivation and capable of growing again after replenishment of NGF. This development of resistance to neurite degeneration in mature neurons may be thought as an important protective mechanism for the maintenance of the adult nervous system.
authors.affiliation: Molecular Neurobiology Laboratory, Division of Life Science, Hokkaido University, Graduate School of Life Science, North Ward N10W8, Science Building #5, Room 9512, Sapporo 060-0810, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Kawataki
authors.forename: Kaori
authors.initials: K
authors.lastname: Osafune
authors.forename: Mari
authors.initials: M
authors.lastname: Suzuki
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Koike
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000502:physiology; D003078:Colchicine / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D005456:Fluorescent Dyes; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D008870:Microtubules / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure; D009410:Nerve Degeneration / Q000473:pathology*; D020932:Nerve Growth Factor / Q000502:physiology*; D016501:Neurites / Q000473:pathology* / Q000648:ultrastructure; D009474:Neurons / Q000473:pathology* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects; D014855:Wallerian Degeneration / Q000473:pathology
chemical_list: D005456:Fluorescent Dyes; D000255:Adenosine Triphosphate; D020932:Nerve Growth Factor; D003078:Colchicine