Neurotrophin-3 enhances neurite outgrowth in cultured hippocampal pyramidal neurons.
Low density dissociated cultures of embryonic rat hippocampal cells were used to study the effects of neurotrophin-3 (NT-3) on neuronal morphogenesis. The results obtained indicate that NT-3 enhances neurite outgrowth and branching; this is a dose-dependent effect, detected in approximately 50% of the neurons, and prevented by K-252a, an inhibitor of the trk family of receptor protein kinases. NT-3 also accelerates the development of neuronal polarity, a phenomenon preceded by a dramatic accumulation of bundles of looped microtubules within axonal growth cones; these microtubule bundles contain tyrosinated, detyrosinated, and acetylated alpha-tubulin. Taken collectively, our data suggest that even though the basic shape of hippocampal neurons may be endogenously determined, critical aspects of their morphological development may be modulated by trophic factors such as NT-3. In addition, our observations suggest that at least some of the neuritogenic effects of NT-3 involve a stimulation of microtubule assembly and/or transport.
Instituto Mercedes y Martín Ferreyra, Córdoba, Argentina.
G
G
Morfini
M C
MC
DiTella
F
F
Feiguin
N
N
Carri
A
A
Cáceres
D000107:Acetylation; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000648:ultrastructure; D016466:CHO Cells; D002227:Carbazoles / Q000494:pharmacology; D016764:Cell Polarity / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000196:embryology; D026121:Indole Alkaloids; D008870:Microtubules / Q000187:drug effects / Q000648:ultrastructure; D009024:Morphogenesis / Q000187:drug effects; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects*; D020933:Neurotrophin 3; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D017966:Pyramidal Cells / Q000187:drug effects* / Q000648:ultrastructure; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D013268:Stimulation, Chemical; D014404:Tubulin / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D002227:Carbazoles; D020934:Ciliary Neurotrophic Factor; D026121:Indole Alkaloids; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3; D011994:Recombinant Proteins; D014404:Tubulin; D014443:Tyrosine; C049985:staurosporine aglycone