Induction of neurofibrillary tangles in cultured mouse neurons by maytanprine.
Neurofibrillary (neurofilament) tangles were induced in cultured neurons of newborn mouse dorsal root ganglia by exposure to maytanprine, an anti-microtubule drug. By 12-24 h of treatment, small short neurofilament bundles were found in the neuronal perikarya and proximal portions of the neurites. By 48-72 h of treatment, small neurofilament bundles were assembled into larger masses, and after 72 h and onward several neurofilament bundles coalesced into single large distinctive perinuclear rings in the neuronal perikarya. A histometric analysis of maytanprine treated axons demonstrated that the density of microtubules decreased rapidly, while that of neurofilaments decreased more slowly. As a result of microtubule depolymerization by maytanprine treatment, neurofilaments change their distribution pattern in neuronal perikarya and subsequently form tangles.
D000818:Animals; D000831:Animals, Newborn; D046508:Culture Techniques; D003599:Cytoskeleton / Q000187:drug effects; D005727:Ganglia, Spinal; D008453:Maytansine / Q000031:analogs & derivatives / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D008870:Microtubules / Q000187:drug effects; D009454:Neurofibrils / Q000187:drug effects*; D010078:Oxazines / Q000494:pharmacology*
D010078:Oxazines; D008453:Maytansine; C033351:maytanprine