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.