Induction of neurofibrillary tangles in cultured mouse neurons by maytanprine

Abstract

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.