Unusual neurofibrillary accumulations induced by beta,beta'-iminodipropionitrile (IDPN)

Beta,beta'-iminodipropionitrile (IDPN) is a synthetic compound known to induce massive focal accumulations of neurofilaments almost exclusively in the proximal segments of motor and sensory axons. The present paper deals with a cat intoxicated with IDPN for five weeks. Swellings filled with skeins of maloriented neurofilaments were observed in the initial (non-myelinated) segment of intraparenchymal spinal axons in addition to the swellings consistently located in the first internodes. Filamentous masses in the initial segment were in some cases intermingled with focal accumulations of mitochondria and smooth vesicles to give the proximal axon the classical appearance of 'spheroid'. In some motoneurons, clumps of neurofilaments occupied the axon hillock and extended well into the perikaryon and some dendritic stems, making the borderlines between cell body and processes undistinguishable. Cytoplasmic organelles were displaced and rearranged in the presence of somal neurofibrillary changes. In a few neurons, regardless of the presence of swellings in the axon initial segment, signs of central chromatolysis were noticed, in the form of nuclear caps of Nissl substance and eccentricity of the nucleus. These findings are discussed with reference to other neurotoxic models of neurofibrillary pathology and the immunochemical differences recently detected between neurofilaments in perikarya, dendrites and axons.