Neuronal argyrophilia and phosphorylated neurofilament accumulation secondary to deafferentation

This work tests the hypothesis that deafferentation caused by experimental brain lesions leads to the appearance of perikaryal argyrophilia and the accumulation of phosphorylated cytoskeletal proteins which are potential precursors for neurofibrillary tangle formation. Destructive lesions of the ventral tegmental area, the septum of the medial forebrain and the entorhinal cortex, when combined with systemic administration of a D-1 dopamine receptor antagonist, produced transsynaptic changes in neurons of the hippocampal formation in the midbrain. Abnormally phosphorylated neurofilament protein was demonstrated immunohistochemically in the cytoplasm of mesencephalic pyramidal neurons, particularly in the red nucleus. These same neurons also developed cytoplasmic argyrophilia in Bielschowsky histologic preparations. Although distinct neurofibrillary tangles were not produced with this paradigm, both the protein immunoreactivity and argyrophilia were arranged in cytoplasmic linear arrays. The structural changes induced in this experimental model may be an important preliminary stage for neurofibrillary tangle formation.