ON THE FORMATION OF NEUROMAS IN THE PRIMARY OLFACTORY PROJECTION

Olfactory axons have been shown to grow aberrantly and form dense coll ections of axons, termed neuromas, in the olfactory epithelium of rats in which the olfactory bulb was ablated. Likewise, in human olfactory mucosa, collections of neurites have been noted in a variety of disea se states, including Alzheimer's disease. We report here an immunohist ochemical and electron microscopic analysis of aberrant axonal growth in the rat olfactory mucosa induced by experimental lesion. In particu lar, we have used the monoclonal antibody 2G12, which binds to the pho sphorylated form of GAP-43, as an extremely sensitive marker for neuro matous axons, because it does not label neuronal cell bodies. In unila terally bulbectomized rats, neuromas form in posterior olfactory epith elium on the operated side. Several lines of evidence, including seria l section reconstruction, indicate that olfactory axons are induced to grow back into the epithelium at a distance from their point of origi n as a consequence of bulbectomy, and are accompanied by glial cells f rom the olfactory nerve. Avulsion of a part of the olfactory nerve has similar effects as destruction of the olfactory bulb. Intraepithelial neuromas also develop in the olfactory mucosa of rats simultaneously exposed to methyl bromide gas and injected with 3-methyl indole; this treatment severely damages the olfactory epithelium directly. Exposure to methyl bromide alone causes milder damage, and the neuromas that f orm are transient. The evidence indicates that neuromas form after the epithelium is directly damaged because axons are trapped in the epith elium. Both of the mechanisms identified here should be taken into acc ount when considering the findings in the human olfactory mucosa. (C) 1994 Wiley-Liss, Inc.