Denervation in the primary olfactory pathway of mice. IV. Biochemical and morphological evidence for neuronal replacement following nerve section.

Unilateral olfactory nerve section was performed in the mouse. Three biochemical markers of the olfactory chemoreceptor neurons: carnosine, carnosine synthetase activity and the olfactory marker protein, were measured in the olfactory bulb and epithelium. Parallel observations were made by light microscopy as well as at the ultrastructural level. The specific biochemical markers decrease rapidly in both bulb and epithelium and reach a minimum by the end of the first week after surgery. They then slowly return to 80% of control values by one month. Carnosinase activity in epithelium was essentially unaffected. These biochemical observations coincide temporally with the onset of degenerative changes seen morphologically, in both the bulb and epithelium. The degenerative changes persist for up to two weeks in the bulb and for about one week in the epithelium. At this time basal cell division and differentiation begins in the epithelium with subsequent regrowth of olfactory axons into the glomerular layer of the olfactory bulb with ther reappearance of olfactory axon terminals. The temporal coincidence of these biochemical and morphological observations suggests they are manifestations of the same process, and is consistent with the idea that the olfactory chemoreceptor neurons are perhaps unique in being able to be replaced from undifferentiated stem cells.