APOPTOSIS IN THE NEURONAL LINEAGE OF THE MOUSE OLFACTORY EPITHELIUM -REGULATION IN-VIVO AND IN-VITRO

The olfactory epithelium (OE) of the mouse provides a unique system fo r understanding how cell birth and cell death interact to regulate neu ron number during development and regeneration. We have examined cell death in the OE in normal adult mice; in adult mice subjected to unila teral olfactory bulbectomy (surgical removal of one olfactory bulb, th e synaptic target of olfactory receptor neurons (ORNs) of the OE); and in primary cell cultures derived from embryonic mouse OE. In vivo, ce lls at all stages in the neuronal lineage-proliferating neuronal precu rsors, immature ORNs, and mature ORNs-displayed signs of apoptotic cel l death; nonneuronal cells did not. Bulbectomy dramatically increased the number of apoptotic cells in the OE on the bulbectomized side. Sho rtly following bulbectomy, increased cell death involved neuronal cell s of all stages. Later, cell death remained persistently elevated, but this was due to increased apoptosis by mature ORNs alone. In vitro, a poptotic death of both ORNs and their precursors could be inhibited by agents that prevent apoptosis in other cells: aurintricarboxylic acid (ATA), a membrane-permeant analog of cyclic AMP (CPT-cAMP), and certa in members of the neurotrophin family of growth factors (brain-derived neurotrophic factor, neurotrophin 3, and neurotrophin 5), although no neurotrophin was as effective at promoting survival as ATA or CPT-cAM P. Consistent with observed effects of neurotrophins, immunohistochemi stry localized the neurotrophin receptors trkB and trkC to fractions o f ORNs scattered throughout neonatal OE. These results suggest that ap optosis may regulate neuronal number in the OE at multiple stages in t he neuronal lineage and that multiple factors-potentially including ce rtain neurotrophins-may be involved in this process. (C) 1995 Academic Press, Inc.