Previous studies showed that uptake of the lectin conjugate, wheat germ agglutinin-horseradish peroxidase (WGA-HRP) by olfactory receptor cells results in a thinning of the olfactory epithelium (OE) and increased turnover of globose basal cells. To ascertain the cell-type lost as well as the time course and mechanism of the loss, the current study measured changes in the number of dendritic knobs, olfactory marker protein (OMP) expression and assessed TUNEL labeling as an indicator of apoptosis. Electron microscopic analysis of the number of dendritic knobs showed that the largest reduction occurred at 1 week after intranasal irrigation with WGA-HRP. This data in conjunction with decreased OMP staining provided evidence for a loss of mature receptor neurons. TUNEL labeling, especially in more superficial aspects of the OE, peaked at 18 hr after WGA-HRP application suggesting that the lectin-conjugate produced a rapid induction of apoptotic cell death that was complete by 3 days. Measurement of tyrosine hydroxylase (TH) activity in the olfactory bulb, a sensitive measure of deafferentation, showed that innervation reached a nadir at about 1 week and that reinnervation was complete by 4 weeks. These findings demonstrate that internalization of WGA-HRP by some receptor cells results in their death by apoptosis and a subsequent deafferentation of the olfactory bulb.
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