Pathology of the olfactory epithelium: smoking and ethanol exposure.
OBJECTIVE
To investigate the effects of tobacco smoke on the olfactory epithelium. Cigarette smoking has been associated with hyposmia; however, the pathophysiology is poorly understood. The sense of smell is mediated by olfactory sensory neurons (OSNs) exposed to the nasal airway, rendering them vulnerable to environmental injury and death. As a consequence, a baseline level of apoptotic OSN death has been demonstrated even in the absence of obvious disease. Dead OSNs are replaced by the mitosis and maturation of progenitors to maintain sufficient numbers of neurons into adult life. Disruption of this balance has been suggested as a common cause for clinical smell loss. This current study will evaluate the effects of tobacco smoke on the olfactory mucosa, with emphasis on changes in the degree of OSN apoptosis.


METHODS
A rat model was used to assess the olfactory epithelium after exposure to tobacco smoke.


METHODS
Rats were exposed to tobacco smoke alone (for 12 weeks), smoke plus dietary ethanol (for the final 5 weeks), or to neither (control). Immunohistochemical analysis of the olfactory epithelium was performed using an antibody to the active form of caspase-3. Positive staining for this form of the caspase-3 enzyme indicates a cell undergoing apoptotic proteolysis.


RESULTS
Control rats demonstrated a low baseline level of caspase-3 activity in the olfactory epithelium. In contrast, tobacco smoke exposure triggered a dramatic increase in the degree of OSN apoptosis that affected all stages of the neuronal lineage.


CONCLUSIONS
These results support the following hypothesis: smell loss in smokers is triggered by increased OSN death, which eventually overwhelms the regenerative capacity of the epithelium.
Department of Biomedical Sciences, Creighton University, Omaha, NE, USA.
J
J
Vent
A M
AM
Robinson
M J
MJ
Gentry-Nielsen
D B
DB
Conley
R
R
Hallworth
D A
DA
Leopold
R C
RC
Kern
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002452:Cell Count; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D009831:Olfactory Mucosa / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014028:Tobacco Smoke Pollution
D014028:Tobacco Smoke Pollution; D000431:Ethanol; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases