Pathology of the olfactory mucosa: implications for the treatment of olfactory dysfunction.
OBJECTIVE
The pathology of the olfactory mucosa is poorly understood; however, most cases of hyposmia and anosmia appear to be associated with a decline in the number of functioning mature olfactory sensory neurons (OSNs). Under normal conditions, OSNs undergo apoptotic cell death at a baseline rate likely secondary to their exposed location in the nose. Regeneration of mature OSNs from precursors in the epithelium allows the animal to maintain an adequate number of neurons necessary for olfactory sensation. In many cases of olfactory dysfunction, this balance is apparently disturbed, with a net loss of OSNs. The current study will examine normal and diseased olfactory tissue for the presence of data demonstrating that the preferred mechanism of OSN cell death is apoptotic in both health and disease. The potential therapeutic implications will be discussed.


METHODS
Histologic analysis of human and animal olfactory tissue.


METHODS
Normal and diseased human and animal olfactory mucosa were assessed for immunohistochemical evidence of apoptosis.


RESULTS
Increased activity of the apoptotic effector enzyme caspase-3 was demonstrated in diseased olfactory mucosa in comparison with normal controls.


CONCLUSIONS
These results indicate that a common pathway may mediate OSN cell death from a diverse set of pathologic insults including aging, trauma, and sinusitis. Interference with this pathway of cell death is currently the subject of intense pharmacotherapeutic research for the management of stroke and meningitis. These drugs may ultimately prove useful in the treatment of clinical olfactory dysfunction.
Kern
R C
RC
Department of Otolaryngology-Head and Neck Surgery, Northwestern University School of Medicine, 303 E. Chicago Ave. Searle Bldg. 12-561, Chicago, IL 60611, USA.
Conley
D B
DB
Haines
G K
GK
Robinson
A M
AM
D000375:Aging / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009475:Neurons, Afferent / Q000473:pathology; D000857:Olfaction Disorders / Q000188:drug therapy / Q000473:pathology*; D009830:Olfactory Bulb / Q000293:injuries; D009831:Olfactory Mucosa / Q000201:enzymology / Q000473:pathology*; D051381:Rats; D011912:Rats, Inbred ACI; D012852:Sinusitis / Q000473:pathology
C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases