3-Nitrotyrosine immunoreactivity in olfactory receptor neurons of patients with Alzheimer’s disease: implications for impaired odor sensitivity

Expression of a calcium-binding protein, spot 35 protein (S-3S, calbindin-D28k), was investigated immunohistochemically in the human olfactory mucosa of patients who ranged in age from 16 weeks of fetal development to 98 years old, including some with Alzheimer's disease (AD). S-35 immunoreactivity was observed clearly in olfactory receptor neurons (ORNs) and olfactory nerve bundles that were identified previously with antibodies to olfactory marker protein (OMP) and neuron-specific enolase (NSE). Throughout all ages, the mean number of ORNs immunoreactive for OMP did not change significantly, whereas the mean number of NSE- and S-35-immunoreactive ORNs declined markedly in the postnatal infant, young, and old patients when compared with that of the prenatal fetuses. S-35-immunoreactive ORNs decreased significantly in AD patients when compared with AD control patients. These results indicate that ORNs in humans express S-35 and that there is an age-related trend in the expression of S-35. Furthermore, the marked decrease of S-35 expression in ORNs of AD patients suggests that cell excitability associated with calcium ions and cell protective function against overload of intracellular calcium ions decline in these patients.

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Increased Density of Olfactory Receptor Neurons Immunoreactive for Apolipoprotein E in Patients with Alzheimer's Disease

Annals of Otology Rhinology & Laryngology ◽

10.1177/000348949810700511 ◽

1998 ◽

Vol 107 (5) ◽

pp. 421-426 ◽

Cited By ~ 14

Author(s):

Masuo Yamagishi ◽

Shigeru Takami ◽

Marilyn L. Getchell ◽

Thomas V. Getchell

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Apolipoprotein E ◽

Olfactory Receptor ◽

Olfactory Receptor Neurons ◽

Elderly Subjects ◽

Double Labeling ◽

Pgp 9.5 ◽

Receptor Neurons ◽

The Mean

Immunolocalization of apolipoprotein E (apoE) was investigated in human olfactory mucosa in which olfactory receptor neurons (ORNs) were identified with antiserum to protein gene product (PGP) 9.5. Tissue was obtained at autopsy from 10 nondemented middle-aged or elderly subjects and 9 patients with Alzheimer's disease (AD). Double-labeling immunofluorescence established that apoE immunoreactivity was colocalized in a subpopulation of PGP 9.5-immunoreactive ORNs. The mean number of apoE-immunoreactive ORNs per unit epithelial length in AD patients was about 3.5 times greater than that in nondemented patients, although the mean number of PGP 9.5-immunoreactive ORNs was similar. The apoE-immunopositive Schwann cells in olfactory nerve bundles were the probable source of apoE in the ORNs. The increased numbers of apoE-immunoreactive ORNs in AD patients compared to nondemented subjects demonstrates another manifestation of AD-related neuropathology, in addition to cytoskeletal changes, β-amyloid deposition, and changes in immunoreactivity for other neuroproteins, that parallels changes in neurons in the AD brain.

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Human Olfactory Receptor Neurons Express Heat Shock Protein 70: Age-Related Trends

Annals of Otology Rhinology & Laryngology ◽

10.1177/000348949510400108 ◽

1995 ◽

Vol 104 (1) ◽

pp. 47-56 ◽

Cited By ~ 27

Author(s):

Thomas V. Getchell ◽

N. S. Rama Krishna ◽

D. Larry Sparks ◽

Nimrat Dhooper ◽

Marilyn L. Getchell

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Heat Shock ◽

Heat Shock Protein ◽

Olfactory Receptor ◽

Olfactory Receptor Neurons ◽

Hsp 70 ◽

Sustentacular Cells ◽

Age Related ◽

Receptor Neurons

Immunocytochemical methods were used to investigate the cellular distribution and age-related trends in the expression of constitutive and/or inducible forms of heat shock protein (hsp) 70 in the human nasal mucosa of 22 subjects who ranged in age from 16 weeks prenatal to 90 years, including 3 subjects with Alzheimer's disease. The olfactory mucosa was characterized by the presence of olfactory marker protein—immunoreactive olfactory receptor neurons. The hsp 70 immunoreactivity was localized in olfactory receptor neurons and the supranuclear region of sustentacular cells in the olfactory epithelium, and in the acinar cells of the Bowman's glands in the lamina propria. A systematic age-related decrement in the expression of hsp 70 immunoreactivity was observed in the olfactory receptor neurons. This trend was not apparent in sustentacular cells and Bowman's glands. A marked decrement in hsp 70 immunoreactivity was also noted in the olfactory receptor neurons of subjects with Alzheimer's disease when compared to age-matched controls. These results suggest that the age-dependent decrease in hsp 70 in olfactory receptor neurons of older subjects and those with Alzheimer's disease may be attributable to their greater susceptibility to stress.

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Odor sensitivity of cultured lobster olfactory receptor neurons is not dependent on process formation.

Journal of Experimental Biology ◽

10.1242/jeb.174.1.215 ◽

1993 ◽

Vol 174 (1) ◽

pp. 215-233 ◽

Cited By ~ 3

Author(s):

D A Fadool ◽

W C Michel ◽

B W Ache

Keyword(s):

Voltage Clamp ◽

Olfactory Receptor ◽

Cell Voltage ◽

Response Spectra ◽

Olfactory Receptor Neurons ◽

Process Formation ◽

Receptor Neurons ◽

Dual Polarity ◽

Odor Sensitivity

Cultured lobster olfactory receptor neurons (ORNs) were surveyed for their odor sensitivity with whole-cell, voltage-clamp recording. The nature of the adequate stimuli, the degree of tuning (response spectra) of the cells, the threshold of sensitivity and the dual polarity of the odor-evoked currents are consistent with chemosensitivity in the cultured ORNs being olfactory. The ability of odors to evoke currents in cultured ORNs that lack processes suggests that lobster ORNs can be induced in vitro to insert all the elements of the transduction cascade in the soma, including those that might normally be confined to processes. This should greatly facilitate analysis of olfactory transduction in these cells.

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