Cellular responses to a wide variety of physiological stresses (including elevated both temperature, viral infections, Ph changes, and surgical and impact trauma) include specifically enhanced expression of several families of proteins, the stress or heat shock proteins (hsp's, so named because of their early association with responses to heat stress). Many conditions known to evoke the stress protein response are conditions which result in formation of abnormal or denatured proteins. The stress response may function to protect cells from injurious accumulation of such abnormal proteins. The long range objective of these studies is to understand the role of stress proteins in the olfactory epithelium (OE). The OE is unique among vertebrate neural tissue in its continuous genesis and replacement of sensory neurons and in the direct contact of these neurons with the external environment which renders them especially vulnerable to stressing environmental events. Preliminary data suggest that stress protein responses to olfactory bulbectomy may reflect these unique properties and that control of the stress protein responses may be different from that seen elsewhere in the nervous system. The study proposed herein will examine stress responses of cells in the rat OE using monoclonal antibodies (Mabs) to two stress proteins groups the hsp70 family and ubiquitin. The study seeks to answer three questions: 1. Is sensory neuron hsp70 expression an age-related phenomenon? 2. What is the time course of OE hsp's and ubiquitin expression following olfactory bulbectomy: 3 Will nonsurgical stress include the stress response oOE sensory neurons? To answer these questions the proposed research will examine the immunoreactivity of these Mabs immunohistochemically in normal OE and OE subjected to a variety of surgical, environmental, and physiological stresses (olfactory bulbectomy and bulbectomy-induced synaptic target deprivation, olfactory nerve axotomy neonatal naris closure, decreased O2, and hyperthermia). Tritiated thymidine autoradiography will be used in conjunction with the immunohistochemistry in the analyses of OE sensory neuron age at the onset of hsp70 expression. In addition, in site hybridization studies will examine hsp70 and ubiquitin MRNA expression and permit comparison of message and protein expression in response to bulbectomy.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Small Research Grants (R03)
Project #
1R03DC001593-01
Application #
3424642
Study Section
Special Emphasis Panel (SRC (03))
Project Start
1992-04-01
Project End
1994-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
1
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Type
Schools of Arts and Sciences
DUNS #
City
Evanston
State
IL
Country
United States
Zip Code
60201