The ultimate purpose of this proposal is to study the fundamental molecular mechanism of aging brain and neurodegenerative disorders. The olfactory system will be used as a model system of aging because 1) the olfactory system shows changes in aging and neurodegenerative disorders such as Alzheimer's diseases; 2) it has ideal anatomic segregation of afferent inputs for detailed anatomical work; and 3) the recycling nature of its peripheral afferent receptor cells makes the study of neuronal interactions quite feasible. Aging rat and mouse brain will be studied to investigate the changes in neurotransmitter levels and transmitter synthesizing enzyme activities, correlating with previously noted morphological changes in the olfactory system. If changes in neurotransmitter phenotypes are noted, further characterization of the regulation of neurotransmitter gene expression will be undertaken by immunotitration for the amount of enzyme protein molecules, Northern and dot blot analyses for quantitation of corresponding mRNA levels, and in vitro transcription assay, if the changes are sufficiently large. Afferent regualtion of neurtransmitter phenotype in the olfactory cells will also be studied at the level of gene expression and its change with aging will be investigated. This will be the first attempt to study the gene expression in aging brain at the fundamental level by use of specific probes. The immediate focus of the proposal preceding the above project will be the basic science training period. The candidate will acquire basic metholology and understanding of biochemcial techniques, molecular biological principles, and modern anatomic methodologies through on-going laboratory projects in the sponsor's laboratory. The development of independent research program will allow the candidate to intergrate it with his clinical training in neurodegenerative disorders of aging.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Physician Scientist Award (K11)
Project #
7K11AG000406-06
Application #
3084923
Study Section
Aging Review Committee (AGE)
Project Start
1992-09-11
Project End
1993-07-31
Budget Start
1992-09-11
Budget End
1993-07-31
Support Year
6
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Chicago
Department
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637
Kang, U J; Park, D H; Wessel, T et al. (1992) Dopa-decarboxylation in the striata of rats with unilateral substantia nigra lesions. Neurosci Lett 147:53-7
Park, D H; Kang, U J; Moskowitz, C B et al. (1990) Dopamine beta-hydroxylase activity in cerebrospinal fluid of idiopathic torsion dystonia. Neurology 40:1626-8
Kang, U J; Joh, T H (1990) Deduced amino acid sequence of bovine aromatic L-amino acid decarboxylase: homology to other decarboxylases. Brain Res Mol Brain Res 8:83-7