Abstract

The presence of the genes for choline acetyltransferase (ChAT) and the vesicular acetylcholine transporter (VAChT) at a common genetic locus suggests that these cholinergic markers may be coordinately regulated in the healthy brain. However, evidence from Alzheimer's patients suggest that ChAT and VAChT may also be independently regulated in response to neuronal injury. We propose to develop site-directed polyclonal antifusion protein antibodies to several regions Of the rat VAChT to test the hypothesis that VAChT is a specific marker of cholinergic neurons and terminals. Antibodies will be rigorously characterized by immunoblotting and immunocytochemistry. Subsequently, these antibodies and specific antibodies to ChAT will be used to test the hypotheses that: 1) ChAT and VAChT protein are independently regulated in fimbria-fornix transection but coordinately regulated in 192IgG-saporin immunolesions, and 2) NGF will maintain the levels of VAChT protein, as established for ChAT, in axotomized medial septal neurons. Quantitative immunoblotting and cell counts of immunopositive neurons will be compared along with ChAT enzyme assays and 3H-vesamicol saturation binding to determine how ChAT and VAChT are regulated in these paradigms. The use of degeneration models and therapeutic strategies will provide a foundation for interpretation of results in pathologies such as AD.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31MH011474-02
Application #
2546314
Study Section
Neuropharmacology and Neurochemistry Review Committee (NPNC)
Project Start
1997-10-01
Project End
Budget Start
1997-10-01
Budget End
1998-05-11
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
Emory University
Department
Neurology
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322