Synapses are critical sites of information transfer within the nervous system. Therefore, if synapses incur stress-induced damage, behaviors required for daily living would be severely compromised. Homeostatic mechanisms can be recruited to maintain synaptic function under adverse conditions through prior exposure to mild stress. However, the underlying mechanisms are poorly understood. We previously showed that malfunction of Drosophila glutamatergic synapses at high temperatures can be attenuated by heat pretreatment (brief exposure to sublethal temperatures). Major heat shock proteins (HSPs) upregulated by heat pretreatment are found to be partly responsible for conferring synaptic thermoprotection. In spite of this knowledge, the key synaptic mechanisms and/or proteins thermoprotected by heat shock proteins are unknown.
The specific aim of this proposal is: to elucidate which mechanisms of evoked transmitter release are thermoprotected at elevated temperatures by heat pretreatment. Future investigations stemming from these pilot experiments will allow us to identify key synaptic proteins associated with the thermoprotected mechanisms chaperoned by HSPs. This in turn will allow us to determine how HSPs interact with synaptic proteins to maintain synaptic homeostasis under stress. We seek to identify mechanisms regulating neurotransmitter release that are protected from failing at high temperatures by heat pretreatment. The general findings of our investigations will ultimately lead to the development of therapies to prevent stress-induced synaptic damage. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Small Research Grants (R03)
Project #
1R03NS060084-01
Application #
7296494
Study Section
Synapses, Cytoskeleton and Trafficking Study Section (SYN)
Program Officer
Talley, Edmund M
Project Start
2007-07-01
Project End
2008-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
1
Fiscal Year
2007
Total Cost
$75,500
Indirect Cost
Name
University of Arizona
Department
Type
Organized Research Units
DUNS #
806345617
City
Tucson
State
AZ
Country
United States
Zip Code
85721