Depressive disorders are debilitating conditions that affect millions of individuals and create an enormous burden on society. Close to 100 billion dollars per year are spent treating patients with severe and mild forms of depression in the United States alone. However, the underlying molecular mechanisms that trigger depression remain to be elucidated so that treatment alternatives for patients that are unresponsive to the current forms of therapy can be created. A potential target for the design of novel treatment strategies is brain derived neurotrophic factor (BDNF). Compelling evidence shows that BDNF modulates affective behavior but the specific role and the mechanism of action of this neurotrophin remain elusive. We recently generated conditional mutations of BDNF using the cre recombinase/IoxP system. These mice have a pre or postnatal depletion of BDNF in the central nervous system that does not compromise their viability as the global depletion of BDNF does. These mutants display dramatic changes in behavior including hyperaggression and hypersensitivity to stress, both of which are often symptoms of depression. We propose using these mutants, and others that we are currently generating, as genetic models of depressive disorders to dissect the role of BDNF in the regulation of behavior. Different lines of mutants that through genetic manipulation have depletion or over expression of BDNF in different regions of the brain associated with mood disorders will be tested using standard behavioral models for depression and aggression. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH067817-01
Application #
6600981
Study Section
Special Emphasis Panel (ZRG1-BDCN-6 (01))
Program Officer
Winsky, Lois M
Project Start
2003-04-01
Project End
2008-03-31
Budget Start
2003-04-01
Budget End
2004-03-31
Support Year
1
Fiscal Year
2003
Total Cost
$396,250
Indirect Cost
Name
Tufts University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
039318308
City
Boston
State
MA
Country
United States
Zip Code
02111
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