Tissue plasminogen activator in the amygdala is critical for stress-induced anxiety-like behavior.
Although neuronal stress circuits have been identified, little is known about the mechanisms that underlie the stress-induced neuronal plasticity leading to fear and anxiety. Here we found that the serine protease tissue-plasminogen activator (tPA) was upregulated in the central and medial amygdala by acute restraint stress, where it promoted stress-related neuronal remodeling and was subsequently inhibited by plasminogen activator inhibitor-1 (PAI-1). These events preceded stress-induced increases in anxiety-like behavior of mice. Mice in which the tPA gene has been disrupted did not show anxiety after up to three weeks of daily restraint and showed attenuated neuronal remodeling as well as a maladaptive hormonal response. These studies support the idea that tPA is critical for the development of anxiety-like behavior after stress.
Pawlak
Robert
R
Laboratory of Neurobiology and Genetics, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA.
Magarinos
Ana Maria
AM
Melchor
Jerry
J
McEwen
Bruce
B
Strickland
Sidney
S
D000679:Amygdala / Q000166:cytology / Q000201:enzymology*; D000818:Animals; D001008:Anxiety Disorders / Q000201:enzymology* / Q000503:physiopathology; D001522:Behavior, Animal / Q000502:physiology; D002908:Chronic Disease; D003345:Corticosterone / Q000097:blood; D005260:Female; D019922:GAP-43 Protein / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009434:Neural Pathways / Q000166:cytology / Q000201:enzymology*; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000201:enzymology*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000201:enzymology* / Q000503:physiopathology; D010959:Tissue Plasminogen Activator / Q000172:deficiency* / Q000235:genetics
D019922:GAP-43 Protein; D017395:Plasminogen Activator Inhibitor 1; D020928:Mitogen-Activated Protein Kinases; D010959:Tissue Plasminogen Activator; D003345:Corticosterone