Tissue plasminogen activator promotes the effects of corticotropin-releasing factor on the amygdala and anxiety-like behavior.
Stress-induced plasticity in the brain requires a precisely orchestrated sequence of cellular events involving novel as well as well known mediators. We have previously demonstrated that tissue plasminogen activator (tPA) in the amygdala promotes stress-induced synaptic plasticity and anxiety-like behavior. Here, we show that tPA activity in the amygdala is up-regulated by a major stress neuromodulator, corticotropin-releasing factor (CRF), acting on CRF type-1 receptors. Compared with WT, tPA-deficient mice responded to CRF treatment with attenuated expression of c-fos (an indicator of neuronal activation) in the central and medial amygdala but had normal c-fos responses in paraventricular nuclei. They exhibited reduced anxiety-like behavior to CRF but had a sustained corticosterone response after CRF administration. This effect of tPA deficiency was not mediated by plasminogen, because plasminogen-deficient mice demonstrated normal behavioral and hormonal changes to CRF. These studies establish tPA as an important mediator of cellular, behavioral, and hormonal responses to CRF.
Matys
Tomasz
T
Laboratory of Neurobiology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Pawlak
Robert
R
Matys
Elzbieta
E
Pavlides
Constantine
C
McEwen
Bruce S
BS
Strickland
Sidney
S
D000679:Amygdala / Q000187:drug effects* / Q000502:physiology*; D000818:Animals; D001007:Anxiety / Q000209:etiology* / Q000503:physiopathology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010958:Plasminogen / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000187:drug effects / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000099052:CRF Receptor, Type 1
D016760:Proto-Oncogene Proteins c-fos; D018019:Receptors, Corticotropin-Releasing Hormone; D011994:Recombinant Proteins; D000099052:CRF Receptor, Type 1; D010958:Plasminogen; D003346:Corticotropin-Releasing Hormone; D010959:Tissue Plasminogen Activator