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Tissue plasminogen activator promotes the effects of corticotropin-releasing factor on the amygdala and anxiety-like behavior.

Matys T, Pawlak R, Matys E, Pavlides C, McEwen BS, Strickland S

Laboratory of Neurobiology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.

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.

Published 19 November 2004 in Proc Natl Acad Sci U S A, 101(46): 16345-50.
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