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Publication : Impaired explorative behavior and neophobia in genetically modified mice lacking or overexpressing the extracellular serine protease inhibitor neuroserpin.

First Author  Madani R Year  2003
Journal  Mol Cell Neurosci Volume  23
Issue  3 Pages  473-94
PubMed ID  12837630 Mgi Jnum  J:84427
Mgi Id  MGI:2667578 Doi  10.1016/s1044-7431(03)00077-0
Citation  Madani R, et al. (2003) Impaired explorative behavior and neophobia in genetically modified mice lacking or overexpressing the extracellular serine protease inhibitor neuroserpin. Mol Cell Neurosci 23(3):473-94
abstractText  Neuroserpin is a neural serpin that inhibits the extracellular protease tissue-type plasminogen activator (tPA). We have generated neuroserpin-deficient mice which are viable and healthy. Zymographic analysis of neuroserpin-deficient brain showed unaltered tPA activity, suggesting that other inhibitors contribute to the regulation of tPA and may compensate for the defect. Analysis of explorative behavior revealed selective reduction of locomotor activity in novel environments, an anxiety-like response on the O-maze, and a neophobic response to novel objects. Mice overexpressing neuroserpin under the control of the Thy1.2 promoter are known to have a reduced brain tPA activity. They showed reduced center exploration in the open-field test and, like neuroserpin-deficient mice, a neophobic phenotype in the novel object test. Our results implicate neuroserpin in the regulation of emotional behavior through a mechanism that is at least in part independent of tPA activity. They are the first evidence for a role of protease inhibitors in mood regulation.
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