Selective behaviors altered in plasminogen-deficient mice are reconstituted with intracerebroventricular injection of plasminogen

In vitro studies demonstrate a role for the plasminogen (Plg) system in neu rological function and recently in vivo studies show a role of the Plg syst em in neurodegeneration after the injection of an excitotoxic agent. Differ ences in the in development of neurological function, however, have not bee n demonstrated in the Plg-deficient (Plg-/-) mice compared to wild-type (WT ) mice. The role of Plg system in neurological function may relate to remod eling which occurs in response to various environmental challenges. In this study, behaviors (open field, grooming, hind-leg gait, water maze, and aco ustic startle reflex) were tested in the Plg-deficient and WT mice at 6-8 w eeks of age. Grooming, a response to the stress of an open field or for moi stening, was increased in the Plg-/--deficient mice compared to WT mice, an d the acoustic startle reflex (ASR) was markedly decreased in the Plg-/- mi ce. The reduced ASR in Plg-/- mice occurred in mice with a mixed C57BL:129 background or in mice with a C57BL background. Pig was required for the ASR , since a deficiency of the Pig activators, urokinase (uPA) or tissue Plg a ctivator (tPA), did not cause a reduction in the ASR compared to their WT c ontrol. Infusion of Plg directly into the brain was effective in restoring the ASR in the Plg-/- mice, but had no effect on the ASR of WT mice. Periph eral bolus injections of Plg or infusion into the jugular vein were ineffec tive in restoring the ASR in the Plg-/- mice. These results indicate that P ig is required for the appropriate response to the environmental challenge of a sudden loud sound. and that the response can be restored in Plg-/- mic e by directly infusing Plg into the brain. (C) 2001 Published by Elsevier S cience B.V.