Neuroglycan C, a chondroitin sulfate proteoglycan, overcomes the abnormal behavior induced by administration of some drugs?

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Neuroglycan C(NGC), a chondroitin sulfate proteoglycan, is predominantly expressed in the brain. To clarify the roles of NGC in the brain development, we generated three strains of NGC-gene mutant mice, including NGC-knockout(NGC-KO) mice that are completely deficient in all splice variants of NGC. It has been reported that the behavioral sensitization to some psychotropic drugs is associated with up-and down-regulation of NGC gene expression. So we have investigated the relationship of several psychostimulants and the behavior of NGC-KO mice using the open field test. As expected, NGC-KO mice showed different behavior compared with wild mice. Together with that hyperactivity was observed in NGC-KO mice in the open field test, NGC-KO mice may be evaluated as an animal model of attention-deficit/hyperactivity disorder(ADHD). To make the mechanism of ADHD clear, the changes of protein patterns in the cerebral cortex of NGC-KO and wild mice were examined using two-dimensional gel electrophoresis after the administration of methamphetamine, a psychostimulant. A protein which may be related to hyperactivity induced by methamphetamine was found. As another trial for clarifying the roles of NGC, we studied the binding proteins and found that pleiotrophin was a NGC-binding protein.