期刊
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
卷 33, 期 3, 页码 541-546出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pnpbp.2009.02.005
关键词
Dopaminergic system; Neurotrophic factor; NMDA; Schizophrenia; Sensorimotor gating
资金
- Ministry of Education, Culture, Sports, Science and Technology, Japan
- Mitsubishi Pharma Research Foundation
- Uehara Memorial Foundation.
Midkine is a 13-kDa retinoic acid-induced heparin-binding growth factor involved in various biological phenomena such as cell migration, neurogenesis, and tissue repair. We previously demonstrated that midkine-deficient (Mdk(-/-)) mice exhibited a delayed hippocampal development with impaired working memory and increased anxiety only at the age of 4 weeks. To assess whether midkine gene could play important roles in development and maintenance of central nervous system, we investigated biochemical and behavioral parameters in dopamine and glutamate neurotransmission of Mdk(-/-) mice. The Mdk(-/-) mice exhibited a hypodopaminergic state (i.e., decreased levels of dopamine and its receptors in the striatum) with no alterations of glutamatergic system (i.e., normal level of glutamate, glutamine, glycine, D-serine, L-serine, and NMDA receptors in the frontal cortex and hippocampus). We also found prepulse inhibition deficits reversed by clozapine and haloperidol in the Mdk(-/-) mice. Our results suggested that midkine deficiency may be related to neurochemical and behavioral dysfunctions in dopaminergic system. (C) 2009 Elsevier Inc. All rights reserved.
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