Dopaminergic hypofunctions and prepulse inhibition deficits in mice lacking midkine

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• 作者：Shintaro Ohgake ; Eiji Shimizu ; Kenji Hashimoto ; Naoe Okamura ; Kaori Koike ; Hiroyuki Koizumi ; Mihisa Fujisaki ; Nobuhisa Kanahara ; Shingo Matsuda ; Chihiro Sutoh ; Daisuke Matsuzawa ; Hisako Muramatsu ; Tak
• 关键词：Dopaminergic system ; Neurotrophic factor ; NMDA ; Schizophrenia ; Sensorimotor gating
• 刊名：Progress in Neuro-Psychopharmacology and Biological Psychiatry
• 出版年：2009
• 出版时间：30 April 2009
• 年：2009
• 卷：33
• 期：3
• 页码：541-546
• 全文大小：592 K

文摘

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.