title: Dopaminergic hypofunctions and prepulse inhibition deficits in mice lacking midkine.
abstract: 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.
authors.affiliation: Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Ohgake
authors.forename: Eiji
authors.initials: E
authors.lastname: Shimizu
authors.forename: Kenji
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Naoe
authors.initials: N
authors.lastname: Okamura
authors.forename: Kaori
authors.initials: K
authors.lastname: Koike
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Koizumi
authors.forename: Mihisa
authors.initials: M
authors.lastname: Fujisaki
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Kanahara
authors.forename: Shingo
authors.initials: S
authors.lastname: Matsuda
authors.forename: Chihiro
authors.initials: C
authors.lastname: Sutoh
authors.forename: Daisuke
authors.initials: D
authors.lastname: Matsuzawa
authors.forename: Hisako
authors.initials: H
authors.lastname: Muramatsu
authors.forename: Takashi
authors.initials: T
authors.lastname: Muramatsu
authors.forename: Masaomi
authors.initials: M
authors.lastname: Iyo
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D016207:Cytokines / Q000172:deficiency*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000378:metabolism / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000502:physiology; D007398:Interpersonal Relations; D051379:Mice; D008810:Mice, Inbred C57BL / Q000378:metabolism; D008811:Mice, Inbred DBA / Q000378:metabolism; D018345:Mice, Knockout; D000078792:Midkine; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D009433:Neural Inhibition / Q000187:drug effects / Q000235:genetics*; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D011869:Radioligand Assay / Q000379:methods; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D013216:Reflex, Startle / Q000187:drug effects / Q000235:genetics*; D014316:Tritium / Q000378:metabolism
chemical_list: D016207:Cytokines; D018492:Dopamine Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D014316:Tritium; D000078792:Midkine; D004298:Dopamine