Dopaminergic hypofunctions and prepulse inhibition deficits in mice lacking midkine.
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.
Ohgake
Shintaro
S
Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670, Japan.
Shimizu
Eiji
E
Hashimoto
Kenji
K
Okamura
Naoe
N
Koike
Kaori
K
Koizumi
Hiroyuki
H
Fujisaki
Mihisa
M
Kanahara
Nobuhisa
N
Matsuda
Shingo
S
Sutoh
Chihiro
C
Matsuzawa
Daisuke
D
Muramatsu
Hisako
H
Muramatsu
Takashi
T
Iyo
Masaomi
M
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
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