title: Lasp1 is down-regulated in NMDA receptor antagonist-treated mice and implicated in human schizophrenia susceptibility.
abstract: Mice treated with MK-801, a non-competitive antagonist of the N-methyl-d-aspartic (NMDA) acid receptor, are important animal models for schizophrenia studies. In the present study, we compared protein expression levels in the hippocampus of mice treated with MK-801 (0.6 mg/kg) or saline once daily for 7 days. Changes in the proteome were detected by two-dimensional electrophoresis, and the six proteins exhibiting differential expression were identified by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. Down-regulation of one of these proteins, Lasp1 (LIM and SH3 protein 1), in MK-801-treated mice was confirmed by western blotting and immunohistochemical analyses. Lasp1 is a multidomain protein that may recruit signaling molecules to the actin-based cytoskeleton and is known to concentrate in synaptic sites of hippocampal neurons. We next investigated whether polymorphisms in the human LASP1 gene were associated with schizophrenia in the Korean population. A single-nucleotide polymorphism in the LASP1 gene promoter region was associated with schizophrenia susceptibility. Our results suggest that LASP1 might be associated with NMDA receptor antagonism and schizophrenia susceptibility and, thus, might be involved in the pathophysiology of schizophrenia.
authors.affiliation: Department of Microbiology, College of Medicine, Soonchunhyang University, Cheonan 330-090, Republic of Korea.
authors.forename: Jaesoon
authors.initials: J
authors.lastname: Joo
authors.forename: Soojeong
authors.initials: S
authors.lastname: Lee
authors.forename: Seong-Su
authors.initials: SS
authors.lastname: Nah
authors.forename: Young Ock
authors.initials: YO
authors.lastname: Kim
authors.forename: Duk-Soo
authors.initials: DS
authors.lastname: Kim
authors.forename: Se-Hoon
authors.initials: SH
authors.lastname: Shim
authors.forename: Young
authors.initials: Y
authors.lastname: Hwangbo
authors.forename: Hyung-Kee
authors.initials: HK
authors.lastname: Kim
authors.forename: Jun-Tack
authors.initials: JT
authors.lastname: Kwon
authors.forename: Jong Woo
authors.initials: JW
authors.lastname: Kim
authors.forename: Ho-Yeon
authors.initials: HY
authors.lastname: Song
authors.forename: Hak-Jae
authors.initials: HJ
authors.lastname: Kim
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors* / Q000235:genetics*; D000328:Adult; D000818:Animals; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics*; D006801:Humans; D060588:LIM Domain Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008875:Middle Aged; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D011897:Random Allocation; D056910:Republic of Korea / Q000453:epidemiology; D012559:Schizophrenia / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D018398:Homeodomain Proteins; C096353:LASP1 protein, human; D060588:LIM Domain Proteins; C490692:Lasp1 protein, mouse; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate