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RATIONALE Schizophrenia is characterized by disturbances in sensorimotor gating and attentional processes, which can be measured by prepulse inhibition (PPI) and latent inhibition (LI), respectively. Research has implicated dysfunction of neurotransmission at the NMDA-type glutamate receptor in this disorder. OBJECTIVES This study was conducted to examine(More)
To support the role of DISC1 in human psychiatric disorders, we identified and analyzed two independently derived ENU-induced mutations in Exon 2 of mouse Disc1. Mice with mutation Q31L showed depressive-like behavior with deficits in the forced swim test and other measures that were reversed by the antidepressant bupropion, but not by rolipram, a(More)
The GTF2IRD1 general transcription factor is a candidate for involvement in the varied cognitive and neurobehavioral symptoms of the microdeletion disorder, Williams-Beuren syndrome (WBS). We show that mice with heterozygous or homozygous disruption of Gtf2ird1 exhibit decreased fear and aggression and increased social behaviors. These findings are(More)
The N-methyl-D-aspartate receptor (NMDAR), a major excitatory ligand-gated ion channel in the central nervous system (CNS), is a principal mediator of synaptic plasticity. Here we report that neuropilin tolloid-like 1 (Neto1), a complement C1r/C1s, Uegf, Bmp1 (CUB) domain-containing transmembrane protein, is a novel component of the NMDAR complex critical(More)
Significant advances have been made in understanding the role of disrupted-in-schizophrenia-1 (DISC1) in the brain and accumulating findings suggest the possible implication of DISC1 in the regulation of dopamine (DA) function. A mutation in the second exon of DISC1 at L100P leads to the development of schizophrenia-related behavior in mutant mice(More)
RATIONALE Schizophrenic patients demonstrate prominent negative and cognitive symptoms that are poorly responsive to antipsychotic treatment. Abnormal glutamatergic neurotransmission may contribute to these pathophysiological dimensions of schizophrenia. OBJECTIVE We examined the involvement of the glycine coagonist site on the N-methyl-D: -aspartate(More)
BACKGROUND Glycogen synthase kinase-3 (GSK-3) is a widely expressed and highly conserved serine/threonine protein kinase encoded by two genes that generate two related proteins: GSK-3alpha and GSK-3beta. Mice lacking a functional GSK-3alpha gene were engineered in our laboratory; they are viable and display insulin sensitivity. In this study, we have(More)
Disrupted-In-Schizophrenia-1 (DISC1) is a strong genetic risk factor associated with psychiatric disorders. Two distinct mutations in the second exon of the DISC1 gene (Q31L and L100P) lead to either depression- or schizophrenia-like behavior in mice. Both phosphodiesterase-4B (PDE4B) and glycogen synthase kinase-3 (GSK-3) have common binding sites on(More)
DISC1 (Disrupted-in-schizophrenia 1) is a strong candidate susceptibility gene for psychiatric disease that was originally discovered in a family with a chromosomal translocation severing this gene. Although the family members with the translocation had an identical genetic mutation, their clinical diagnosis and presentation varied significantly.(More)
Chronic psychoemotional stress of social defeats produces development of experimental anxious depression in male mice similar to this disorder in humans. 5-HT and 5-HIAA levels, TPH and MAO A activities, 5-HT1A-receptors in different brain areas were investigated at different stages of development of experimental disorder. It has been shown that initial(More)