Reelin down-regulation in mice and psychosis endophenotypes

Tueting, Patricia; Doueiri, Mohemed Salim; Guidotti, Alessandro; Davis, John M.; Costa, E.

doi:10.1016/j.neubiorev.2006.04.001

Cited by 87 publications

(62 citation statements)

References 104 publications

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“…Our finding is in line with evidence on relevant RELN functions in both maturation of the brain as well as its plasticity by synapse remodelling, 70,71,[87][88][89][90][91] crucial for cognitive abilities. 92 Also a recent mouse study, 93 as well as our previous QTL genome-wide study on the same Finnish families, 19 provide further support for the role of RELN in learning and memory processes.…”

Section: Association Of Reelin With Working Memorysupporting

confidence: 91%

Replication of linkage on chromosome 7q22 and association of the regional Reelin gene with working memory in schizophrenia families

et al. 2007

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Schizophrenia is a common and complex mental disorder. Hereditary factors are important for its etiology, but despite linkage signals reported to several chromosomal regions in different populations, final identification of predisposing genes has remained a challenge. Utilizing a large family-based schizophrenia study sample from Finland, we have identified several linked loci: 1q32.2-q42, 2q, 4q31, 5q and 7q22. In this study, an independent sample of 352 nuclear schizophrenia families (n = 1626) allowed replication of linkage on 7q21-32. In a sample of 245 nuclear families (n = 1074) originating from the same geographical region as the families revealing the linkage, SNP and microsatellite association analyses of the four regional candidate genes, GRM3, RELN, SEMA3A and VGF, revealed no significant association to the clinical diagnosis of schizophrenia. Instead, quantifiable trait component analyses with neuropsychological endophenotypes available from 186 nuclear families (n = 861) of the sample showed significant association to RELN variants for traits related to verbal (P = 0.000003) and visual working memory (P = 0.002), memory (P = 0.002) and executive functioning (P = 0.002). Trait-associated allele-positive subjects scored lower in the tests measuring working memory (P = 0.0004-0.0000000004), memory (P = 0.02-0.0001) and executive functioning (P = 0.001). Our findings suggest that allelic variants of RELN contribute to the endophenotypes of schizophrenia.

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Section: Association Of Reelin With Working Memorysupporting

confidence: 91%

Replication of linkage on chromosome 7q22 and association of the regional Reelin gene with working memory in schizophrenia families

et al. 2007

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“…Although the reeler mice showed normal social interaction and working memory (84,85), mice with epigenetic hypermethylation of reelin promoter region by methionine exhibited reduced social interaction in a novel environment (86). Moreover, the reeler mice showed reduced spontaneous locomotor activity re sponding to treatment with olanzapine, deficits in working memory, and impaired PPI, but no alteration of spatial learning (85, 87).…”

Section: Reelinmentioning

confidence: 99%

Behavioral Phenotypes for Negative Symptoms in Animal Models of Schizophrenia

Miyamoto

Nitta

2014

J Pharmacol Sci

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Abstract.A devastating psychiatric disorder, schizophrenia is characterized by three major symptoms, positive and negative symptoms and cognitive deficit. Almost all current therapeutic drugs for schizophrenia have efficacy for positive symptoms, and weak efficacy for negative and cognitive deficit. In particular, social withdrawal, diminished motivation, and anhedonia as the depressive aspects of negative symptoms are resistant to the treatment of antipsychotic drugs. Therefore, there is a need for development of new therapeutic drugs for negative symptoms of schizophrenia, and it is necessary to have comprehensive animal models to understand the neuro biological foundations of their symptoms. In this review, we represent the behavioral phenotypes in available animal models of schizophrenia for drug discovery, focusing on the depressive aspects of negative symptoms. We mention here animal models based on the pathology and epidemiology of schizophrenia, e.g., the pharmacological, neurodevelopmental, genetic, and geneenvironment combination models. The animal models of schizophrenia are developed by various approaches and are assessed, but there are few models demonstrating negative symptoms with sensitivities to available therapeutic drugs. The development of comprehensive animal model reflecting negative symptoms and of novel compounds that can remedy them provide certain insight into the neuro biological process of schizophrenia and also point the way to a new therapeutic strategy.

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“…The molecular mechanisms for this have been reviewed in substantial detail before (7)(8)(9)(10). A schematic summary of the signaling pathway that is activated by Apoer2 and Vldlr is also shown in Fig.…”

Section: Apoer2 and Vldlrmentioning

confidence: 99%

Expanding functions of lipoprotein receptors

Herz

Chen

Masiulis

et al. 2009

Journal of Lipid Research

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Lipoprotein receptors are evolutionarily ancient proteins that are expressed on the surface of many cell types. Beginning with the appearance of the first primitive multicellular organisms, several structurally and functionally distinct families of lipoprotein receptors evolved. Originally, these cell surface proteins were thought to merely mediate the traffic of lipids and nutrients between cells and, in some cases, by functioning as scavenger receptors, remove other kinds of macromolecules, such as proteases and protease inhibitors from the extracellular space and the cell surface. Over the last decade, this picture has fundamentally changed. We now appreciate that many of these receptors are not mere cargo transporters; they are deeply embedded in the machinery by which cells communicate with each other. By physically interacting and coevolving with fundamental signaling pathways, lipoprotein receptors have occupied essential and surprisingly diverse functions that are indispensable for integrating the complex web of cellular signal input during development and in differentiated tissues. Lipid transport through the circulation, the extracellular space, and across the plasma membrane involves the concerted action of a wide range of cell surface receptors, lipid carrier and transfer proteins, enzymes, and cellular transporters. As an evolutionarily ancient process, it probably arose to distribute essential nutritional or endogenously synthesized lipids and hormones but also lipid modified signaling proteins and other associated macromolecules between increasingly metabolically specialized tissues. Lipoprotein receptors are among the oldest components of this complex biochemical system. These cell surface receptors fall into two major groups: endocytic receptors that bind their cargo in the form of lipid carrying lipoproteins and mediate their internalization and eventually lysosomal delivery, and a second group that promotes lipid exchange at the plasma membrane without cellular uptake of the protein component of the particle. In addition to their specialized functions as mediators of cellular lipid uptake, lipoprotein receptors have, over the last few years, also been recognized for often unrelated roles as cellular signal transducers or signal modulators. In this review, we will restrict ourselves to only one particularly versatile subgroup of these receptors, the LDL receptor gene family (Fig. 1), and its expanding functions in the nervous system. ROLES OF THE LDL RECEPTOR GENE FAMILY IN THE NERVOUS SYSTEMSeveral members of the LDL receptor gene family are involved in a wide range of signaling pathways that control fundamental developmental processes in the embryo, as well as tissue remodeling in the adult organism. Here, the expanding roles of the gene family in the nervous system deserve particular attention. First, a stream of evidence is emerging that several members of the family are directly or indirectly involved in neuronal survival and degeneration, specifically in the incompletely understo...

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Reelin down-regulation in mice and psychosis endophenotypes

Cited by 87 publications

References 104 publications

Replication of linkage on chromosome 7q22 and association of the regional Reelin gene with working memory in schizophrenia families

Replication of linkage on chromosome 7q22 and association of the regional Reelin gene with working memory in schizophrenia families

Behavioral Phenotypes for Negative Symptoms in Animal Models of Schizophrenia

Expanding functions of lipoprotein receptors

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