Schizophrenia hippocampus has elevated expression of chondrex glycoprotein gene

Chung, Carmen; Tallerico, Teresa; Seeman, Philip

doi:10.1002/syn.10228

Cited by 60 publications

(36 citation statements)

References 23 publications

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“…The only practical approaches are to obtain brain tissue at necropsy as has been done in a few brain collections worldwide or, perhaps, to sample olfactory epithelium [Rioux et al, 2005]. Although there is some controversy [Miklos and Maleszka, 2004] and not all studies have delimited gene expression agonal signatures [Tomita et al, 2004], microarray approaches have been applied to post-mortem brain samples for schizophrenia [Mirnics et al, 2000[Mirnics et al, , 2001Hakak et al, 2001;Vawter et al, 2001Vawter et al, , 2002Hemby et al, 2002;Middleton et al, 2002;Mimmack et al, 2002;Chung et al, 2003;Tkachev et al, 2003;Aston et al, 2004;Iwamoto et al, 2004Iwamoto et al, , 2005Sugai et al, 2004]. Based in part on gene expression data, RGS4 [Chowdari et al, 2002] and SELENBP1 have been forwarded as candidate genes for the etiology of schizophrenia.…”

Section: Introductionmentioning

confidence: 98%

Evaluating the comparability of gene expression in blood and brain

Sullivan

Fan

Perou

2006

American J of Med Genetics Pt B

510

367

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The availability of an accessible tissue whose gene expression profile is similar to more inaccessible CNS tissues has the potential to advance research in neuropsychiatric disorders. We conducted secondary data analysis of transcriptional profiling of 79 human tissues for 33,698 genes using the Affymetrix U133A microarray augmented with a custom microarray (Affymetrix GNF1H), which were produced by the Genomics Institute of the Novartis Research Foundation (http://symatlas.gnf.org). Our analyses suggested that: (a) on a transcriptome level, whole blood shares significant gene expression similarities with multiple CNS tissues; (b) the median non-parametric correlation between transcripts present in both whole blood and CNS was around 0.5; (c) this correlation of 0.5 was intermediate relative to all tissues in the Novartis data set--less than for the maximum achievable value of 0.85, less than a set of immune tissues (0.64), comparable to a heterogeneous set of somatic tissues (0.57) but greater than muscle (0.48) and peripheral nervous system tissues (0.36); (d) about half of a set of candidate genes relevant to schizophrenia were expressed in both whole blood and prefrontal cortex; and (e) the expression levels of many classes of biologically relevant processes were not significantly different between whole blood and prefrontal cortex. These analyses suggest that gene expression in whole blood is neither perfectly correlated and useful nor perfectly uncorrelated and useless with gene expression in multiple brain tissues. This suggests that the cautious and thoughtful use of peripheral gene expression may be a useful surrogate for gene expression in the CNS when it has been determined that the relevant gene is expressed in both.

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Section: Introductionmentioning

confidence: 98%

Evaluating the comparability of gene expression in blood and brain

Sullivan

Fan

Perou

2006

American J of Med Genetics Pt B

510

367

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“…Many gene expression studies have been conducted using postmortem brain tissues. These studies have demonstrated increased expression of genes involved in presynaptic function 17,18 and the downregulation of myelination-related genes. 19,20 Although there is some agreement across these studies, there has been a lack of consistency because of the varying characteristics of postmortem brain tissues.…”

Section: Introductionmentioning

confidence: 99%

Dysbindin-1 and NRG-1 gene expression in immortalized lymphocytes from patients with schizophrenia

et al. 2011

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The dysbindin-1 and neuregulin-1 (NRG-1) genes are related to schizophrenia. Expression studies in postmortem brains have revealed lower expression of dysbindin-1 and higher expression of NRG-1 in brain tissue from subjects with schizophrenia. In addition to the difficulty of sampling, the use of postmortem brain tissues is not ideal because these tissues are heterogeneous with respect to biochemical parameters, lifetime history of medications and physiological status at the time of death. In contrast, medication and environmental influences that could mask the genetic basis of differences in RNA expression are removed in immortalized lymphocytes by culturing. Only a few microarray analysis studies using immortalized lymphocytes in schizophrenia have been reported, and whether immortalized lymphocytes are an appropriate alternative to neuronal tissue remains controversial. In this study, we measured the mRNA expression levels of dysbindin-1, NRG-1 and two other genes (NPY1R and GNAO1) in immortalized lymphocytes from 45 patients with schizophrenia and 45 controls using real-time quantitative reverse transcriptase-PCR. No difference was observed between patients and controls with respect to the expression of dysbindin-1, NRG-1, NPY1R or GNAO1 gene. Our findings suggest that the gene expression profile of immortalized lymphocyte from schizophrenic patients is different from that in postmortem brain tissue at least with respect to the dysbindin-1 and NRG-1 genes. Journal of Human Genetics INTRODUCTIONSchizophrenia is a complex genetic disorder that is characterized by profound disturbances of cognition, emotion and social functioning. It affects B1% of the general population world wide. The dysbindin-1 and neuregulin-1 (NRG-1) genes are related to schizophrenia, 1 and the dysbindin-1 gene is also associated with cognitive functions. [2][3][4] Furthermore, the Sandy mouse, which expresses no dysbindin-1, has been reported to have behavioral abnormalities, cognitive deficits and a synaptic dysfunction that is related to the pathophysiology of schizophrenia. [5][6][7] Identified risk variants of NRG-1 are associated with the reduced white matter volume that is observed in schizophrenic brains. 8 The NRG-1 gene spans 1.2 Mb 9 and gives rise to many structurally and functionally distinct isoforms, through alternative promoter usage. These isoforms are divided into three classic groups: 10 type I (previously known as acetylcholine receptor inducing activity, heregulin or neu differentiation factor), type II (glia growth factor) and type III (cysteine-rich domain containing), which are based on distinct amino termini. Additional NRG-1 5¢ exons have

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“…97 102 found that a number of genes related to neurotransmission (GRIN2B, GRIP2, SYT7), neurodevelopment (DAB1, SEMA5A), and intracellular signaling (PIK3R1, CACNG2) were significantly altered. 102 Chung et al 91 showed upregulation of heat shock 70 gene in schizophrenic brain. 91 A number of schizophrenia candidate genes have been found to change in PFC over the course of the life span in brain samples from control subjects via microarray: (1) RGS4 and glutamate receptor metabotropic 3 (GRM3) expression decreased across the age range, (2) PRODH and DARPP32 expression increased with age, and (3) NRG1, ERBB3, and nerve growth factor receptor showed altered expression during the years of greatest risk for the development of schizophrenia.…”

Section: Geneticsmentioning

confidence: 99%

The Neurodevelopmental Hypothesis of Schizophrenia, Revisited

Fatemi

Folsom²

2009

Schizophrenia Bulletin

707

460

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While multiple theories have been put forth regarding the origin of schizophrenia, by far the vast majority of evidence points to the neurodevelopmental model in which developmental insults as early as late first or early second trimester lead to the activation of pathologic neural circuits during adolescence or young adulthood leading to the emergence of positive or negative symptoms. In this report, we examine the evidence from brain pathology (enlargement of the cerebroventricular system, changes in gray and white matters, and abnormal laminar organization), genetics (changes in the normal expression of proteins that are involved in early migration of neurons and glia, cell proliferation, axonal outgrowth, synaptogenesis, and apoptosis), environmental factors (increased frequency of obstetric complications and increased rates of schizophrenic births due to prenatal viral or bacterial infections), and gene-environmental interactions (a disproportionate number of schizophrenia candidate genes are regulated by hypoxia, microdeletions and microduplications, the overrepresentation of pathogen-related genes among schizophrenia candidate genes) in support of the neurodevelopmental model. We relate the neurodevelopmental model to a number of findings about schizophrenia. Finally, we also examine alternate explanations of the origin of schizophrenia including the neurodegenerative model.

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Schizophrenia hippocampus has elevated expression of chondrex glycoprotein gene

Cited by 60 publications

References 23 publications

Evaluating the comparability of gene expression in blood and brain

Evaluating the comparability of gene expression in blood and brain

Dysbindin-1 and NRG-1 gene expression in immortalized lymphocytes from patients with schizophrenia

The Neurodevelopmental Hypothesis of Schizophrenia, Revisited

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