Prefrontal cortex shotgun proteome analysis reveals altered calcium homeostasis and immune system imbalance in schizophrenia

Martins-de-Souza, Daniel; Gattaz, Wagner F.; Schmitt, Andrea; Rewerts, Christiane; Maccarrone, Giuseppina; Dias-Neto, Emmanuel; Turck, Christoph W.

doi:10.1007/s00406-008-0847-2

Cited by 181 publications

(133 citation statements)

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“…WDR1 is involved in actin formation and sensory perception of sound. Studies using shotgun mass spectrometry found that WDR1 was differentially expressed in the dorsolateral prefrontal cortex of schizophrenia patients (33). The linkage of bipolar disorder to chromosome 4p and haplotype analysis have implicated the WDR1 locus (34).…”

Section: Discussionmentioning

confidence: 99%

Strong synaptic transmission impact by copy number variations in schizophrenia

Glessner

Reilly

Kim

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

207

194

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Schizophrenia is a psychiatric disorder with onset in late adolescence and unclear etiology characterized by both positive and negative symptoms, as well as cognitive deficits. To identify copy number variations (CNVs) that increase the risk of schizophrenia, we performed a whole-genome CNV analysis on a cohort of 977 schizophrenia cases and 2,000 healthy adults of European ancestry who were genotyped with 1.7 million probes. Positive findings were evaluated in an independent cohort of 758 schizophrenia cases and 1,485 controls. The Gene Ontology synaptic transmission family of genes was notably enriched for CNVs in the cases (P = 1.5 × 10 −7 ). Among these, CACNA1B and DOC2A, both calcium-signaling genes responsible for neuronal excitation, were deleted in 16 cases and duplicated in 10 cases, respectively. In addition, RET and RIT2, both ras-related genes important for neural crest development, were significantly affected by CNVs. RET deletion was exclusive to seven cases, and RIT2 deletions were overrepresented common variant CNVs in the schizophrenia cases. Our results suggest that novel variations involving the processes of synaptic transmission contribute to the genetic susceptibility of schizophrenia.genetics | genomics | neurobiology

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Section: Discussionmentioning

confidence: 99%

Strong synaptic transmission impact by copy number variations in schizophrenia

Glessner

Reilly

Kim

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

207

194

View full text Add to dashboard Cite

show abstract

“…37 Usingproteomicmethods, it is possible to assess global differential protein expression between disease and control states and to obtain novel insights into disease (for reviews, see the articles by English etal, 38 Görgetal, 39 andTannuandHemby 40 ).Proteomicstudies of postmortem brain tissue from subjects with schizophrenia and from subjects with bipolar disorder have focused largely on the dorsolateral prefrontal cortex [41][42][43][44][45][46][47][48][49] and the anterior cingulate cortex. [50][51][52][53] They have demonstrated alterations in cytoskeletal, synaptic, metabolic, and mitochondrial proteins.…”

mentioning

confidence: 99%

Common Proteomic Changes in the Hippocampus in Schizophrenia and Bipolar Disorder and Particular Evidence for Involvement of Cornu Ammonis Regions 2 and 3

Föcking

Dicker²,

English³

et al. 2011

Arch Gen Psychiatry

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“…These proteins might also be potential biomarkers for schizophrenia 65 . The oligodendrocyte protein ermin was found to be upregulated in the prefrontal cortex and downregulated in the temporal cortex in two used shotgun proteomic studies 66,67 . Brockschnieder et al 68 concluded that ermin probably contributes to the maintenance and stabilization of the myelin sheath in the adult brain.…”

Section: Disturbed Macroconnectivity: Evidence From Cellular and Molementioning

confidence: 99%

Estudos transcriptômicos no contexto da conectividade perturbada em esquizofrenia

Schmitt

Reich‐Erkelenz²,

Gebicke‐Härter

et al. 2012

Arch. Clin. Psychiatry (São Paulo)

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Schizophrenia is a severe neurobiological disease with genetic and environmental factors playing a role in the pathophysiology. Several brain regions have been implicated in the disease process and are connected in complex neuronal circuits. On the cellular and molecular level, affected connectivity between these regions, involving dysfunctional myelination of neuronal axons, as well as alterations on the synaptic level and energy metabolism of neurons leading to disturbances in synaptic plasticity are major findings in post-mortem studies. Microarray studies investigating genome-wide gene expression have contributed to the findings of alterations in complex pathways in relevant brain regions in schizophrenia. Moreover, first laser-capture microdissection studies allowed the investigation of gene expression in specific groups of neurons. However, it must be kept in mind that in post-mortem studies confounding effects of medication, mRNA quality as well as the capability of the brain for neuroplastic regenerative mechanisms in individuals with a lifetime history of schizophrenia may influence the complex pattern of alterations on the molecular level. Despite these limitations, hypothesis-free transcriptome studies in brain tissue from schizophrenia patients offer a unique possibility to learn more about underlying mechanisms, leading to new insights in the pathophysiology of the disease. A, et al. / Rev Psiq Clín. 2013;40(1):10-5 Keywords: Schizophrenia, gene expression, microarray, RT-PCR, in situ hybridization, brain regions. Schmitt ResumoEsquizofrenia é uma severa doença neurobiológica com fatores genéticos e ambientais desempenhando um papel na fisiopatologia. Diversas regiões cerebrais têm sido implicadas no processo da doença e estão conectadas em complexos circuitos neuronais. Nos níveis molecular e celular, a conectividade afetada entre essas regiões, envolvendo mielinização disfuncional dos axônios neuronais, bem como as alterações no nível sináptico e metabolismo energético levando a distúrbios na plasticidade sináptica, são os maiores achados em estudos post-mortem. Estudos de microarranjos investigando a expressão gênica contribuíram para os achados de alterações em vias complexas em regiões cerebrais relevantes na esquizofrenia. Além disso, estudos utilizando microdissecção e captura a laser permitiram a investigação da expressão gênica em grupos específicos de neurônios. Entretanto, deve ser mantido em mente que em estudos post-mortem, confusos efeitos de medicação, qualidade de RNAm, bem como capacidade de mecanismos regenerativos neuroplásticos do cérebro em indivíduos com história de vida de esquizofrenia, podem influenciar o complexo padrão de alterações no nível molecular. Apesar dessas limitações, estudos transcriptômicos livres de hipóteses em tecido cerebral de pacientes esquizofrênicos oferecem uma possibilidade única para aprender mais sobre os mecanismos subjacentes, levando a novas ópticas da fisiopatologia da doença. A, et al. / Rev Psiq Clín. 2013;40(1):10-5 Palavras-cha...

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Prefrontal cortex shotgun proteome analysis reveals altered calcium homeostasis and immune system imbalance in schizophrenia

Cited by 181 publications

References 100 publications

Strong synaptic transmission impact by copy number variations in schizophrenia

Strong synaptic transmission impact by copy number variations in schizophrenia

Common Proteomic Changes in the Hippocampus in Schizophrenia and Bipolar Disorder and Particular Evidence for Involvement of Cornu Ammonis Regions 2 and 3

Estudos transcriptômicos no contexto da conectividade perturbada em esquizofrenia

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