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Analysis Of Molecular Networks In The Cerebellum In Chronic Schizophrenia: Modulation By Early Postnatal Life Stressors In Murine Models

ABSTRACT: Despite the growing importance of the cortico-cerebellar-thalamo-cortical circuit in schizophrenia, limited information is available regarding altered molecular networks in cerebellum. To identify altered protein networks, we conducted proteomic analysis of grey matter of postmortem cerebellar cortex in chronic schizophrenia subjects (n=12) and healthy individuals (n=14) followed by an extensive bioinformatic analysis. Two double-hit postnatal stress murine models for SZ were used to validate the most robust candidates.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

SUBMITTER: Ricard Rodriguez-Mias

LAB HEAD: Judit Villen

PROVIDER: PXD024937 | Pride | 2021-12-30

REPOSITORIES: Pride

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	Oxidation__M_Sites.txt	Txt
	allPeptides.txt	Txt
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	evidence.txt	Txt
	modificationSpecificPeptides.txt	Txt

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Analysis of Molecular Networks in the Cerebellum in Chronic Schizophrenia: Modulation by Early Postnatal Life Stressors in Murine Models.

Vera-Montecinos América A Rodríguez-Mias Ricard R MacDowell Karina S KS García-Bueno Borja B Bris Álvaro G ÁG Caso Javier R JR Villén Judit J Ramos Belén B

International journal of molecular sciences 20210917 18

Despite the growing importance of the cerebellum as a region highly vulnerable to accumulating molecular errors in schizophrenia, limited information is available regarding altered molecular networks with potential therapeutic targets. To identify altered networks, we conducted one-shot liquid chromatography-tandem mass spectrometry in postmortem cerebellar cortex in schizophrenia and healthy individuals followed by bioinformatic analysis (PXD024937 identifier in ProteomeXchange repository). A t ...[more]

PMID: 34576238

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ANALYSIS OF NETWORKS IN THE DORSOLATERAL PREFRONTAL CORTEX IN CHRONIC SCHIZOPHRENIA: RELEVANCE OF ALTERED IMMUNE RESPONSE

Project description:The dorsolateral prefrontal cortex (DLPFC) is the association area in the anterior part of the frontal lobe and has a crucial role in cognitive functioning and negative symptoms in SZschizophrenia. However, limited information of altered protein networks is available in this region in schizophrenia. We performed a proteomic analysis using single-shot liquid chromatography-tandem mass spectrometry of grey matter of postmortem DLPFC in chronic schizophrenia subjects (n=20) and healthy individuals (n=20) followed by bioinformatic analysis to identify altered protein networks in SZ.

2023-05-10 | PXD024939 | Pride

Human cartilage zone arrays

Project description:Objective. Identify novel genes and pathways specific to superficial (SZ), middle (MZ) and deep zones (DZ) of normal articular cartilage. Methods. Articular cartilage was obtained from knees of 4 normal human donors. The cartilage zones were dissected on a microtome. RNA was analyzed on human genome arrays. Data obtained with human tissue were compared to bovine cartilage zone specific DNA arrays. Genes differentially expressed between zones were evaluated using direct annotation for structural or functional features, and by enrichment analysis for integrated pathways or functions. Results. The greatest differences were observed between SZ and DZ in both human and bovine cartilage. The MZ was transitional between the SZ and DZ and thereby shared some of the same pathways as well as structural/functional features of the adjacent zones. Cellular functions and biological processes enriched in the SZ relative to the DZ, include most prominently ECM receptor interactions, cell adhesion molecules, regulation of actin cytoskeleton, ribosome-related functions and signaling aspects such as Interferon gamma, IL4, CDC42Rac and Jak-Stat. Two pathways were enriched in the DZ relative to the SZ, including PPARG and EGFR_SMRTE. Conclusion. These differences in cartilage zonal gene expression identify new markers and pathways that govern the unique differentiation status of chondrocyte subpopulations. 12 samples, 4 donors, 3 conditions each donor (SZ, MZ and DZ), 0 donor replicates, comparisons made between SZ, MZ and DZ to identify differentially expressed genes.

2012-07-31 | E-GEOD-39795 | biostudies-arrayexpress

Bovine cartilage zone arrays

Project description:Objective. Identify novel genes and pathways specific to superficial (SZ), middle (MZ) and deep zones (DZ) of normal articular cartilage. Methods. Articular cartilage was obtained from knees of 4 normal human donors. The cartilage zones were dissected on a microtome. RNA was analyzed on human genome arrays. Data obtained with human tissue were compared to bovine cartilage zone specific DNA arrays. Genes differentially expressed between zones were evaluated using direct annotation for structural or functional features, and by enrichment analysis for integrated pathways or functions. Results. The greatest differences were observed between SZ and DZ in both human and bovine cartilage. The MZ was transitional between the SZ and DZ and thereby shared some of the same pathways as well as structural/functional features of the adjacent zones. Cellular functions and biological processes enriched in the SZ relative to the DZ, include most prominently ECM receptor interactions, cell adhesion molecules, regulation of actin cytoskeleton, ribosome-related functions and signaling aspects such as Interferon gamma, IL4, CDC42Rac and Jak-Stat. Two pathways were enriched in the DZ relative to the SZ, including PPARG and EGFR_SMRTE. Conclusion. These differences in cartilage zonal gene expression identify new markers and pathways that govern the unique differentiation status of chondrocyte subpopulations. 6 samples, 2 bovine donors, 3 conditions each donor (SZ, MZ and DZ), 0 donor replicates, comparisons made between SZ, MZ and DZ to identify differentially expressed genes.

2012-07-31 | E-GEOD-39796 | biostudies-arrayexpress

Next-generation proteomics of brain extracellular vesicles in schizophrenia provide new clues on the altered molecular connectome

Project description:Extracellular vesicles (EVs) are tiny membranous structures capable of mediating intercellular communication. In the brain, the role(s) of EVs have been extensively studied in the context of neurological diseases, but their potential implications in the neuropathology underlying human mental disorders remain largely unexplored. Here, we investigated the potential role(s) of brain EVs in schizophrenia (SZ) by analyzing these vesicles from the three post-mortem anatomical brain regions: prefrontal cortex (PFC), hippocampus (HC) and caudate (CAU), using next-generation discovery-driven proteomics. Our results indicate that EVs from SZ-affected brains present region-specific proteins associated with abnormal GABAergic and glutamatergic transmission, as well as alterations in proteins involved in synaptic decay, abnormal brain immunity, neuronal structural imbalances and impaired cell homeostasis. Our findings also provide the first evidence that molecular exchange networks are potentially active and mediated by EVs in cognitively healthy brains. These EV-mediated networks were partially reversed and largely disrupted in brains affected by SZ.

2024-05-24 | PXD042732 | Pride

Female Drosophila melanogaster gene expression and mate choice: candidate genes underlying sexual isolation

Project description:The evolution of female choice mechanisms favouring males of their own kind is considered as crucial step during the early stages of speciation. However, although the genomics of mate choice may influence both the likelihood and speed of speciation, the identity and location of genes underlying assortative mating remain largely unknown. We used mate choice experiments and gene expression analysis of female D. melanogaster to examine three key components influencing speciation. We show that the 1,498 genes in Zimbabwean female Drosophila melanogaster whose expression levels differ when mating with more (Zimbabwean) versus less (Cosmopolitan strain) preferred males include many with high expression in the central nervous system and ovaries, are disproportionately X-linked and form a number of clusters with low recombination distance. Significant involvement of the brain and ovaries is consistent with the action of a combination of pre- and post-copulatory female choice mechanisms, while sex linkage and clustering of genes lead to high potential evolutionary rate and sheltering against the homogenizing effects of gene exchange between populations. Taken together our results imply favourable genomic conditions for the evolution of reproductive isolation through mate choice in Zimbabwean D. melanogaster and suggest that mate choice may, in general, act as an even more important engine of speciation than previously realized. We measured gene expression of adult female Drosophila melanogaster from a composite Zimbabwe (Z) strain population named SZ, produced by mixing the genomes of six Z strain isofemale lines, shortly after mating them with either SZ strain or cosmopolitan (M strain) males. Data from four replicates of each of the two treatments (SZ mated with SZ; SZ mated with M) are presented, giving a total of eight arrays.

2011-02-05 | E-GEOD-27076 | biostudies-arrayexpress

PROTEOMIC SIGNATURE OF THE CEREBELLUM IN SCHIZOPHRENIA

Project description:Malfunction of multiple regions in distributed brain circuits has been suggested to underlie the diversity of symptoms and cognitive impairments in schizophrenia. The cerebellum, as part of this circuit, may contribute to these symptoms for this reason we undertook a proteomic profile of this region. Here, we design a quantitative exploratory proteomic analysis in pooled grey matter of the cerebellum from schizophrenia and control individuals with the aim of discovering consistently altered biomarker proteins in schizophrenia.

2020-06-22 | PXD008216 | Pride

Hippocampal Subfield Transcriptome Analysis in Schizophrenia Psychosis

Project description:We have previously demonstrated functional and molecular changes in hippocampal subfields in individuals with schizophrenia (SZ) psychosis associated with hippocampal excitability. In this study, we use RNA-seq and assess global transcriptome changes in the hippocampal subfields, DG, CA3, and CA1 from individuals with SZ psychosis and controls to elucidate subfield-relevant molecular changes. We also examine changes in gene expression due to antipsychotic medication in the hippocampal subfields from our SZ ON- and OFF-antipsychotic medication cohort. We identify unique subfield-specific molecular profiles in schizophrenia postmortem samples compared to controls, implicating astrocytes in DG, immune mechanisms in CA3, and synaptic scaling in CA1. We show a unique pattern of subfield-specific effects by antipsychotic medication on gene expression levels with scant overlap of genes differentially expressed by SZ disease effect versus medication effect. These hippocampal subfield changes could provide the basis for previously observed hippocampal SZ pathology and explain the lack of full efficacy of conventional antipsychotic medication on SZ symptomatology. With further characterization, the identified distinct molecular profiles of the DG, CA3, and CA1 in SZ psychosis may serve to identify potential hippocampal-based therapeutic targets.

2020-05-11 | GSE138082 | GEO

Circadian analysis of the mouse cerebellum

Project description:The cerebellum contains a circadian clock, generating internal temporal signals. The daily oscillations of cerebellar proteins were investigated here in mice using large-scale two-dimensional differences in gel electrophoresis (2D-DIGE). Analysis of 2D-DIGE gels highlighted the rhythmic variation in the intensity of 27/588 protein spots (5%) over 24-h based on cosinor regression. Notably, rhythmic expression of most abundant cerebellar proteins was clustered in two main phases (i.e., midday and midnight), leading to bimodal distribution. Only 6 proteins identified here to be rhythmic in the cerebellum are also known to oscillate in the suprachiasmatic nuclei, including 2 proteins involved in synapse activity (Synapsin 2 (Syn2) and vesicle-fusing ATPase (Nsf)), 2 others participating in carbohydrate metabolism (triosephosphate isomerase (Tpi1) and alpha-enolase (Eno1)), and Glutamine synthetase (Glul), as well as Tubulin alpha (Tuba4a). Most oscillating cerebellar proteins were not previously identified in circadian proteomic analyses of any tissue. Strikingly, daily accumulation of mitochondrial proteins was clustered to the mid-resting phase, as previously observed for distinct mitochondrial proteins in the liver. This study highlights extensive rhythmic aspects of the cerebellar proteome.

2019-04-23 | PXD013039 | Pride

Gene expression profiles of patients with schizophrenia, bipolar disorder and healthy controls

Project description:Schizophrenia (SZ) and bipolar disorder (BD) are severe psychiatric conditions, with a lifetime prevalence of about 1%. Both disorders have a neurodevelopment component, with onset of symptoms occurring most frequently during late adolescence or early adulthood. Genetic findings indicate the existence of an overlap in genetic susceptibility across the disorders. These gene expression profiles were used to identify the molecular mechanisms that differentiate SZ and BP from healthy controls but also that distinguish both from healthy individuals. They were also used to expand an analysis from an experiment that searched molecular alterations in human induced pluripotent stem cells derived from fibroblasts from control subject and individual with schizophrenia and further differentiated to neuron to identify genes relevant for the development of schizophrenia (GSE62105). Brain tissue (frontal cortex) from 30 healthy controls, 29 bipolar disorder patients and 29 schizophrenia patients were analyzed. The reference is an in-house pool of RNA extracted from 15 human cell lines.

2014-10-11 | E-GEOD-62191 | biostudies-arrayexpress

mRNA Sequencing Reveals Altered Synaptic Vesicular Transport in Post-Mortem Cerebellum

Project description:Schizophrenia (SCZ) is a common, disabling mental illness with high heritability but complex, poorly understood genetic etiology. As the first phase of a genomic convergence analysis of SCZ, we generated 16.7 billion nucleotides of short read, shotgun sequences of cDNA from post-mortem cerebellar cortices of 14 patients and six matched controls. A rigorous analysis pipeline was developed for analysis of digital gene expression studies. Sequences aligned to approximately 33,200 transcripts in each sample, with average coverage of 450 reads per gene. Following adjustments for confounding clinical, sample and experimental sources of variation, 215 genes differed significantly in expression between cases and controls. Golgi apparatus, vesicular transport, membrane association, Zinc binding and regulation of transcription were over-represented among differentially expressed genes. Twenty three genes with altered expression and involvement in presynaptic vesicular transport, Golgi function and GABAergic neurotransmission define a unifying molecular hypothesis for dysfunction in cerebellar cortex in SCZ.

2008-11-12 | GSE12297 | GEO

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