Meta-Analysis of Transcriptomic Data of Dorsolateral Prefrontal Cortex and of Peripheral Blood Mononuclear Cells Identifies Altered Pathways in Schizophrenia

Petralia, Maria Cristina; Saraceno, Andrea; Pennisi, Manuela; Basile, Maria Sofia; Fagone, Paolo; Bramantı, Placido; Nicoletti, Ferdinando; Cavalli, Eugenio

doi:10.3390/genes11040390

Cited by 14 publications

(10 citation statements)

References 95 publications

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“…It should be noted that none of the previously described genes were found to be modulated in our analysis. The use of whole-genome transcriptomic analyses has largely been used in the past few years to study autoimmune disorders, cancer, and neurodegenerative and neuropsychiatric diseases [ 17 , 35 , 36 , 37 , 38 ], in order to shed light on their pathogenetic mechanisms [ 39 , 40 , 41 ] and to identify potential therapeutic targets [ 42 , 43 , 44 , 45 ]. In the present study, we showed a common transcriptomic signature between SCZ and T2DM, suggesting potential overlapping pathogenetic processes.…”

Section: Discussionmentioning

confidence: 99%

“…Alterations of the transcriptome have lately been explored to characterize the molecular and cellular processes in complex diseases [ 13 , 14 ]. Significant numbers of studies have independently characterized the gene expression signatures of SCZ [ 15 , 16 , 17 ] and T2DM [ 18 , 19 ], but no attempt has been made to establish shared gene signatures, associated regulators, and biological processes between SCZ and T2DM. Therefore, the molecular signatures and pathways associated with an increased T2DM risk in SCZ remain unclear.…”

Section: Introductionmentioning

confidence: 99%

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Identification of Common Pathogenetic Processes between Schizophrenia and Diabetes Mellitus by Systems Biology Analysis

Rahman

Islam²,

Nicoletti

et al. 2021

Genes

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Schizophrenia (SCZ) is a psychiatric disorder characterized by both positive symptoms (i.e., psychosis) and negative symptoms (such as apathy, anhedonia, and poverty of speech). Epidemiological data show a high likelihood of early onset of type 2 diabetes mellitus (T2DM) in SCZ patients. However, the molecular processes that could explain the epidemiological association between SCZ and T2DM have not yet been characterized. Therefore, in the present study, we aimed to identify underlying common molecular pathogenetic processes and pathways between SCZ and T2DM. To this aim, we analyzed peripheral blood mononuclear cell (PBMC) transcriptomic data from SCZ and T2DM patients, and we detected 28 differentially expressed genes (DEGs) commonly modulated between SCZ and T2DM. Inflammatory-associated processes and membrane trafficking pathways as common biological processes were found to be in common between SCZ and T2DM. Analysis of the putative transcription factors involved in the regulation of the DEGs revealed that STAT1 (Signal Transducer and Activator of Transcription 1), RELA (v-rel reticuloendotheliosis viral oncogene homolog A (avian)), NFKB1 (Nuclear Factor Kappa B Subunit 1), and ERG (ETS-related gene) are involved in the expression of common DEGs in SCZ and T2DM. In conclusion, we provide core molecular signatures and pathways that are shared between SCZ and T2DM, which may contribute to the epidemiological association between them.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification of Common Pathogenetic Processes between Schizophrenia and Diabetes Mellitus by Systems Biology Analysis

Rahman

Islam²,

Nicoletti

et al. 2021

Genes

Self Cite

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“…Dorso-lateral PFCx weaker processing of sensory information from thalamus is in fact associated with hallucination experiences which are common in > 50% of the SCZ patients ( Daskalakis et al., 2020 ). The molecular studies point at parvalbumin positive (PV+) GABAergic interneurons and cortical pyramidal cells networks as both altered in SCZ PFCx and across species in SCZ models ( Chung et al., 2018 ; Petralia et al., 2020 ; Wang et al., 2020 ; Weidenauer et al., 2020 ). Dopaminergic ascending terminals reaching these neurons are also hypofunctional ( Rao et al., 2019 ).…”

Section: Section 2: Dr Alterations In Schizophreniamentioning

confidence: 99%

Dopamine Receptor Subtypes, Physiology and Pharmacology: New Ligands and Concepts in Schizophrenia

Martel¹,

McArthur²

2020

Front. Pharmacol.

150

125

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Dopamine receptors are widely distributed within the brain where they play critical modulator roles on motor functions, motivation and drive, as well as cognition. The identification of five genes coding for different dopamine receptor subtypes, pharmacologically grouped as D1- (D1 and D5) or D2-like (D2S, D2L, D3, and D4) has allowed the demonstration of differential receptor function in specific neurocircuits. Recent observation on dopamine receptor signaling point at dopamine—glutamate-NMDA neurobiology as the most relevant in schizophrenia and for the development of new therapies. Progress in the chemistry of D1- and D2-like receptor ligands (agonists, antagonists, and partial agonists) has provided more selective compounds possibly able to target the dopamine receptors homo and heterodimers and address different schizophrenia symptoms. Moreover, an extensive evaluation of the functional effect of these agents on dopamine receptor coupling and intracellular signaling highlights important differences that could also result in highly differentiated clinical pharmacology. The review summarizes the recent advances in the field, addressing the relevance of emerging new targets in schizophrenia in particular in relation to the dopamine – glutamate NMDA systems interactions.

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“…Several other human-specific regDMRs overlapped genes involved in neurodevelopment (FAM198B, PHACTR1, and DIP2C in the cerebellum) and neurodevelopmental disorders, including autism spectrum disorder (ANKS1B, DIP2C, and DLGAP1 in the cerebellum) and schizophrenia (FAM193A in the DLPFC and ANKS1B, DLGAP1, and DLEU7 in the cerebellum; Figs 2B and 3B and 3C) [36][37][38][39][40][41][42][43]. These results are consistent with previous studies [15,16] and may reflect species differences in development, as well as potentially greater human vulnerability to neuropsychiatric disorders [44][45][46].…”

Section: Plos Geneticsmentioning

confidence: 98%

Comparative analysis reveals distinctive epigenetic features of the human cerebellum

et al. 2021

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Identifying the molecular underpinnings of the neural specializations that underlie human cognitive and behavioral traits has long been of considerable interest. Much research on human-specific changes in gene expression and epigenetic marks has focused on the prefrontal cortex, a brain structure distinguished by its role in executive functions. The cerebellum shows expansion in great apes and is gaining increasing attention for its role in motor skills and cognitive processing, including language. However, relatively few molecular studies of the cerebellum in a comparative evolutionary context have been conducted. Here, we identify human-specific methylation in the lateral cerebellum relative to the dorsolateral prefrontal cortex, in a comparative study with chimpanzees (Pan troglodytes) and rhesus macaques (Macaca mulatta). Specifically, we profiled genome-wide methylation levels in the three species for each of the two brain structures and identified human-specific differentially methylated genomic regions unique to each structure. We further identified which differentially methylated regions (DMRs) overlap likely regulatory elements and determined whether associated genes show corresponding species differences in gene expression. We found greater human-specific methylation in the cerebellum than the dorsolateral prefrontal cortex, with differentially methylated regions overlapping genes involved in several conditions or processes relevant to human neurobiology, including synaptic plasticity, lipid metabolism, neuroinflammation and neurodegeneration, and neurodevelopment, including developmental disorders. Moreover, our results show some overlap with those of previous studies focused on the neocortex, indicating that such results may be common to multiple brain structures. These findings further our understanding of the cerebellum in human brain evolution.

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Meta-Analysis of Transcriptomic Data of Dorsolateral Prefrontal Cortex and of Peripheral Blood Mononuclear Cells Identifies Altered Pathways in Schizophrenia

Cited by 14 publications

References 95 publications

Identification of Common Pathogenetic Processes between Schizophrenia and Diabetes Mellitus by Systems Biology Analysis

Identification of Common Pathogenetic Processes between Schizophrenia and Diabetes Mellitus by Systems Biology Analysis

Dopamine Receptor Subtypes, Physiology and Pharmacology: New Ligands and Concepts in Schizophrenia

Comparative analysis reveals distinctive epigenetic features of the human cerebellum

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