Mitogen-activated protein kinase (MAPK) signalling corresponds with distinct behavioural profiles in a rat model of maternal immune activation

Deane, Ashley R.; Potemkin, Nikita; Ward, Ryan D.

doi:10.1016/j.bbr.2020.112876

Cited by 9 publications

(7 citation statements)

References 40 publications

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“…Previously, a meta-analysis demonstrated that people with SCZ are more likely to have infectious hepatitis, which could be attributed to behavioral, immunological parameters, or both 72 . It is also shown that expression levels of mitogen-activated protein kinase (MAPK) 73 and forkhead box O (FOXO) pathway-related genes 74 are altered in SCZ. Association between relaxin polymorphisms and SCZ also suggests that the relaxin pathway plays a role in the development of SCZ 75 .…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis of long non-coding RNA-associated competing endogenous RNA network in schizophrenia

Sabaie

Moghaddam

et al. 2021

Sci Rep

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Schizophrenia (SCZ) is a serious psychiatric condition with a 1% lifetime risk. SCZ is one of the top ten global causes of disabilities. Despite numerous attempts to understand the function of genetic factors in SCZ development, genetic components in SCZ pathophysiology remain unknown. The competing endogenous RNA (ceRNA) network has been demonstrated to be involved in the development of many kinds of diseases. The ceRNA hypothesis states that cross-talks between coding and non-coding RNAs, including long non-coding RNAs (lncRNAs), via miRNA complementary sequences known as miRNA response elements, creates a large regulatory network across the transcriptome. In the present study, we developed a lncRNA-related ceRNA network to elucidate molecular regulatory mechanisms involved in SCZ. Microarray datasets associated with brain regions (GSE53987) and lymphoblasts (LBs) derived from peripheral blood (sample set B from GSE73129) of SCZ patients and control subjects containing information about both mRNAs and lncRNAs were downloaded from the Gene Expression Omnibus database. The GSE53987 comprised 48 brain samples taken from SCZ patients (15 HPC: hippocampus, 15 BA46: Brodmann area 46, 18 STR: striatum) and 55 brain samples taken from control subjects (18 HPC, 19 BA46, 18 STR). The sample set B of GSE73129 comprised 30 LB samples (15 patients with SCZ and 15 controls). Differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) were identified using the limma package of the R software. Using DIANA-LncBase, Human MicroRNA Disease Database (HMDD), and miRTarBase, the lncRNA- associated ceRNA network was generated. Pathway enrichment of DEmRNAs was performed using the Enrichr tool. We developed a protein–protein interaction network of DEmRNAs and identified the top five hub genes by the use of STRING and Cytoscape, respectively. Eventually, the hub genes, DElncRNAs, and predictive miRNAs were chosen to reconstruct the subceRNA networks. Our bioinformatics analysis showed that twelve key DEmRNAs, including BDNF, VEGFA, FGF2, FOS, CD44, SOX2, NRAS, SPARC, ZFP36, FGG, ELAVL1, and STARD13, participate in the ceRNA network in SCZ. We also identified DLX6-AS1, NEAT1, MINCR, LINC01094, DLGAP1-AS1, BABAM2-AS1, PAX8-AS1, ZFHX4-AS1, XIST, and MALAT1 as key DElncRNAs regulating the genes mentioned above. Furthermore, expression of 15 DEmRNAs (e.g., ADM and HLA-DRB1) and one DElncRNA (XIST) were changed in both the brain and LB, suggesting that they could be regarded as candidates for future biomarker studies. The study indicated that ceRNAs could be research candidates for investigating SCZ molecular pathways.

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Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis of long non-coding RNA-associated competing endogenous RNA network in schizophrenia

Sabaie

Moghaddam

et al. 2021

Sci Rep

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“…The PI3K/AKT and MAPK signaling pathways are important in cellular activities, including cell growth and proliferation [ 20 , 21 ]. It has been reported that the phosphorylation of AKT and ERK is essential for the regulation of prostate diseases [ 28 , 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…The mitogen-activated protein kinase (MAPK) pathway is a signaling network that plays important roles in cell proliferation, division, and apoptosis [ 20 ]. The three major MAPKs pathways in mammalian cells are the extracellular signal-regulated protein kinase (ERK), p38 kinase, and Jun N-terminal-kinase (JNK) pathways.…”

Section: Introductionmentioning

confidence: 99%

Resveratrol Attenuates the Proliferation of Prostatic Stromal Cells in Benign Prostatic Hyperplasia by Regulating Cell Cycle Progression, Apoptosis, Signaling Pathways, BPH Markers, and NF-κB Activity

Jang

Song

Lee

et al. 2021

IJMS

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Resveratrol can inhibit cell proliferation and metastasis and induce apoptosis. However, the mechanisms of action through which resveratrol inhibits the abnormal proliferation of prostate stromal cells, causing prostatic hyperplasia, have not been fully elucidated. Here, we evaluated the inhibitory effects of resveratrol on cell° proliferation associated with prostatic hyperplasia using WPMY-1 cells. Our results showed that resveratrol inhibited the proliferation of WPMY-1 cells via the induction of G0/G1-phase cell cycle arrest, which was caused by downregulated expression of cyclins and cyclin-dependent kinases regulated by increased p21WAF1 and p27KIP1 expression level. In addition, resveratrol treatment suppressed the phosphorylation of phosphatidylinositol 3-kinase/AKT and extracellular signal-regulated kinase 1/2. The expression levels of molecular markers affecting prostate development were also reduced by treatment with resveratrol. Finally, resveratrol attenuated the binding activity of the transcription factor nuclear factor-κB in WPMY-1 cells, and accelerated apoptotic cell death via intrinsic cascade pathway. These results indicate that resveratrol may be useful for the prevention or treatment of prostatic hyperplasia.

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“…With MAPK as a gross marker of signal transduction, these findings suggest that alterations in cellular communication within PFC are detrimental to sensory processing and learning, providing the first evidence that basal MAPK expression relates to functional outcomes following exposure to a risk factor for schizophrenia. On the basis of previous research, we believe that altered MAPK expression may be reflective of NMDA receptor dysfunction, however additional research is needed to explore whether MAPK may be independently contributing to pathology (Deane, Potemkin, & Ward, 2021).…”

Section: Sensitivity To Action-outcome Contingencies and The Mitogen ...mentioning

confidence: 99%

“…Substantial research has found that mid‐gestation polyIC exposure in rats (gestational day [GD] 15) induces a range of positive, negative, and cognitive phenotypes in conjunction with neurobiological changes analogous to those observed in schizophrenia (Haddad et al, 2020). Early and late rat models (GD10 and GD18/19) are also being used to understand the gestational window of vulnerability to this risk factor, however investigations are preliminary (da Silveira et al, 2017; Deane, Potemkin, & Ward, 2021; Hao et al, 2019; Rahman et al, 2020). Overall, the MIA model exhibits high construct, face, and predictive validity (Haddad et al, 2020), and when used in combination with an array of operant analyses, we have found it to provide powerful insight into the functional impairment and pathophysiology of schizophrenia.…”

Section: Schizophrenia and The Maternal Immune Activation (Mia) Modelmentioning

confidence: 99%

The instrumental role of operant paradigms in translational psychiatric research: Insights from a maternal immune activation model of schizophrenia risk

Deane

Ward

2022

J Exper Analysis Behavior

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Rigorous behavioral analysis is essential to the translation of research conducted using animal models of neuropsychiatric disease. Here we discuss the use of operant paradigms within our lab as a powerful approach for exploring the biobehavioral bases of disease in the maternal immune activation rat model of schizophrenia. We have investigated a range of disease features in schizophrenia including abnormal perception of time, cognition, learning, motivation, and internal state (psychosis), providing complex insights into brain and behavior. Beyond simple phenotyping, implementing sophisticated operant procedures has been effective in delineating aspects of pathological behavior, identifying interacting pathologies, and isolating contributing mechanisms of disease. We provide comment on the strengths of operant techniques to support high‐quality behavioral investigations in fundamental neuropsychiatric research.

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Mitogen-activated protein kinase (MAPK) signalling corresponds with distinct behavioural profiles in a rat model of maternal immune activation

Cited by 9 publications

References 40 publications

Bioinformatics analysis of long non-coding RNA-associated competing endogenous RNA network in schizophrenia

Bioinformatics analysis of long non-coding RNA-associated competing endogenous RNA network in schizophrenia

Resveratrol Attenuates the Proliferation of Prostatic Stromal Cells in Benign Prostatic Hyperplasia by Regulating Cell Cycle Progression, Apoptosis, Signaling Pathways, BPH Markers, and NF-κB Activity

The instrumental role of operant paradigms in translational psychiatric research: Insights from a maternal immune activation model of schizophrenia risk

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