Spatial learning and long‐term memory impairments in RasGrf1 KO, Pttg1 KO, and double KO mice

Manyes, Lara; Holst, Sarah; Lozano, Manuel; Santos, Eugenio; Fernández‐Medarde, Alberto

doi:10.1002/brb3.1089

Cited by 10 publications

(7 citation statements)

References 31 publications

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“…Functional analysis has demonstrated that this protein stimulates the dissociation of GDP from RAS protein. The Ras-GEF signaling pathway may be important for long-term memory [39]. A recent study in a mouse model of depression suggests that altering this gene's expression may be an essential link in the mood-regulating effects of drugs [40].…”

Section: Discussionmentioning

confidence: 99%

Expression Biomarkers of Pharmacological Treatment Outcomes in Women with Unipolar and Bipolar Depression

et al. 2021

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Introduction This study aimed to find the expression biomarkers of pharmacological treatment response in a naturalistic hospital setting. Through gene expression profiling, we were able to find differentially-expressed genes (DEGs) in unipolar (UD) and bipolar (BD) depressed women. Methods We performed gene expression profiling in hospitalized women with unipolar (n=24) and bipolar depression (n=32) who achieved clinical improvement after pharmacological treatment (without any restriction). To identify DEGs in peripheral blood mononuclear cells (PBMCs), we used the SurePrint G3 Microarray and GeneSpring software. Results After pharmacological treatment, UD and BD varied in the number of regulated genes and ontological pathways. Also, the pathways of neurogenesis and synaptic transmission were significantly up-regulated. Our research focused on DEGs with a minimum fold change (FC) of more than 2. For both types of depression, 2 up-regulated genes, OPRM1 and CELF4 (p=0.013), were significantly associated with treatment response (defined as a 50% reduction on the Hamilton Depression Rating Scale [HDRS]). We also uncovered the SHANK3 (p=0.001) gene that is unique for UD and found that the RASGRF1 (p=0.010) gene may be a potential specific biomarker of treatment response for BD. Conclusion Based on transcriptomic profiling, we identified potential expression biomarkers of treatment outcomes for UD and BD. We also proved that the Ras-GEF pathway associated with long-term memory, female stress response, and treatment response modulation in animal studies impacts treatment efficacy in patients with BD. Further studies focused on the outlined genes may help provide predictive markers of treatment outcomes in UD and BD.

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Section: Discussionmentioning

confidence: 99%

Expression Biomarkers of Pharmacological Treatment Outcomes in Women with Unipolar and Bipolar Depression

et al. 2021

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“…Ccne1, ccne1 and ccnb1 belonged to the cyclin family, and were essential for the control of the cell cycle (Sauer et al, 1995). The other genes, such as ppp1cb and pttg1, played vital roles in chromosome stability (Barker et al, 1994;Manyes et al, 2018).…”

Section: Resultsmentioning

confidence: 99%

Comprehensive analysis of miRNA-mRNA/lncRNA during gonadal development of triploid female rainbow trout (Oncorhynchus mykiss)

et al. 2021

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Background: Chromosomal ploidy manipulation is one of the means to create excellent germplasm. Triploid sh could provide an ideal sterile model for the mechanism research of abnormality in meiosis. The complete understanding of the coding and noncoding RNAs regulating sterility caused by meiosis abnormality is still not well understood.Results: By high-throughput sequencing, we compared the expression pro les of gonadal mRNA, long non-coding RNA (lncRNA), and microRNA (miRNA) at different developmental stages [65 days post fertilisation (dpf), 180 dpf, and 600 dpf] between the diploid (XX) and triploid (XXX) female rainbow trout. A majority of differentially expressed (DE) RNAs were identi ed, and 22 DE mRNAs related to oocyte meiosis and homologous recombination were characterized. The predicted miRNA-mRNA/lncRNA networks of 3 developmental stages were constructed based on the target pairs of DE lncRNA-miRNA and DE mRNA-miRNA. According to the networks, meiosis-related gene of ccne1 was targeted by dre-miR-15a-5p_R+1, and 6 targeted DE lncRNAs were identi ed. Also, RT-qPCR was performed to validate the credibility of the network.Conclusions: This study explored the potential interplay between coding and noncoding RNAs during the gonadal development of polyploid sh. It provides full insights into polyploidy-associated effects on fertility of sh. These differentially expressed coding and noncoding RNAs provide a novel resource for studying genome diversity of polyploid induction.

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“…A further fourteen genes ( 1700048O20Rik , Abdh1 , Adat2 , Gvin1 , Irgm2 , Itgb3bp , Kbtbd11 , Lacc1 , Nmrk1 , Pyurf , Slc25a37 , Slc39a2 , Stxbp2 , Zfp125 ) were commonly regulated between hippocampus and cerebellum but were not hypothalamic cPRGs. The cPRG transcripts most dramatically down-regulated (2-fold or more) are Pttg1 , a transcriptional activator associated with development [22]; Mid1 , implicated in structural brain defects, Huntington’s and Alzheimer’s pathology [23], 4833420G17Rik , a predicted protein (orf) of unknown function, and Pisd-ps3 , phosphatidylserine decarboxylase pseudogene 3, regulated in aging [24]. Mrpl20 and Xaf1 are genes encoding known proteins of unknown function in the nervous system.…”

Section: Resultsmentioning

confidence: 99%

Relationship between constitutive and acute gene regulation, and physiological and behavioral responses, mediated by the neuropeptide PACAP

Bakalar

Sweat

Drossel

et al. 2021

Preprint

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Since the advent of gene knockout technology in 1987, insight into the role(s) of neuropeptides in centrally- and peripherally-mediated physiological regulation has been gleaned by examining altered physiological functioning in mammals, predominantly mice, after genetic editing to produce animals deficient in neuropeptides or their cognate G-protein coupled receptors (GPCRs). These results have complemented experiments involving infusion of neuropeptide agonists or antagonists systemically or into specific brain regions. Effects of gene loss are typically interpreted as indicating that the peptide and its receptor(s) are required for the physiological or behavioral responses elicited in wild-type mice at the time of experimental examination. These interpretations presume that peptide/peptide receptor gene deletion affects only the expression of the peptide/receptor itself, and therefore impacts physiological events only at the time at which the experiment is conducted. A way to support real-time interpretations of neuropeptide gene knock-out is to demonstrate that the wild-type transcriptome, except for the deliberately deleted gene(s), in tissues of interest, is preserved in the knock-out mouse. Here, we show that there is a cohort of genes (constitutively PACAP regulated genes, or cPRGs) whose basal expression is affected by constitutive knock-out of the Adcyap1 gene in C57Bl6/N mice, and additional genes whose expression in response to physiological challenge, in adults, is altered or impaired in the absence of PACAP expression (acutely PACAP-regulated genes, or aPRGs). Distinguishing constitutive and acute transcriptomic effects of neuropeptide deficiency on physiological function and behavior in mice reveals alternative mechanisms of action, and changing functions of neuropeptides, throughout the lifespan.

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Spatial learning and long‐term memory impairments in RasGrf1 KO, Pttg1 KO, and double KO mice

Cited by 10 publications

References 31 publications

Expression Biomarkers of Pharmacological Treatment Outcomes in Women with Unipolar and Bipolar Depression

Expression Biomarkers of Pharmacological Treatment Outcomes in Women with Unipolar and Bipolar Depression

Comprehensive analysis of miRNA-mRNA/lncRNA during gonadal development of triploid female rainbow trout (Oncorhynchus mykiss)

Relationship between constitutive and acute gene regulation, and physiological and behavioral responses, mediated by the neuropeptide PACAP

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