Ppm1f is regulated by stress and associated with anxiety and depression
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ABSTRACT:
PROVIDER: PRJNA390645 | ENA |
REPOSITORIES: ENA
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Project description:Despite studies providing insight into the neurobiology of chronic stress, depression and anxiety, long noncoding RNA (lncRNA)-mediated mechanisms underlying the common and distinct pathophysiology of these stress-induced disorders remain nonconclusive. In a previous study, we used the chronic mild stress paradigm to separate depression-susceptible, anxiety-susceptible and insusceptible rat subpopulations. In the current study, lncRNA and messenger RNA (mRNA) expression was comparatively profiled in the hippocampus of the three stress groups using microarray technology. Groupwise comparisons identified distinct sets of lncRNAs and mRNAs associated with the three different behavioral phenotypes of the stressed rats. To investigate the regulatory roles of the dysregulated lncRNAs upon mRNA expression, correlations between the differential lncRNAs and mRNAs were first analyzed by combined use of weighted gene coexpression network analysis and ceRNA theory-based methods. Subsequent functional analysis of strongly correlated mRNAs indicated that the dysregulated lncRNAs were involved in various biological pathways and processes to specifically induce rat susceptibility or resiliency to depression or anxiety. Further intersectional analysis of phenotype-associated and drug-associated lncRNA-mRNA networks and subnetworks assisted in identifying 16 hub lncRNAs as potential targets of anti-depression/anxiety drugs. Collectively, our study established the molecular basis for understanding the similarities and differences in pathophysiological mechanisms underlying stress-induced depression or anxiety and stress resiliency, revealing several important lncRNAs that represent potentially new therapeutic drug targets for depression and anxiety disorders.
2020-08-21 | GSE156580 | GEO
Project description:Emerging evidence has shown that noncoding RNAs, particularly microRNAs (miRNAs), contribute to the pathogenesis of mood and anxiety disorders, although the molecular mechanisms are poorly understood. Here we show altered levels of miR-17-92 in adult hippocampal neural progenitors have a significant impact in neurogenesis and anxiety- and depression-related behaviors in mice. miR-17-92 deletion in adult neural progenitors causes a decrease, while its overexpression an increase of neurogenesis in the dentate gyrus, through regulating genes in the glucocorticoid pathway, especially serum- and glucocorticoid-inducible protein kinase-1 (Sgk1). miR-17-92 knockout mice show anxiety- and depression-like behaviors, whereas miR-17-92 overexpressing mice exhibit anxiolytic and antidepression-like behaviors. Furthermore, we show that miR-17-92 expression in the adult mouse hippocampus responds to chronic stress, and miR-17-92 rescues proliferation defects, induced by corticosterone, in hippocampal neural progenitors. Our study uncovers a crucial role for miR-17-92 in adult neural progenitors to regulate neurogenesis and anxiety- and depression-like behaviors.
2016-12-09 | GSE83636 | GEO
Project description:Neuropathic pain is a complex chronic condition, characterized by a wide range of sensory, cognitive, and affective symptoms. Indeed, a large percentage of neuropathic pain patients are also afflicted with depression and anxiety disorders -- a pattern that is reliably replicated in animal models. Mounting evidence from clinical and preclinical studies indicates that chronic pain corresponds with adaptations in several brain networks involved in mood, motivation, and reward. Chronic stress is also a major determinant for depression. However, whether chronic pain and chronic stress affect similar mechanisms, and whether chronic pain can affect gene expression patterns known to be involved in depression, remains poorly understood. We employed the spared nerve injury model (SNI) of neuropathic pain in adult C57BL\6 mice and performed next-generation RNA-sequencing in order to monitor changes in gene expression in three brain regions known to be implicated in the pathophysiology of depression and in the modulation of pain: the nucleus accumbens (NAc), the medial prefrontal cortex (mPFC), and the periaqueductal grey (PAG). We observed mostly unique transcriptome profiles across the three brain regions but found common intracellular signal transduction pathways and biological functions were affected. A large amount of genes showing SNI-induced altered expression have been implicated in depression, anxiety, or chronic pain. In addition, we identified genes that are similarly regulated in a murine model of depression: chronic unpredictable stress. Our study provides the first unbiased characterization of neuropathic pain-induced long-term gene expression changes in three distinct brain regions, and presents evidence that neuropathic pain affects the expression of several genes that are also regulated by chronic stress.
2017-09-06 | GSE91396 | GEO
Project description:Acute stress-induced anxiety is an important way for animals to avoid danger. However, neural and molecular mechanisms that underlie control of anxiety behavior are largely elusive. Here, we find acute physical stress activates a large number of neurons in the primary somatosensory cortex, trunk region (S1Tr). Single-cell sequencing reveals the S1Tr c-fos positive neurons activated by acute stress are largely GABAergic somatostatin (Sst) neurons. These S1TrSst neurons activated by acute stress showed desensitization during subsequent anxiety-like behavior tests. Selective inhibition or apoptosis of S1TrSst neurons mimics acute stress effects to induce anxiety. In contrast, selective activation of S1TrSst neurons reduced acute stress-induced anxiety. Furthermore, we demonstrate that S1TrSst cells receive inputs from the secondary auditory cortex, dorsal area (AUD) GABAergic neurons to modulate acute stress-induced anxiety. Finally, from the results of spatial transcriptome sequencing and precise projection-specificity Pde4b protein knockdown strategy, we show that acute stress reduces Pde4b-regulated cyclic adenosine monophosphate (cAMP) signaling pathway activity in the AUDGABA-S1TrSst projections and resulting in a hypoactivity of S1TrSst neurons during subsequent behavioral tests. Our study unveils a neural and molecular mechanism for acute stress-elicited anxiety and affords a theoretical basis for clinical treatment of anxiety disorders.
2025-01-02 | GSE285495 | GEO
Project description:Acute stress-induced anxiety is an important way for animals to avoid danger. However, neural and molecular mechanisms that underlie control of anxiety behavior are largely elusive. Here, we find acute physical stress activates a large number of neurons in the primary somatosensory cortex, trunk region (S1Tr). Single-cell sequencing reveals the S1Tr c-fos positive neurons activated by acute stress are largely GABAergic somatostatin (Sst) neurons. These S1TrSst neurons activated by acute stress showed desensitization during subsequent anxiety-like behavior tests. Selective inhibition or apoptosis of S1TrSst neurons mimics acute stress effects to induce anxiety. In contrast, selective activation of S1TrSst neurons reduced acute stress-induced anxiety. Furthermore, we demonstrate that S1TrSst cells receive inputs from the secondary auditory cortex, dorsal area (AUD) GABAergic neurons to modulate acute stress-induced anxiety. Finally, from the results of spatial transcriptome sequencing and precise projection-specificity Pde4b protein knockdown strategy, we show that acute stress reduces Pde4b-regulated cyclic adenosine monophosphate (cAMP) signaling pathway activity in the AUDGABA-S1TrSst projections and resulting in a hypoactivity of S1TrSst neurons during subsequent behavioral tests. Our study unveils a neural and molecular mechanism for acute stress-elicited anxiety and affords a theoretical basis for clinical treatment of anxiety disorders.
2025-01-03 | GSE285650 | GEO
Project description:Ppm1f regulation in the amygdala after acute stress immobilization
2017-06-16 | GSE100084 | GEO
Project description:Ppm1f regulation in the medial prefrontal cortex (mPFC) after acute stress immobilization
2017-06-16 | GSE100085 | GEO
Project description:MAP kinase signaling has been implicated in brain development, long-term memory, and the response to antidepressants. Inducible Braf knockout mice enabled us to unravel a new role of neuronal MAPK signaling for emotional behavior. Braf mice that were induced during adulthood showed normal anxiety but increased depression-like behavior, in accordance with pharmacological findings. In contrast, the inactivation of Braf in the juvenile brain leads to normal depression-like behavior but decreased anxiety in adults. In these mutants we found no alteration of GABAergic neurotransmission but reduced neuronal arborization in the dentate gyrus. Analysis of gene expression in the hippocampus revealed nine downregulated MAPK target genes that represent candidates to cause the mutant phenotype. Our results reveal the differential function of MAPK signaling in juvenile and adult life phases and emphasize the early postnatal period as critical for the determination of anxiety in adults. Moreover, these results validate inducible gene inactivation as new valuable approach, allowing to discriminate between gene function in the adult and the developing postnatal brain. Five male Braf-cko, six male homozygous Braf-flox littermates, six male heterozygous CamkII-Cre, and six male wildtype littermates were killed with CO2, the complete hippocampal tissue was prepared, and total RNA was extracted with the Trizol protocol. The integrity and quality of the RNA samples were analyzed with an RNA electrophoresis chip (RNA 6000 Nano Kit, Agilent, Boeblingen, Germany). RNA samples of high integrity and quality (RIN ≥ 7.5) were further processed with the TotalPrep RNA Amplification Kit (Ambion, Austin, TX, USA) and hybridized onto MouseWG-6 v1.1 Expression Bead-Chips (Illumina, San Diego, CA, USA) following manufacturer’s instructions. Data were analyzed using the software R (used packages: beadarray, limma, and vsn).
2012-04-18 | E-GEOD-33618 | biostudies-arrayexpress
Project description:MAP kinase signaling has been implicated in brain development, long-term memory, and the response to antidepressants. Inducible Braf knockout mice enabled us to unravel a new role of neuronal MAPK signaling for emotional behavior. Braf mice that were induced during adulthood showed normal anxiety but increased depression-like behavior, in accordance with pharmacological findings. In contrast, the inactivation of Braf in the juvenile brain leads to normal depression-like behavior but decreased anxiety in adults. In these mutants we found no alteration of GABAergic neurotransmission but reduced neuronal arborization in the dentate gyrus. Analysis of gene expression in the hippocampus revealed nine downregulated MAPK target genes that represent candidates to cause the mutant phenotype. Our results reveal the differential function of MAPK signaling in juvenile and adult life phases and emphasize the early postnatal period as critical for the determination of anxiety in adults. Moreover, these results validate inducible gene inactivation as new valuable approach, allowing to discriminate between gene function in the adult and the developing postnatal brain.
2012-04-19 | GSE33618 | GEO
Project description:The molecular etiology of invididual differences in complex behavior traits and susceptibility to psychiatric illness remains incomplete. Using an unbiased genetic approach in a mouse model, Quantitative Trait Loci (QTL) influencing anxiety-like behaviors and beta-carboline-induced seizure vulnerability have been mapped to the distal portion of mouse chromosome 10 and an interval specific congenic strain (ISCS; A.B6chr10; 66 cM to telomere) was developed. This A.B6chr10 strain facilitated defining the behavioral influences of this region as well as gene expression profiling to identify candidate gene(s) underlying this QTL. By microarray studies, an unsuspected E3 Ubiquitin Ligase, Ring Finger 41 (Rnf41 / Neuregulin Receptor Degrading Protein1; Nrdp1) was differentially expressed in the region of interest, comparing the hippocampi of A/J vs A.B6chr10 mice as well as A/J vs B6 mice. By RT-PCR, Rnf41 expression levels were significantly increased 1.5 and 1.3-fold in the hippocampi of C57BL6/J and A.B6chr10 mice compared to A/J mice, respectively. In addition, protein levels of Rnf41 were increased in hippocampi of B6 mice compared to A/J mice across postnatal development with a 5.5-fold difference at P56. Among LxS recombinant inbred mice (N=33), Rnf41 hippocampal mRNA expression levels were significantly correlated with open field behavior (r= .454, p=.0073). Re-analyzing a microarray database of human post-mortem prefrontal cortex (Brodmann’s Area 46/10), RNF41 mRNA expression levels were reduced significantly in patients with major depression and bipolar disorder compared to unaffected controls. Overall, Rnf41 is a pleiotropic candidate gene for anxiety-like behaviors, depression, and vulnerability to seizures. RNF41 and its binding partners provide novel etiological pathways for influencing behavior, highlighting a potential role for the ubiquitin proteasome system in psychiatric illness. Keywords: strain difference, genetic variation
2008-06-30 | GSE8641 | GEO