scholarly journals Analysis of Differentially Expressed Genes in the Dentate Gyrus and Anterior Cingulate Cortex in a Mouse Model of Depression

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Yicong Wei ◽  
Keming Qi ◽  
Yi Yu ◽  
Wei Lu ◽  
Wei Xu ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Anterior Cingulate Cortex ◽  
Differentially Expressed Genes ◽  
Visual Learning ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Differentially Expressed ◽  
Psychiatric Disease ◽  
Mild Stress ◽  
Hub Genes

Major depressive disorder (MDD) is a prevalent, chronic, and relapse-prone psychiatric disease. However, the intermediate molecules resulting from stress and neurological impairment in different brain regions are still unclear. To clarify the pathological changes in the dentate gyrus (DG) and anterior cingulate cortex (ACC) regions of the MDD brain, which are the most closely related to the disease, we investigated the published microarray profile dataset GSE84183 to identify unpredictable chronic mild stress- (UCMS-) induced differentially expressed genes (DEGs) in the DG and ACC regions. Based on the DEG data, functional annotation, protein-protein interaction, and transcription factor (TF) analyses were performed. In this study, 1071 DEGs (679 upregulated and 392 downregulated) and 410 DEGs (222 upregulated and 188 downregulated) were identified in DG and ACC, respectively. The pathways and GO terms enriched by the DEGs in the DG, such as cell adhesion, proteolysis, ion transport, transmembrane transport, chemical synaptic transmission, immune system processes, response to lipopolysaccharide, and nervous system development, may reveal the molecular mechanism of MDD. However, the DEGs in the ACC involved metabolic processes, proteolysis, visual learning, DNA methylation, innate immune responses, cell migration, and circadian rhythm. Sixteen hub genes in the DG (Fn1, Col1a1, Anxa1, Penk, Ptgs2, Cdh1, Timp1, Vim, Rpl30, Rps21, Dntt, Ptk2b, Jun, Avp, Slit1, and Sema5a) were identified. Eight hub genes in the ACC (Prkcg, Grin1, Syngap1, Rrp9, Grwd1, Pik3r1, Hnrnpc, and Prpf40a) were identified. In addition, eleven TFs (Chd2, Zmiz1, Myb, Etv4, Rela, Tcf4, Tcf12, Chd1, Mef2a, Ubtf, and Mxi1) were predicted to regulate more than two of these hub genes. The expression levels of ten randomly selected hub genes that were specifically differentially expressed in the MDD-like animal model were verified in the corresponding regions in the human brain. These hub genes and TFs may be regarded as potential targets for future MDD treatment strategies, thus aiding in the development of new therapeutic approaches to MDD.

scholarly journals Depressive-like States Heighten the Aversion to Painful Stimuli in a Rat Model of Comorbid Chronic Pain and Depression

2012 ◽  
Vol 117 (3) ◽  
pp. 613-625 ◽  
Author(s):  
Lidia Bravo ◽  
Juan Antonio Mico ◽  
Raquel Rey-Brea ◽  
Beatriz Pérez-Nievas ◽  
Juan Carlos Leza ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Anterior Cingulate Cortex ◽  
Rat Model ◽  
Chronic Mild Stress ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Mild Stress ◽  
Sham Control ◽  
Neuronal Density ◽  
Extracellular Signal

Background Chronic pain and depression are two complex states with sensory/somatic and emotional components, and they may mutually exacerbate one another in conditions of comorbidity, leading to a poorer prognosis. Methods The authors have evaluated the sensory and emotional components in a rat model combining chronic constriction injury (CCI, a model of chronic neuropathic pain) with unpredictable chronic mild stress (CMS, an experimental model of depression). In addition, the phosphorylation/activation of the extracellular signal-regulated kinases 1 and 2 and neuronal density was also evaluated in the anterior cingulate cortex. Four groups were tested: sham-control, sham-CMS, CCI-control, and CCI-CMS. Results CMS selectively heightens aversion to painful experiences in animals subjected to CCI, as measured in the place escape/avoidance test at 20, 25, and 30 min (CCI-CMS (mean±SEM): 75.68±3.32, 66.75±4.70, 77.54±3.60 vs. CCI-control: 44.66±6.07, 43.17±6.92, 52.83±5.92, respectively), in conjunction with an increase in the accumulation of phosphorylation/activation of the extracellular signal-regulated kinases (CCI-CMS: 4.17±0.52 vs. sham-control: 0.96±0.05) and a decrease in neuronal density in the anterior cingulate cortex. In contrast, chronic pain did not exacerbate the characteristic profile of depression (anhedonia and behavioral despair) in rats subjected to CMS. Furthermore, depression enhances the perception of some specific modalities of sensorial pain such as cold allodynia but has no influence on mechanical threshold. Conclusions These findings support the theory that depression leads to emotional dysfunction in the interpretation of pain in patients suffering chronic pain. In addition, combined animal models of pain-depression may provide a valuable tool to study the comorbidity of pain and depression.

scholarly journals Chronic stress exacerbates acute stress-induced neuronal activation in the anterior cingulate cortex and ventral hippocampus that correlates with behavioral deficits in mice

2020 ◽  
Author(s):  
Corey Fee ◽  
Thomas Prevot ◽  
Keith Misquitta ◽  
Mounira Banasr ◽  
Etienne Sibille
Keyword(s):  
Stress Response ◽  
Anterior Cingulate Cortex ◽  
Chronic Stress ◽  
Acute Stress ◽  
Cingulate Cortex ◽  
Brain Regions ◽  
Anterior Cingulate ◽  
Mild Stress ◽  
Neuronal Activation ◽  
Behavioral Deficits

AbstractAltered activity of corticolimbic brain regions is a hallmark of stress-related illnesses, including mood disorders, neurodegenerative diseases, and substance abuse disorders. Acute stress adaptively recruits brain region-specific functions for coping, while sustained activation under chronic stress may overwhelm feedback mechanisms and lead to pathological cellular and behavioral responses. The neural mechanisms underlying dysregulated stress response and how they contribute to behavioral deficits are poorly characterized. Here, we tested whether prior exposure to chronic restraint stress (CRS) or unpredictable chronic mild stress (UCMS) in mice could alter neuronal response to acute stress and whether these changes are associated with chronic stress-induced behavioral deficits. More specifically, we assessed neuronal activation indexed by c-Fos+ cell counts in 24 stress- and mood-related brain regions, and determined if changes in acute stress-induced neuronal activation were linked to chronic stress-induced behavioral impairments. Results indicated that CRS and UCMS led to convergent physiological and anxiety-like deficits, whereas cognition was impaired only in UCMS mice. CRS and UCMS exposure exacerbated neuronal activation in response to an acute stressor in anterior cingulate cortex (ACC) area 24b and ventral hippocampal (vHPC) CA1, CA3, and subiculum. In dysregulated brain regions, levels of neuronal activation were positively correlated with principal components capturing variance across widespread behavioral alterations relevant to stress-related disorders. Our data supports an association between a dysregulated stress response, altered corticolimbic excitation/inhibition balance, and the expression of maladaptive behaviors.HighlightsChronic stress models produce variable profiles of physiological deficits, anxiety-like behavior, and impaired cognitionAcute stress-induced activation of ACC A24b & vHPC is exacerbated by prior chronic stress exposureIn regions dysregulated by chronic stress, altered neuronal activation is positively correlated with behavioral deficits

EXPANSION OF THE ANTERIOR CINGULATE CORTEX IN CHILDREN WITH LEARNING DISABILITY OF UNKNOWN AETIOLOGY

2006 ◽  
Vol 37 (S 1) ◽  
Author(s):  
M Mannerkoski ◽  
H Heiskala ◽  
K Van Leemput ◽  
L Åberg ◽  
R Raininko ◽  
...  
Keyword(s):  
Learning Disability ◽  
Anterior Cingulate Cortex ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Unknown Aetiology
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