scholarly journals Role of the modulation of Nkb pathway in chronic stress induced changes in the BNST and consequences on the anxiety behavior

IBRO Reports ◽  
2019 ◽  
Vol 6 ◽  
pp. S78
Author(s):  
Aurelie Menigoz ◽  
Donald Rainnie ◽  
Katie Barrett ◽  
Megan Jiang ◽  
Larry Young
2020 ◽  
Vol 10 (11) ◽  
pp. 833
Author(s):  
Swati Maitra ◽  
Nitin Khandelwal ◽  
Scherazad Kootar ◽  
Pooja Sant ◽  
Salil S. Pathak ◽  
...  

Depression, anxiety and related mood disorders are major psychiatric illnesses worldwide, and chronic stress appears to be one of the primary underlying causes. Therapeutics to treat these debilitating disorders without a relapse are limited due to the incomplete molecular understanding of their etiopathology. In addition to the well-studied genetic component, research in the past two decades has implicated diverse epigenetic mechanisms in mediating the negative effects of chronic stressful events on neural circuits. This includes the cognitive circuitry, where the dynamic hippocampal dentate gyrus (DG) neurogenesis gets affected in depression and related affective disorders. Most of these epigenetic studies have focused on the impact of acetylation/deacetylation and methylation of several histone lysine residues on neural gene expression. However, there is a dearth of investigation into the role of demethylation of these lysine residues in chronic stress-induced changes in neurogenesis that results in altered behaviour. Here, using the chronic social defeat stress (CSDS) paradigm to induce depression and anxiety in C57BL/6 mice and ex vivo DG neural stem/progenitor cell (NSCs/NPCs) culture we show the role of the members of the JMJD2/KDM4 family of histone lysine demethylases (KDMs) in mediating stress-induced changes in DG neurogenesis and mood disorders. The study suggests a critical role of JMJD2D in DG neurogenesis. Altered enrichment of JMJD2D on the promoters of Id2 (inhibitor of differentiation 2) and Sox2 (SRY-Box Transcription Factor 2) was observed during proliferation and differentiation of NSCs/NPCs obtained from the DG. This would affect the demethylation of repressive epigenetic mark H3K9, thus activating or repressing these and possibly other genes involved in regulating proliferation and differentiation of DG NSCs/NPCs. Treatment of the NSCs/NPCs culture with Dimethyloxallyl Glycine (DMOG), an inhibitor of JMJDs, led to attenuation in their proliferation capacity. Additionally, systemic administration of DMOG in mice for 10 days induced depression-like and anxiety-like phenotype without any stress exposure.


2013 ◽  
Vol 75 ◽  
pp. 426-436 ◽  
Author(s):  
Sjoukje D. Kuipers ◽  
Andrea Trentani ◽  
Eddy A. van der Zee ◽  
Johan A. den Boer

2017 ◽  
Vol 8 (1) ◽  
pp. 15-20
Author(s):  
Giridhari Pal ◽  
Vishwajeet Rohil ◽  
Razi Akhtar ◽  
Tapan Behl ◽  
Sudha Bharati ◽  
...  

Background: Stress is the psycho-physiologic reaction of the body to diverse stimuli including emotional or physical stimuli that imbalance the homeostasis and is also known to trigger various stress markers. Despite the stressors of different types, chronic stress in particular, is known to influence the physiological milieu and breakdown of adaptive mechanisms consequently aggravating the morbid states.  Aims and Objectives: The present study was designed to evaluate the modulatory role of stress marker by N-nitro-L-arginine-methyl ester (L-NAME) and L-Ascorbic acid (L-AA) in experimental model of chronic restraint stress (RSx21) in Wistar rats.Materials and Methods: MDA and GSH levels were determined by the method of Okhawa et al 1979 and Ellman 1959 respectively, the SOD and catalase levels were estimated by the method of Nandi and Chatterjee 1988 and Aebi 1984 respectively.Results: Results from our study reveal the significant enhancement of malondialdehyde (MDA) level while significant attenuation of superoxide dismutase (SOD), reduced glutathione (GSH) and catalase levels in chronic stress group compared with vehicle (non-stress) group. The MDA level was found to be increased by L-NAME (10 and 50 mg/kg) in chronic restraint (RSx21) induced rats as compared to vehicle treated RS group. Antioxidant L-AA (100 and 200 mg/kg) significantly reduced MDA level in chronic stress situation. However, L-NAME and L-Ascorbic Acid were found to cause an increase in level of plasma SOD, GSH and catalase when compared with vehicle treated RS group. On the other hand, L-AA (100 and 200 mg/kg) reversed these RS induced changes in these oxidative parameters.Conclusions: Hence, results from the study underlined the intricate role of antioxidants as evidenced by reversal of oxidative stress markers that command a vital role in the development of morbid condition.Asian Journal of Medical Sciences Vol.8(1) 2017 15-20


Author(s):  
L. T. Germinario

Understanding the role of metal cluster composition in determining catalytic selectivity and activity is of major interest in heterogeneous catalysis. The electron microscope is well established as a powerful tool for ultrastructural and compositional characterization of support and catalyst. Because the spatial resolution of x-ray microanalysis is defined by the smallest beam diameter into which the required number of electrons can be focused, the dedicated STEM with FEG is the instrument of choice. The main sources of errors in energy dispersive x-ray analysis (EDS) are: (1) beam-induced changes in specimen composition, (2) specimen drift, (3) instrumental factors which produce background radiation, and (4) basic statistical limitations which result in the detection of a finite number of x-ray photons. Digital beam techniques have been described for supported single-element metal clusters with spatial resolutions of about 10 nm. However, the detection of spurious characteristic x-rays away from catalyst particles produced images requiring several image processing steps.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1231-1231
Author(s):  
Giulio Pasinetti

Abstract Objectives Chronic stress activates danger-associated molecular patterns (DAMPs), stimulating the NLRP3 inflammasome. NLRP3 activation triggers the release of pro-inflammatory cytokine IL-1β. The activity of the NLRP3 inflammasome propagates pro-inflammatory signaling cascades implicated in the onset of depression. Our previous studies show that polyphenolic compounds were found to ameliorate stress induced depression in mouse models. However, the relevant mechanism has not been identified. This study examined the effect of administering polyphenols on DAMP signaling in enriched mice microglia. Methods This study examined the effect of administering polyphenols on DAMP signaling in mice microglia. To recapitulate stress-induced depression, mice underwent chronic unpredictable stress (CUS). Microglia were isolated at various time points throughout the CUS protocol. We also assessed long-term persistent changes after CUS and susceptibility to subthreshold unpredictable stress (US) re-exposure. Results Interestingly, the development of US – induced depression and anxiety depended upon a previous exposure to CUS. We found that CUS caused robust upregulation of IL-1β mRNA in enriched microglia, an effect that persists for up to 4 weeks following CUS exposure. Following the subthreshold US re-exposure, we observed the upregulation of pro- IL-1β as well as pro-receptor for advanced glycation end products (RAGE). Toll-like receptor 4 (TLR-4) was not. We also observed an increase in RAGE mRNA expression when mice were exposed to US prior to the start of the CUS paradigm. Importantly, a primary exposure to US, was sufficient to increase RAGE mRNA expression. We found that polyphenol administration significantly improved CUS-induced depressive-like phenotypes and also reversed neuroinflammation in mice. Treatment with dietary flavonoids prevented upregulation of IL-1β, RAGE mRNA, which reflects the ability of polyphenols that may have begun following the primary exposure to US. Conclusions Taken all together, the results provide evidence of the role of dietary polyphenols in preventing persistent microglial activation, which has been shown to result in reduced long term vulnerability to depressive-like behaviors following expose to chronic stress. Funding Sources This study was supported by a P50 CARBON Center grant from the NCCIH/ODS.


2021 ◽  
Vol 98 ◽  
pp. 107832
Author(s):  
Hirva K. Bhatt ◽  
Dana Song ◽  
Gyen Musgrave ◽  
P.S.S. Rao

2021 ◽  
Vol 22 (14) ◽  
pp. 7713
Author(s):  
Alyssa Tidmore ◽  
Sucharita M. Dutta ◽  
Arriyam S. Fesshaye ◽  
William K. Russell ◽  
Vania D. Duncan ◽  
...  

Exposure of rodents to <20 cGy Space Radiation (SR) impairs performance in several hippocampus-dependent cognitive tasks, including spatial memory. However, there is considerable inter-individual susceptibility to develop SR-induced spatial memory impairment. In this study, a robust label-free mass spectrometry (MS)-based unbiased proteomic profiling approach was used to characterize the composition of the hippocampal proteome in adult male Wistar rats exposed to 15 cGy of 1 GeV/n 48Ti and their sham counterparts. Unique protein signatures were identified in the hippocampal proteome of: (1) sham rats, (2) Ti-exposed rats, (3) Ti-exposed rats that had sham-like spatial memory performance, and (4) Ti-exposed rats that impaired spatial memory performance. Approximately 14% (159) of the proteins detected in hippocampal proteome of sham rats were not detected in the Ti-exposed rats. We explored the possibility that the loss of the Sham-only proteins may arise as a result of SR-induced changes in protein homeostasis. SR-exposure was associated with a switch towards increased pro-ubiquitination proteins from that seen in Sham. These data suggest that the role of the ubiquitin-proteome system as a determinant of SR-induced neurocognitive deficits needs to be more thoroughly investigated.


Sign in / Sign up

Export Citation Format

Share Document