scholarly journals Role of the habenulo-interpeduncular system in the neurodevelopmental basis of susceptibility and resilience to stress-induced anxiety

2022 ◽  
Author(s):  
Malalaniaina Rakotobe ◽  
Niels Fjerdingstad ◽  
Nuria Ruiz-Reig ◽  
Thomas Lamonerie ◽  
Fabien D'Autréaux
Keyword(s):  
Stress Response ◽  
Brain Development ◽  
Chronic Stress ◽  
Environmental Stressors ◽  
Critical Node ◽  
Sensitive Periods ◽  
Early Stress ◽  
Effects Of Stress

Abstract Experiencing stress during sensitive periods of brain development has a major impact on how individuals cope with later stress. Although many become more prone to develop anxiety or depression, some appear resilient. The mechanisms underlying these differences are unknown. Key answers may lie in how genetic and environmental stressors interact to shape the circuits controlling emotions. Here we studied the role of the habenulo-interpeducuncular system (HIPS), a critical node of reward circuits, in early stress-induced anxiety. We found that a subcircuit of this system, characterized by Otx2 expression, is particularly responsive to chronic stress during puberty, which induces HIPS hypersensitivity to later stress and susceptibility to develop anxiety. We further show that Otx2 deletion restricted to the HIPS counteracts these effects of stress. Together, these results demonstrate that Otx2 and stress interact, around puberty, to shape the HIPS stress-response, revealed here as a key modulator of susceptibility/resilience to develop anxiety.

scholarly journals Central role of the habenulo-interpeduncular system in the neurodevelopmental basis of susceptibility and resilience to anxiety

2021 ◽  
Author(s):  
Malalaniaina Rakotobe ◽  
Niels Fjerdingstad ◽  
Nuria Ruiz-Reig ◽  
Thomas Lamonerie ◽  
Fabien D'Autréaux
Keyword(s):  
Stress Response ◽  
Brain Development ◽  
Chronic Stress ◽  
Environmental Stressors ◽  
Critical Node ◽  
Sensitive Periods ◽  
Early Stress ◽  
Effects Of Stress

Abstract Experiencing stress during sensitive periods of brain development has a major impact on how individuals cope with later stress. Although many become more prone to develop anxiety or depression, some appear resilient. The mechanisms underlying these differences are unknown. Key answers may lie in how genetic and environmental stressors interact to shape the circuits controlling emotions. Here we studied the role of the habenulo-interpeducuncular system (HIPS), a critical node of reward circuits, in early stress-induced anxiety. We found that a subcircuit of this system, characterized by Otx2 expression, is particularly responsive to chronic stress during puberty, which induces HIPS hypersensitivity to later stress and susceptibility to develop anxiety. We further show that Otx2 deletion restricted to the HIPS counteracts these effects of stress. Together, these results demonstrate that Otx2 and stress interact, around puberty, to shape the HIPS stress-response, revealed here as a key modulator of susceptibility/resilience to develop anxiety.

scholarly journals Role of the habenulo-interpeduncular system in the neurodevelopmental basis of susceptibility and resilience to stressinduced anxiety

2022 ◽  
Author(s):  
Malalaniaina Rakotobe ◽  
Niels Fjerdingstad ◽  
Nuria Ruiz-Reig ◽  
Thomas Lamonerie ◽  
Fabien D'Autréaux
Keyword(s):  
Stress Response ◽  
Brain Development ◽  
Chronic Stress ◽  
Environmental Stressors ◽  
Critical Node ◽  
Sensitive Periods ◽  
Early Stress ◽  
Effects Of Stress

Abstract Experiencing stress during sensitive periods of brain development has a major impact on how individuals cope with later stress. Although many become more prone to develop anxiety or depression, some appear resilient. The mechanisms underlying these differences are unknown. Key answers may lie in how genetic and environmental stressors interact to shape the circuits controlling emotions. Here we studied the role of the habenulo-interpeducuncular system (HIPS), a critical node of reward circuits, in early stress-induced anxiety. We found that a subcircuit of this system, characterized by Otx2 expression, is particularly responsive to chronic stress during puberty, which induces HIPS hypersensitivity to later stress and susceptibility to develop anxiety. We further show that Otx2 deletion restricted to the HIPS counteracts these effects of stress. Together, these results demonstrate that Otx2 and stress interact, around puberty, to shape the HIPS stress-response, revealed here as a key modulator of susceptibility/resilience to develop anxiety.

scholarly journals Flavonoids Ameliorate Stress-Induced Depression by Preventing NLRP3 Inflammasome Priming

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1231-1231
Author(s):  
Giulio Pasinetti
Keyword(s):  
Mrna Expression ◽  
Chronic Stress ◽  
Nlrp3 Inflammasome ◽  
Signaling Cascades ◽  
Dietary Polyphenols ◽  
Funding Sources ◽  
Glycation End Products ◽  
Molecular Patterns

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.

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