scholarly journals Infralimbic BDNF signaling is necessary for the beneficial effects of extinction on set shifting in stressed rats

2021 ◽  
Author(s):  
Denisse Paredes ◽  
Anna R. Knippenberg ◽  
David A. Morilak
Keyword(s):  
Chronic Stress ◽  
Exposure Therapy ◽  
Neutralizing Antibody ◽  
Akt Signaling ◽  
Set Shifting ◽  
Major Depressive ◽  
Beneficial Effects ◽  
Behavioral Therapies ◽  
Bdnf Signaling ◽  
Plastic Changes

AbstractCurrent pharmacotherapies for posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are ineffective for many patients, and often do not restore cognitive dysfunction associated with these disorders. Behavioral therapies, such as exposure therapy, can be effective for treatment-resistant patients. The mechanisms underlying exposure therapy are not well-understood. Fear extinction as an intervention after chronic stress can model the beneficial effects of exposure therapy in rats. Extinction requires neuronal activity and protein synthesis in the infralimbic (IL) cortex for its beneficial effects. We hypothesized that extinction requires Brain-Derived Neurotrophic Factor (BDNF) activity in the IL cortex to reverse stress-induced cognitive flexibility impairments. Extinction learning reversed set-shifting deficits induced by Chronic Unpredictable Stress (CUS), tested 24 h after extinction. Blocking BDNF signaling in the IL cortex during extinction by local administration of a neutralizing antibody prevented the beneficial effects of extinction on set shifting after stress. Extinction induced activation of the BDNF TrkB receptor, and signaling pathways associated with BDNF (Akt and Erk). Administration of exogenous BDNF into IL cortex in the absence of extinction was sufficient to reverse the effects of stress on set shifting. The effects of extinction were prevented by blocking either Erk or Akt signaling in the IL cortex, whereas the effects of exogenous BDNF were dependent on Erk, but not Akt, signaling. Our observations suggest that BDNF-Erk signaling induced by extinction underlies plastic changes that can reverse or counteract the effects of chronic stress in the IL cortex.

scholarly journals Role of CXC chemokine receptor type 4 as a lactoferrin receptor

2017 ◽  
Vol 95 (1) ◽  
pp. 57-63 ◽  
Author(s):  
Yoshiharu Takayama ◽  
Reiji Aoki ◽  
Ryo Uchida ◽  
Atsushi Tajima ◽  
Ayako Aoki-Yoshida
Keyword(s):  
Biological Activities ◽  
Ldl Receptor ◽  
Neutralizing Antibody ◽  
Human Keratinocytes ◽  
Akt Signaling ◽  
Target Cells ◽  
Bovine Lactoferrin ◽  
Lactoferrin Receptor ◽  
Stromal Cell Derived Factor ◽  
The Many

Lactoferrin exerts its biological activities by interacting with receptors on target cells, including LDL receptor-related protein-1 (LRP-1/CD91), intelectin-1 (omentin-1), and Toll-like receptor 4 (TLR4). However, the effects mediated by these receptors are not sufficient to fully explain the many functions of lactoferrin. C-X-C-motif cytokine receptor 4 (CXCR4) is a ubiquitously expressed G-protein coupled receptor for stromal cell-derived factor-1 (SDF-1/CXCL12). Lactoferrin was found to be as capable as SDF-1 in blocking infection by an HIV variant that uses CXCR4 as a co-receptor (X4-tropic HIV), suggesting that lactoferrin interacts with CXCR4. We addressed whether CXCR4 acts as a lactoferrin receptor using HaCaT human keratinocytes and Caco-2 human intestinal cells. We found that bovine lactoferrin interacted with CXCR4-containing lipoparticles, and that this interaction was not antagonized by SDF-1. In addition, activation of Akt in response to lactoferrin was abrogated by AMD3100, a small molecule inhibitor of CXCR4, or by a CXCR4-neutralizing antibody, suggesting that CXCR4 functions as a lactoferrin receptor able to mediate activation of the PI3K–Akt signaling pathway. Lactoferrin stimulation mimicked many aspects of SDF-1-induced CXCR4 activity, including receptor dimerization, tyrosine phosphorylation, and ubiquitination. Cycloheximide chase assays indicated that turnover of CXCR4 was accelerated in response to lactoferrin. These results indicate that CXCR4 is a potent lactoferrin receptor that mediates lactoferrin-induced activation of Akt signaling.

scholarly journals Roles of multiple lipid mediators in stress and depression

2019 ◽  
Vol 31 (9) ◽  
pp. 579-587 ◽  
Author(s):  
Tomoyuki Furuyashiki ◽  
Satoshi Akiyama ◽  
Shiho Kitaoka
Keyword(s):  
Chronic Stress ◽  
Social Defeat ◽  
Lipid Mediators ◽  
Mental Illnesses ◽  
Lipid Mediator ◽  
Receptor Subtype ◽  
Social Defeat Stress ◽  
Beneficial Effects ◽  
Prostaglandin Synthase ◽  
Depressive Patients

AbstractProlonged or excessive stress may induce emotional and cognitive disturbances, and is a risk factor for mental illnesses. Using rodent chronic stress models of depression, roles of multiple lipid mediators related to inflammation have been revealed in chronic stress-induced emotional alterations. Prostaglandin (PG) E2, an arachidonic acid (AA)-derived lipid mediator, and its receptor subtype EP1 mediate depression-like behavior induced by repeated social defeat stress through attenuating prefrontal dopaminergic activity. Repeated social defeat stress activates microglia through innate immune receptors, and induces PGE2 synthesis through cyclooxygenase-1, a prostaglandin synthase enriched in microglia. PGD2, another AA-derived lipid mediator, has been implicated in depression induced by chronic stress, although either pro-depressive or anti-depressive actions have been reported. Chronic stress up-regulates hippocampal expression of 5-lipoxygenase, hence synthesis of cysteinyl leukotrienes, thereby inducing depression through their receptors. Consistent with beneficial effects of n-3 fatty acids in the diet of depressive patients, resolvins—a novel class of pro-resolving lipid mediators—in the brain attenuate neuroinflammation-associated depression. These findings in animal models of depression offer lipid mediators and related molecules as novel therapeutic targets for treating depression. To translate these findings into clinics, translational biomarkers to visualize lipid mediator profiles in depressive patients need to be established.

Shared Transcriptional Signatures in Major Depressive Disorder and Mouse Chronic Stress Models

2020 ◽  
Vol 87 (9) ◽  
pp. S222
Author(s):  
Joseph Scarpa ◽  
Mena Fatma ◽  
Yong-Hwee E. Loh ◽  
Said Romaric Traore ◽  
Théo Stefan ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Chronic Stress ◽  
Major Depressive ◽  
Stress Models

scholarly journals Characterization of GABAergic Marker Expression in the Chronic Unpredictable Stress Model of Depression

2017 ◽  
Vol 1 ◽  
pp. 247054701772045 ◽  
Author(s):  
Mounira Banasr ◽  
Ashley Lepack ◽  
Corey Fee ◽  
Vanja Duric ◽  
Jaime Maldonado-Aviles ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Prefrontal Cortex ◽  
Depressive Disorder ◽  
Protein Expression ◽  
Neuropeptide Y ◽  
Chronic Stress ◽  
Gabaergic Interneurons ◽  
Chronic Unpredictable Stress ◽  
Major Depressive

Background Evidence continues to build suggesting that the GABAergic neurotransmitter system is altered in brains of patients with major depressive disorder. However, there is little information available related to the extent of these changes or the potential mechanisms associated with these alterations. As stress is a well-established precipitant to depressive episodes, we sought to explore the impact of chronic stress on GABAergic interneurons. Methods Using western blot analyses and quantitative real-time polymerase chain reaction, we assessed the effects of five-weeks of chronic unpredictable stress exposure on the expression of GABA-synthesizing enzymes (GAD65 and GAD67), calcium-binding proteins (calbindin, parvalbumin, and calretinin), and neuropeptides co-expressed in GABAergic neurons (somatostatin, neuropeptide Y, vasoactive intestinal peptide, and cholecystokinin) in the prefrontal cortex and hippocampus of rats. We also investigated the effects of corticosterone and dexamethasone exposure on these markers in vitro in primary cortical and hippocampal cultures. Results We found that chronic unpredictable stress induced significant reductions of GAD67 protein levels in both the prefrontal cortex and hippocampus of chronic unpredictable stress-exposed rats but did not detect changes in GAD65 protein expression. Similar protein expression changes were found in vitro in cortical neurons. In addition, our results provide clear evidence of reduced markers of interneuron population(s), namely somatostatin and neuropeptide Y, in the prefrontal cortex, suggesting these cell types may be selectively vulnerable to chronic stress. Conclusion Together, this work highlights that chronic stress induces regional and cell type-selective effects on GABAergic interneurons in rats. These findings provide additional supporting evidence that stress-induced GABA neuron dysfunction and cell vulnerability play critical roles in the pathophysiology of stress-related illnesses, including major depressive disorder.

P.1.a.032 Beneficial effects of Sirtuin 2 inhibition in a mouse model of chronic stress

2015 ◽  
Vol 25 ◽  
pp. S175
Author(s):  
M. Erburu ◽  
I. Muñoz-Cobo ◽  
E. Beltrán ◽  
E. Puerta ◽  
R. Tordera
Keyword(s):  
Mouse Model ◽  
Chronic Stress ◽  
Beneficial Effects

scholarly journals Neurobiology of Chronic Stress-Related Psychiatric Disorders: Evidence from Molecular Imaging Studies

2017 ◽  
Vol 1 ◽  
pp. 247054701771091 ◽  
Author(s):  
Margaret T. Davis ◽  
Sophie E. Holmes ◽  
Robert H. Pietrzak ◽  
Irina Esterlis
Keyword(s):  
Molecular Imaging ◽  
Chronic Stress ◽  
Single Photon ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Single Photon Emission ◽  
Major Depressive ◽  
Positron Emission ◽  
Single Photon Emission Computed ◽  
Photon Emission Computed Tomography

Chronic stress accounts for billions of dollars of economic loss annually in the United States alone, and is recognized as a major source of disability and mortality worldwide. Robust evidence suggests that chronic stress plays a significant role in the onset of severe and impairing psychiatric conditions, including major depressive disorder, bipolar disorder, and posttraumatic stress disorder. Application of molecular imaging techniques such as positron emission tomography and single photon emission computed tomography in recent years has begun to provide insight into the molecular mechanisms by which chronic stress confers risk for these disorders. The present paper provides a comprehensive review and synthesis of all positron emission tomography and single photon emission computed tomography imaging publications focused on the examination of molecular targets in individuals with major depressive disorder, posttraumatic stress disorder, or bipolar disorder to date. Critical discussion of discrepant findings and broad strengths and weaknesses of the current body of literature is provided. Recommended future directions for the field of molecular imaging to further elucidate the neurobiological substrates of chronic stress-related disorders are also discussed. This article is part of the inaugural issue for the journal focused on various aspects of chronic stress.

scholarly journals βCommon Receptor Mediates Erythropoietin-Conferred Protection on OxLDL-Induced Lipid Accumulation and Inflammation in Macrophages

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Tzong-Shyuan Lee ◽  
Kuo-Yun Lu ◽  
Yuan-Bin Yu ◽  
Hsueh-Te Lee ◽  
Feng-Chuan Tsai
Keyword(s):  
Lipid Accumulation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Neutralizing Antibody ◽  
Foam Cells ◽  
Beneficial Effects ◽  
Inflammatory Protein ◽  
Common Receptor ◽  
Macrophage Foam Cells ◽  
Key Factor

Erythropoietin (EPO), the key factor for erythropoiesis, also protects macrophage foam cells from lipid accumulation, yet the definitive mechanisms are not fully understood.βcommon receptor (βCR) plays a crucial role in the nonhematopoietic effects of EPO. In the current study, we investigated the role ofβCR in EPO-mediated protection in macrophages against oxidized low-density lipoprotein- (oxLDL-) induced deregulation of lipid metabolism and inflammation. Here, we show thatβCR expression was mainly in foamy macrophages of atherosclerotic aortas from apolipoprotein E-deficient mice. Results of confocal microscopy and immunoprecipitation analyses revealed thatβCR was colocalized and interacted with EPO receptor (EPOR) in macrophages. Inhibition ofβCR activation by neutralizing antibody or small interfering RNA (siRNA) abolished the EPO-conferred protection in oxLDL-induced lipid accumulation. Furthermore, EPO-promoted cholesterol efflux and upregulation of ATP-binding cassette (ABC) transporters ABCA1 and ABCG1 were prevented by pretreatment withβCR neutralizing antibody orβCR siRNA. Additionally, blockage ofβCR abrogated the EPO-conferred anti-inflammatory action on oxLDL-induced production of macrophage inflammatory protein-2. Collectively, our findings suggest thatβCR may play an important role in the beneficial effects of EPO against oxLDL-elicited dysfunction of macrophage foam cells.

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