International Journal of Molecular Sciences

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18 pages, 2509 KiB

Open AccessArticle

Elevated Expression of HSP72 in the Prefrontal Cortex and Hippocampus of Rats Subjected to Chronic Mild Stress and Treated with Imipramine

by Adam Bielawski, Agnieszka Zelek-Molik, Katarzyna Rafa-Zabłocka, Marta Kowalska, Piotr Gruca, Mariusz Papp and Irena Nalepa

Int. J. Mol. Sci. 2024, 25(1), 243; https://doi.org/10.3390/ijms25010243 - 23 Dec 2023

Cited by 1 | Viewed by 835

Abstract

The HSP70 and HSP90 family members belong to molecular chaperones that exhibit protective functions during the cellular response to stressful agents. We investigated whether the exposure of rats to chronic mild stress (CMS), a validated model of depression, affects the expression of HSP70 [...] Read more.

The HSP70 and HSP90 family members belong to molecular chaperones that exhibit protective functions during the cellular response to stressful agents. We investigated whether the exposure of rats to chronic mild stress (CMS), a validated model of depression, affects the expression of HSP70 and HSP90 in the prefrontal cortex (PFC), hippocampus (HIP) and thalamus (Thal). Male Wistar rats were exposed to CMS for 3 or 8 weeks. The antidepressant imipramine (IMI, 10 mg/kg, i.p., daily) was introduced in the last five weeks of the long-term CMS procedure. Depressive-like behavior was verified by the sucrose consumption test. The expression of mRNA and protein was quantified by real-time PCR and Western blot, respectively. In the 8-week CMS model, stress alone elevated HSP72 and HSP90B mRNA expression in the HIP. HSP72 mRNA was increased in the PFC and HIP of rats not responding to IMI treatment vs. IMI responders. The CMS exposure increased HSP72 protein expression in the cytosolic fraction of the PFC and HIP, and this effect was diminished by IMI treatment. Our results suggest that elevated levels of HSP72 may serve as an important indicator of neuronal stress reactions accompanying depression pathology and could be a potential target for antidepressant strategy. Full article

(This article belongs to the Special Issue Stress-Related Disorders and Depression: From Molecular Basis to Therapy)

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16 pages, 2699 KiB

Open AccessArticle

The Impact of Mild Chronic Stress and Maternal Experience in the Fmr1 Mouse Model of Fragile X Syndrome

by Enejda Subashi, Valerie Lemaire, Valeria Petroni and Susanna Pietropaolo

Int. J. Mol. Sci. 2023, 24(14), 11398; https://doi.org/10.3390/ijms241411398 - 13 Jul 2023

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Abstract

Fragile X syndrome (FXS) is a pervasive developmental disorder and the most common monogenic cause of autism spectrum disorder (ASD). Female heterozygous (HET) carriers play a major role in the transmission of the pathology and present several FXS- and ASD-like behavioral alterations. Despite [...] Read more.

Fragile X syndrome (FXS) is a pervasive developmental disorder and the most common monogenic cause of autism spectrum disorder (ASD). Female heterozygous (HET) carriers play a major role in the transmission of the pathology and present several FXS- and ASD-like behavioral alterations. Despite their clear genetic origins, FXS symptoms are known to be modulated by environmental factors, e.g., exposure to chronic stress, especially during critical life periods, such as pregnancy. Pregnancy, together with pups’ care, constitutes maternal experience, i.e., another powerful environmental factor affecting several neurobehavioral functions in females. Here we investigated the impact of maternal experience on the long-term effects of stress in Fmr1-HET female mice. Our findings demonstrated that the behavioral abnormalities of HET females, i.e., hyperactivity and memory deficits, were unaffected by stress or maternal experience. In contrast, stress, independently of maternal experience, induced the appearance of cognitive deficits in WT mice. Maternal experience increased anxiety levels in all mice and enhanced their corticosterone levels, concomitantly promoting the effects of stress on social communication and adrenal glands. In translational terms, these results advance our understanding of the environmental modulation of the behavioral alterations observed in FXS female carriers and highlight the long-term impact of maternal experience and its interactions with chronic stress. Full article

(This article belongs to the Special Issue Stress-Related Disorders and Depression: From Molecular Basis to Therapy)

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24 pages, 2809 KiB

Open AccessArticle

Effects of a True Prophylactic Treatment on Hippocampal and Amygdala Synaptic Plasticity and Gene Expression in a Rodent Chronic Stress Model of Social Defeat

by Eric T. Winzenried, Anna C. Everett, Erin R. Saito, Roxanne M. Miller, Taylor Johnson, Eliza Neal, Zachary Boyce, Calvin Smith, Chloe Jensen, Spencer Kimball, Adam Brantley, Gabriel Melendez, Devin Moffat, Erin Davis, Lyndsey Aponik, Tyler Crofts, Bryson Dabney and Jeffrey G. Edwards

Int. J. Mol. Sci. 2023, 24(13), 11193; https://doi.org/10.3390/ijms241311193 - 7 Jul 2023

Cited by 1 | Viewed by 2681

Abstract

Post-traumatic stress disorder (PTSD) is a complex stress-related disorder induced by exposure to traumatic stress that is characterized by symptoms of re-experiencing, avoidance, and hyper-arousal. While it is widely accepted that brain regions involved in emotional regulation and memory—e.g., the amygdala and hippocampus—are [...] Read more.

Post-traumatic stress disorder (PTSD) is a complex stress-related disorder induced by exposure to traumatic stress that is characterized by symptoms of re-experiencing, avoidance, and hyper-arousal. While it is widely accepted that brain regions involved in emotional regulation and memory—e.g., the amygdala and hippocampus—are dysregulated in PTSD, the pathophysiology of the disorder is not well defined and therefore, pharmacological interventions are extremely limited. Because stress hormones norepinephrine and cortisol (corticosterone in rats) are heavily implicated in the disorder, we explored whether preemptively and systemically antagonizing β-adrenergic and glucocorticoid receptors with propranolol and mifepristone are sufficient to mitigate pathological changes in synaptic plasticity, gene expression, and anxiety induced by a modified social defeat (SD) stress protocol. Young adult, male Sprague Dawley rats were initially pre-screened for anxiety. The rats were then exposed to SD and chronic light stress to induce anxiety-like symptoms. Drug-treated rats were administered propranolol and mifepristone injections prior to and continuing throughout SD stress. Using competitive ELISAs on plasma, field electrophysiology at CA1 of the ventral hippocampus (VH) and the basolateral amygdala (BLA), quantitative RT-PCR, and behavior assays, we demonstrate that our SD stress increased anxiety-like behavior, elevated long-term potentiation (LTP) in the VH and BLA, and altered the expression of mineralocorticoid, glucocorticoid, and glutamate receptors. These measures largely reverted to control levels with the administration of propranolol and mifepristone. Our findings indicate that SD stress increases LTP in the VH and BLA and that prophylactic treatment with propranolol and mifepristone may have the potential in mitigating these and other stress-induced effects. Full article

(This article belongs to the Special Issue Stress-Related Disorders and Depression: From Molecular Basis to Therapy)

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12 pages, 2797 KiB

Open AccessArticle

Sedative-Hypnotic Effects of Glycine max Merr. Extract and Its Active Ingredient Genistein on Electric-Shock-Induced Sleep Disturbances in Rats

by Minsook Ye, SunYoung Lee, Hyo Jeong Yu, Kyu-Ri Kim, Hyun-Jung Park, In-Cheol Kang, Soon Ah Kang, Young-Shin Chung and Insop Shim

Int. J. Mol. Sci. 2023, 24(8), 7043; https://doi.org/10.3390/ijms24087043 - 11 Apr 2023

Cited by 1 | Viewed by 1772

Abstract

Glycine max Merr. (GM) is a functional food that provides many beneficial phytochemicals. However, scientific evidence of its antidepressive and sedative activities is scarce. The present study was designed to investigate the antidepressive and calmative effects of GM and its biologically active [...] Read more.

Glycine max Merr. (GM) is a functional food that provides many beneficial phytochemicals. However, scientific evidence of its antidepressive and sedative activities is scarce. The present study was designed to investigate the antidepressive and calmative effects of GM and its biologically active compound, genistein (GE), using electroencephalography (EEG) analysis in an electric foot shock (EFS)-stressed rat. The underlying neural mechanisms of their beneficial effects were determined by assessing corticotropin-releasing factor (CRF), serotonin (5-HT), and c-Fos immunoreactivity in the brain using immunohistochemical methods. In addition, the 5-HT2C receptor binding assay was performed because it is considered a major target of antidepressants and sleep aids. In the binding assay, GM displayed binding affinity to the 5-HT2C receptor (IC50 value of 14.25 ± 11.02 µg/mL). GE exhibited concentration-dependent binding affinity, resulting in the binding of GE to the 5-HT_2C receptor (IC50, 77.28 ± 26.57 mg/mL). Administration of GM (400 mg/kg) increased non-rapid eye movement (NREM) sleep time. Administration of GE (30 mg/kg) decreased wake time and increased rapid eye movement (REM) and NREM sleep in EPS-stressed rats. In addition, treatment with GM and GE significantly decreased c-Fos and CRF expression in the paraventricular nucleus (PVN) and increased 5-HT levels in the dorsal raphe in the brain. Overall, these results suggest that GM and GE have antidepressant-like effects and are effective in sleep maintenance. These results will benefit researchers in developing alternatives to decrease depression and prevent sleep disorders. Full article

(This article belongs to the Special Issue Stress-Related Disorders and Depression: From Molecular Basis to Therapy)

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19 pages, 6470 KiB

Open AccessArticle

A Novel Early Life Stress Model Affects Brain Development and Behavior in Mice

by Hyun Seung Shin, Soo Min Choi, Seung Hyun Lee, Ha Jung Moon and Eui-Man Jung

Int. J. Mol. Sci. 2023, 24(5), 4688; https://doi.org/10.3390/ijms24054688 - 28 Feb 2023

Cited by 4 | Viewed by 3440

Abstract

Early life stress (ELS) in developing children has been linked to physical and psychological sequelae in adulthood. In the present study, we investigated the effects of ELS on brain and behavioral development by establishing a novel ELS model that combined the maternal separation [...] Read more.

Early life stress (ELS) in developing children has been linked to physical and psychological sequelae in adulthood. In the present study, we investigated the effects of ELS on brain and behavioral development by establishing a novel ELS model that combined the maternal separation paradigm and mesh platform condition. We found that the novel ELS model caused anxiety- and depression-like behaviors and induced social deficits and memory impairment in the offspring of mice. In particular, the novel ELS model induced more enhanced depression-like behavior and memory impairment than the maternal separation model, which is the established ELS model. Furthermore, the novel ELS caused upregulation of arginine vasopressin expression and downregulation of GABAergic interneuron markers, such as parvalbumin (PV), vasoactive intestinal peptide, and calbindin-D_28k (CaBP-28k), in the brains of the mice. Finally, the offspring in the novel ELS model showed a decreased number of cortical PV-, CaBP-28k-positive cells and an increased number of cortical ionized calcium-binding adaptors-positive cells in their brains compared to mice in the established ELS model. Collectively, these results indicated that the novel ELS model induced more negative effects on brain and behavioral development than the established ELS model. Full article

(This article belongs to the Special Issue Stress-Related Disorders and Depression: From Molecular Basis to Therapy)

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21 pages, 2963 KiB

Open AccessArticle

Cognitive and Emotional Symptoms Induced by Chronic Stress Are Regulated by EGR1 in a Subpopulation of Hippocampal Pyramidal Neurons

by Anna Sancho-Balsells, Sara Borràs-Pernas, Verónica Brito, Jordi Alberch, Jean-Antoine Girault and Albert Giralt

Int. J. Mol. Sci. 2023, 24(4), 3833; https://doi.org/10.3390/ijms24043833 - 14 Feb 2023

Cited by 5 | Viewed by 2428

Abstract

Chronic stress is a core risk factor for developing a myriad of neurological disorders, including major depression. The chronicity of such stress can lead to adaptive responses or, on the contrary, to psychological maladaptation. The hippocampus is one of the most affected brain [...] Read more.

Chronic stress is a core risk factor for developing a myriad of neurological disorders, including major depression. The chronicity of such stress can lead to adaptive responses or, on the contrary, to psychological maladaptation. The hippocampus is one of the most affected brain regions displaying functional changes in chronic stress. Egr1, a transcription factor involved in synaptic plasticity, is a key molecule regulating hippocampal function, but its role in stress-induced sequels has been poorly addressed. Emotional and cognitive symptoms were induced in mice by using the chronic unpredictable mild stress (CUMS) protocol. We used inducible double-mutant Egr1-CreERT2 x R26RCE mice to map the formation of Egr1-dependent activated cells. Results show that short- (2 days) or long-term (28 days) stress protocols in mice induce activation or deactivation, respectively, of hippocampal CA1 neural ensembles in an Egr1-activity-dependent fashion, together with an associated dendritic spine pathology. In-depth characterization of these neural ensembles revealed a deep-to-superficial switch in terms of Egr1-dependent activation of CA1 pyramidal neurons. To specifically manipulate deep and superficial pyramidal neurons of the hippocampus, we then used Chrna7-Cre (to express Cre in deep neurons) and Calb1-Cre mice (to express Cre in superficial neurons). We found that specific manipulation of superficial but not deep pyramidal neurons of the CA1 resulted in the amelioration of depressive-like behaviors and the restoration of cognitive impairments induced by chronic stress. In summary, Egr1 might be a core molecule driving the activation/deactivation of hippocampal neuronal subpopulations underlying stress-induced alterations involving emotional and cognitive sequels. Full article

(This article belongs to the Special Issue Stress-Related Disorders and Depression: From Molecular Basis to Therapy)

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17 pages, 1390 KiB

Open AccessArticle

Psychedelic-Induced Serotonin 2A Receptor Downregulation Does Not Predict Swim Stress Coping in Mice

by Błażej D. Pędzich, Mireia Medrano, An Buckinx, Ilse Smolders and Dimitri De Bundel

Int. J. Mol. Sci. 2022, 23(23), 15284; https://doi.org/10.3390/ijms232315284 - 4 Dec 2022

Cited by 3 | Viewed by 5157

Abstract

Serotoninergic psychedelics such as psilocybin have been reported to elicit a long-lasting reduction in depressive symptoms. Although the main target for serotoninergic psychedelics, serotonin type 2A receptor (5-HT_2A), has been established, the possible mechanism of the antidepressant action of psychedelics remains [...] Read more.

Serotoninergic psychedelics such as psilocybin have been reported to elicit a long-lasting reduction in depressive symptoms. Although the main target for serotoninergic psychedelics, serotonin type 2A receptor (5-HT_2A), has been established, the possible mechanism of the antidepressant action of psychedelics remains unknown. Using the mouse forced swim test model, we examined whether the administration of the synthetic serotoninergic psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI) would modulate 5-HT_2A receptor levels in the medial prefrontal cortex (mPFC) and revert stress-induced changes in behavior. Mice subjected to swim stress developed a passive stress-coping strategy when tested in the forced swim test 6 days later. This change in behavior was not associated with the hypothesized increase in 5-HT_2A receptor-dependent head twitch behaviors or consistent changes in 5-HT_2A receptor levels in the mPFC. When DOI was administered 1 day before the forced swim test, a low dose (0.2 mg/kg i.p.) unexpectedly increased immobility while a high dose (2 mg/kg i.p.) had no significant effect on immobility. Nevertheless, DOI evoked a dose-dependent decrease in 5-HT_2A levels in the mPFC of mice previously exposed to swim stress. Our findings do not support the hypothesis that the downregulation of 5-HT_2A receptors in the mPFC contributes to the antidepressant-like properties of serotoninergic psychedelics. Full article

(This article belongs to the Special Issue Stress-Related Disorders and Depression: From Molecular Basis to Therapy)

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15 pages, 1806 KiB

Open AccessArticle

Involvement of the IL-6 Signaling Pathway in the Anti-Anhedonic Effect of the Antidepressant Agomelatine in the Chronic Mild Stress Model of Depression

by Andrea C. Rossetti, Maria Serena Paladini, Cesar Augusto Brüning, Vittoria Spero, Maria Grazia Cattaneo, Giorgio Racagni, Mariusz Papp, Marco A. Riva and Raffaella Molteni

Int. J. Mol. Sci. 2022, 23(20), 12453; https://doi.org/10.3390/ijms232012453 - 18 Oct 2022

Cited by 4 | Viewed by 2424

Abstract

Neuroinflammation has emerged as an important factor in the molecular underpinnings of major depressive disorder (MDD) pathophysiology and in the mechanism of action of antidepressants. Among the inflammatory mediators dysregulated in depressed patients, interleukin (IL)-6 has recently been proposed to play a crucial [...] Read more.

Neuroinflammation has emerged as an important factor in the molecular underpinnings of major depressive disorder (MDD) pathophysiology and in the mechanism of action of antidepressants. Among the inflammatory mediators dysregulated in depressed patients, interleukin (IL)-6 has recently been proposed to play a crucial role. IL-6 activates a signaling pathway comprising the JAK/STAT proteins and characterized by a specific negative feedback loop exerted by the cytoplasmic protein suppressor of cytokine signalling-3 (SOCS3). On these bases, here, we explored the potential involvement of IL-6 signaling in the ability of the antidepressant drug agomelatine to normalize the anhedonic-like phenotype induced in the rat by chronic stress exposure. To this aim, adult male Wistar rats were subjected to the chronic mild stress (CMS) paradigm and chronically treated with vehicle or agomelatine. The behavioral evaluation was assessed by the sucrose consumption test, whereas molecular analyses were performed in the prefrontal cortex. We found that CMS was able to stimulate IL-6 production and signaling, including SOCS3 gene and protein expression, but the SOCS3-mediated feedback-loop inhibition failed to suppress the IL-6 cascade in stressed animals. Conversely, agomelatine treatment normalized the stress-induced decrease in sucrose consumption and restored the negative modulation of the IL-6 signaling via SOCS3 expression and activity. Our results provide additional information about the pleiotropic mechanisms that contribute to agomelatine’s therapeutic effects. Full article

(This article belongs to the Special Issue Stress-Related Disorders and Depression: From Molecular Basis to Therapy)

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16 pages, 1839 KiB

Open AccessArticle

Anxiety-like Behavior and GABAAR/BDZ Binding Site Response to Progesterone Withdrawal in a Stress-Vulnerable Strain, the Wistar Kyoto Rats

by Dannia Islas-Preciado, Gabriela Ugalde-Fuentes, Isabel Sollozo-Dupont, María Eva González Trujano, Nancy Cervantes-Anaya, Erika Estrada-Camarena and Carolina López-Rubalcava

Int. J. Mol. Sci. 2022, 23(13), 7259; https://doi.org/10.3390/ijms23137259 - 30 Jun 2022

Cited by 5 | Viewed by 2250

Abstract

Stress susceptibility could play a role in developing premenstrual anxiety due to abnormalities in the hypothalamus–pituitary–adrenal (HPA) axis and impairments in the GABAA receptors’ benzodiazepine (BDZ) site. Hence, we studied the stress-vulnerable Wistar Kyoto rat strain (WKY) to evaluate progesterone withdrawal (PW) effects [...] Read more.

Stress susceptibility could play a role in developing premenstrual anxiety due to abnormalities in the hypothalamus–pituitary–adrenal (HPA) axis and impairments in the GABAA receptors’ benzodiazepine (BDZ) site. Hence, we studied the stress-vulnerable Wistar Kyoto rat strain (WKY) to evaluate progesterone withdrawal (PW) effects on anxiety, HPA axis response, and to explore indicators of GABAA functionality in the BDZ site. For five days, ovariectomized WKY rats were administered 2.0 mg/kg of progesterone. Twenty-four hours after the last administration, rats were tested in the anxiety-like burying behavior test (BBT) or elevated plus maze test (EPM), and corticosterone was determined. [3H]Flunitrazepam binding autoradiography served as the BDZ binding site index of the GABAA receptor in amygdala nuclei and hippocampus’s dentate gyrus (DG). Finally, different doses of diazepam in PW-WKY rats were tested in the BBT. PW induced anxiety-like behaviors in both BBT and EPM compared with No-PW rats. PW increased corticosterone, but was blunted when combined with PW and BBT. PW increased [3H]Flunitrazepam binding in the DG and central amygdala compared with No-PW rats. Diazepam at a low dose induced an anxiogenic-like response in PW rats, suggesting a paradoxical response to benzodiazepines. Overall, PW induced anxiety-like behavior, a blunted HPA axis response, and higher GABAAR/BZD binding site sensitivity in a stress-vulnerable rat strain. These findings demonstrate the role of stress-susceptibility in GABAAR functionality in a preclinical approximation of PMDD. Full article

(This article belongs to the Special Issue Stress-Related Disorders and Depression: From Molecular Basis to Therapy)

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14 pages, 2021 KiB

Open AccessArticle

Peripheral Serotonin Deficiency Affects Anxiety-like Behavior and the Molecular Response to an Acute Challenge in Rats

by Giulia Sbrini, Sabrina I. Hanswijk, Paola Brivio, Anthonieke Middelman, Michael Bader, Fabio Fumagalli, Natalia Alenina, Judith R. Homberg and Francesca Calabrese

Int. J. Mol. Sci. 2022, 23(9), 4941; https://doi.org/10.3390/ijms23094941 - 29 Apr 2022

Cited by 7 | Viewed by 2678

Abstract

Serotonin is synthetized through the action of tryptophan hydroxylase (TPH) enzymes. While the TPH2 isoform is responsible for the production of serotonin in the brain, TPH1 is expressed in peripheral organs. Interestingly, despite its peripheral localization, alterations of the gene coding for TPH1 [...] Read more.

Serotonin is synthetized through the action of tryptophan hydroxylase (TPH) enzymes. While the TPH2 isoform is responsible for the production of serotonin in the brain, TPH1 is expressed in peripheral organs. Interestingly, despite its peripheral localization, alterations of the gene coding for TPH1 have been related to stress sensitivity and an increased susceptibility for psychiatric pathologies. On these bases, we took advantage of newly generated TPH1^−/− rats, and we evaluated the impact of the lack of peripheral serotonin on the behavior and expression of brain plasticity-related genes under basal conditions and in response to stress. At a behavioral level, TPH1^−/− rats displayed reduced anxiety-like behavior. Moreover, we found that neuronal activation, quantified by the expression of Bdnf and the immediate early gene Arc and transcription of glucocorticoid responsive genes after 1 h of acute restraint stress, was blunted in TPH1^−/− rats in comparison to TPH1^+/+ animals. Overall, we provided evidence for the influence of peripheral serotonin levels in modulating brain functions under basal and dynamic situations. Full article

(This article belongs to the Special Issue Stress-Related Disorders and Depression: From Molecular Basis to Therapy)

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Review

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15 pages, 1052 KiB

Open AccessReview

Psychological Stress-Induced Pathogenesis of Alopecia Areata: Autoimmune and Apoptotic Pathways

by Dongkyun Ahn, Hyungjun Kim, Bombi Lee and Dae-Hyun Hahm

Int. J. Mol. Sci. 2023, 24(14), 11711; https://doi.org/10.3390/ijms241411711 - 20 Jul 2023

Cited by 5 | Viewed by 2547

Abstract

Alopecia areata (AA) is an autoimmune dermatological disease with multifactorial etiology and is characterized by reversible hair loss in patches. AA may be closely related to emotional stress and influenced by psychological factors as part of its pathophysiology; however, its etiology remains predominantly [...] Read more.

Alopecia areata (AA) is an autoimmune dermatological disease with multifactorial etiology and is characterized by reversible hair loss in patches. AA may be closely related to emotional stress and influenced by psychological factors as part of its pathophysiology; however, its etiology remains predominantly unknown. This review aimed to elucidate the association between AA occurrence and the neuropeptide substance P (SP) and corticotropin-releasing hormone (CRH), which are secreted during emotional stress, and have been understood to initiate and advance the etiopathogenesis of AA. Therefore, this review aimed to explain how SP and CRH initiate and contribute to the etiopathogenesis of AA. To assess the etiopathogenesis of AA, we conducted a literature search on PubMed and ClinicalTrials.gov. Overall, several authors described interactions between the hair follicles (HFs) and the stress-associated signaling substances, including SP and CRH, in the etiology of AA; this was attributed to the understanding in that AA can occur without the loss of HFs, similar to that observed in hereditary hair loss with age. Most studies demonstrated that the collapse of “immune privilege” plays a crucial role in the development and exacerbation of the AA; nonetheless, a few studies indicated that substances unrelated to autoimmunity may also cause apoptosis in keratocytes, leading to the development of AA. We investigated both the autoimmune and apoptotic pathways within the etiology of AA and assessed the potential interactions between the key substances of both pathways to evaluate potential therapeutic targets for the treatment of AA. Clinical trials of marketed/unreviewed intervention drugs for AA were also reviewed to determine their corresponding target pathways. Full article

(This article belongs to the Special Issue Stress-Related Disorders and Depression: From Molecular Basis to Therapy)

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14 pages, 2019 KiB

Open AccessReview

Transcriptome Alterations Caused by Social Defeat Stress of Various Durations in Mice and Its Relevance to Depression and Posttraumatic Stress Disorder in Humans: A Meta-Analysis

by Vasiliy V. Reshetnikov, Polina E. Kisaretova and Natalia P. Bondar

Int. J. Mol. Sci. 2022, 23(22), 13792; https://doi.org/10.3390/ijms232213792 - 9 Nov 2022

Cited by 6 | Viewed by 2528

Abstract

The research on molecular causes of stress-associated psychopathologies is becoming highly important because the number of people with depression, generalized anxiety disorder and posttraumatic stress disorders (PTSDs) is steadily increasing every year. Investigation of molecular mechanisms in animal models opens up broad prospects [...] Read more.

The research on molecular causes of stress-associated psychopathologies is becoming highly important because the number of people with depression, generalized anxiety disorder and posttraumatic stress disorders (PTSDs) is steadily increasing every year. Investigation of molecular mechanisms in animal models opens up broad prospects for researchers, but relevant molecular signatures can differ significantly between patients and animal models. In our work, we for the first time carried out a meta-analysis of transcriptome changes in the prefrontal cortex of C57BL/6 mice after 10 and 30 days of social defeat stress (SDS). We then examined possible correlations of these alterations with transcriptome changes found in post-mortem samples from patients with depression or PTSD. Although transcriptional signatures of human psychiatric disorders and SDS did not overlap substantially, our results allowed us to identify the most reproducible changes seen after SDS of various durations. In addition, we were able to identify the genes involved in susceptibility to SDS after 10 days of stress. Taken together, these data help us to elucidate the molecular changes induced by SDS depending on its duration as well as their relevance to the alterations found in depression or PTSD in humans. Full article

(This article belongs to the Special Issue Stress-Related Disorders and Depression: From Molecular Basis to Therapy)

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20 pages, 1029 KiB

Open AccessReview

Running from Stress: Neurobiological Mechanisms of Exercise-Induced Stress Resilience

by Marta Nowacka-Chmielewska, Konstancja Grabowska, Mateusz Grabowski, Patrick Meybohm, Malgorzata Burek and Andrzej Małecki

Int. J. Mol. Sci. 2022, 23(21), 13348; https://doi.org/10.3390/ijms232113348 - 1 Nov 2022

Cited by 10 | Viewed by 6582

Abstract

Chronic stress, even stress of a moderate intensity related to daily life, is widely acknowledged to be a predisposing or precipitating factor in neuropsychiatric diseases. There is a clear relationship between disturbances induced by stressful stimuli, especially long-lasting stimuli, and cognitive deficits in [...] Read more.

Chronic stress, even stress of a moderate intensity related to daily life, is widely acknowledged to be a predisposing or precipitating factor in neuropsychiatric diseases. There is a clear relationship between disturbances induced by stressful stimuli, especially long-lasting stimuli, and cognitive deficits in rodent models of affective disorders. Regular physical activity has a positive effect on the central nervous system (CNS) functions, contributes to an improvement in mood and of cognitive abilities (including memory and learning), and is correlated with an increase in the expression of the neurotrophic factors and markers of synaptic plasticity as well as a reduction in the inflammatory factors. Studies published so far show that the energy challenge caused by physical exercise can affect the CNS by improving cellular bioenergetics, stimulating the processes responsible for the removal of damaged organelles and molecules, and attenuating inflammation processes. Regular physical activity brings another important benefit: increased stress robustness. The evidence from animal studies is that a sedentary lifestyle is associated with stress vulnerability, whereas a physically active lifestyle is associated with stress resilience. Here, we have performed a comprehensive PubMed Search Strategy for accomplishing an exhaustive literature review. In this review, we discuss the findings from experimental studies on the molecular and neurobiological mechanisms underlying the impact of exercise on brain resilience. A thorough understanding of the mechanisms underlying the neuroprotective potential of preconditioning exercise and of the role of exercise in stress resilience, among other things, may open further options for prevention and therapy in the treatment of CNS diseases. Full article

(This article belongs to the Special Issue Stress-Related Disorders and Depression: From Molecular Basis to Therapy)

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23 pages, 1793 KiB

Open AccessReview

Propranolol versus Other Selected Drugs in the Treatment of Various Types of Anxiety or Stress, with Particular Reference to Stage Fright and Post-Traumatic Stress Disorder

by Łukasz Szeleszczuk and Dawid Frączkowski

Int. J. Mol. Sci. 2022, 23(17), 10099; https://doi.org/10.3390/ijms231710099 - 3 Sep 2022

Cited by 9 | Viewed by 14930

Abstract

Propranolol, a non-cardioselective β_1,2 blocker, is most commonly recognised for its application in the therapy of various cardiovascular conditions, such as hypertension, coronary artery disease, and tachyarrhythmias. However, due to its ability to cross the blood–brain barrier and affinity towards multiple macromolecules, [...] Read more.

Propranolol, a non-cardioselective β_1,2 blocker, is most commonly recognised for its application in the therapy of various cardiovascular conditions, such as hypertension, coronary artery disease, and tachyarrhythmias. However, due to its ability to cross the blood–brain barrier and affinity towards multiple macromolecules, not only adrenoreceptors, it has also found application in other fields. For example, it is one of the very few medications successfully applied in the treatment of stage fright. This review focuses on the application of propranolol in the treatment of various types of anxiety and stress, with particular reference to stage fright and post-traumatic stress disorder (PTSD). Both mechanisms of action as well as comparison with other therapies are presented. As those indications for propranolol are, in most countries, considered off-label, this review aims to gather information that can be useful while making a decision about the choice of propranolol as a drug in the treatment of those mental conditions. Full article

(This article belongs to the Special Issue Stress-Related Disorders and Depression: From Molecular Basis to Therapy)

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14 pages, 884 KiB

Open AccessReview

Molecular Basis Underlying the Therapeutic Potential of Vitamin D for the Treatment of Depression and Anxiety

by Bruna R. Kouba, Anderson Camargo, Joana Gil-Mohapel and Ana Lúcia S. Rodrigues

Int. J. Mol. Sci. 2022, 23(13), 7077; https://doi.org/10.3390/ijms23137077 - 25 Jun 2022

Cited by 23 | Viewed by 7194

Abstract

Major depressive disorder and anxiety disorders are common and disabling conditions that affect millions of people worldwide. Despite being different disorders, symptoms of depression and anxiety frequently overlap in individuals, making them difficult to diagnose and treat adequately. Therefore, compounds capable of exerting [...] Read more.

Major depressive disorder and anxiety disorders are common and disabling conditions that affect millions of people worldwide. Despite being different disorders, symptoms of depression and anxiety frequently overlap in individuals, making them difficult to diagnose and treat adequately. Therefore, compounds capable of exerting beneficial effects against both disorders are of special interest. Noteworthily, vitamin D deficiency has been associated with an increased risk of developing depression and anxiety, and individuals with these psychiatric conditions have low serum levels of this vitamin. Indeed, in the last few years, vitamin D has gained attention for its many functions that go beyond its effects on calcium–phosphorus metabolism. Particularly, antioxidant, anti-inflammatory, pro-neurogenic, and neuromodulatory properties seem to contribute to its antidepressant and anxiolytic effects. Therefore, in this review, we highlight the main mechanisms that may underlie the potential antidepressant and anxiolytic effects of vitamin D. In addition, we discuss preclinical and clinical studies that support the therapeutic potential of this vitamin for the management of these disorders. Full article

(This article belongs to the Special Issue Stress-Related Disorders and Depression: From Molecular Basis to Therapy)

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Stress-Related Disorders and Depression: From Molecular Basis to Therapy

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