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1.
J Integr Neurosci ; 23(4): 82, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38682225

RESUMEN

BACKGROUND: Comorbid chronic neuropathic pain (NPP) and anxio-depressive disorders (ADD) have become a serious global public-health problem. The SLIT and NTRK-like 1 (SLITRK1) protein is important for synaptic remodeling and is highly expressed in the amygdala, an important brain region involved in various emotional behaviors. We examined whether SLITRK1 protein in the amygdala participates in NPP and comorbid ADD. METHODS: A chronic NPP mouse model was constructed by L5 spinal nerve ligation; changes in chronic pain and ADD-like behaviors were measured in behavioral tests. Changes in SLITRK1 protein and excitatory synaptic functional proteins in the amygdala were measured by immunofluorescence and Western blot. Adeno-associated virus was transfected into excitatory synaptic neurons in the amygdala to up-regulate the expression of SLITRK1. RESULTS: Chronic NPP-related ADD-like behavior was successfully produced in mice by L5 ligation. We found that chronic NPP and related ADD decreased amygdalar expression of SLITRK1 and proteins important for excitatory synaptic function, including Homer1, postsynaptic density protein 95 (PSD95), and synaptophysin. Virally-mediated SLITRK1 overexpression in the amygdala produced a significant easing of chronic NPP and ADD, and restored the expression levels of Homer1, PSD95, and synaptophysin. CONCLUSION: Our findings indicated that SLITRK1 in the amygdala plays an important role in chronic pain and related ADD, and may prove to be a potential therapeutic target for chronic NPP-ADD comorbidity.


Asunto(s)
Amígdala del Cerebelo , Conducta Animal , Dolor Crónico , Homólogo 4 de la Proteína Discs Large , Proteínas del Tejido Nervioso , Neuralgia , Animales , Masculino , Ratones , Amígdala del Cerebelo/metabolismo , Ansiedad/metabolismo , Ansiedad/fisiopatología , Trastornos de Ansiedad/metabolismo , Trastornos de Ansiedad/fisiopatología , Conducta Animal/fisiología , Dolor Crónico/metabolismo , Dolor Crónico/fisiopatología , Depresión/metabolismo , Depresión/etiología , Depresión/fisiopatología , Trastorno Depresivo/metabolismo , Trastorno Depresivo/fisiopatología , Modelos Animales de Enfermedad , Homólogo 4 de la Proteína Discs Large/metabolismo , Proteínas de Andamiaje Homer/metabolismo , Proteínas de la Membrana/metabolismo , Ratones Endogámicos C57BL , Proteínas del Tejido Nervioso/metabolismo , Neuralgia/metabolismo , Sinaptofisina/metabolismo
2.
J Psychiatr Res ; 174: 101-113, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38626560

RESUMEN

Depressive disorders are widely debilitating psychiatric disease. Despite the considerable progress in the field of depression therapy, extensive research spanning many decades has failed to uncover pathogenic pathways that might aid in the creation of long-acting and rapid-acting antidepressants. Consequently, it is imperative to reconsider existing approaches and explore other targets to improve this area of study. In contemporary times, several scholarly investigations have unveiled that persons who have received a diagnosis of depression, as well as animal models employed to study depression, demonstrate a decrease in both the quantity as well as density of astrocytes, accompanied by alterations in gene expression and morphological attributes. Astrocytes rely on a diverse array of channels and receptors to facilitate their neurotransmitter transmission inside tripartite synapses. This study aimed to investigate the potential processes behind the development of depression, specifically focusing on astrocyte-associated neuroinflammation and the involvement of several molecular components such as connexin 43, potassium channel Kir4.1, aquaporin 4, glutamatergic aspartic acid transporter protein, SLC1A2 or GLT-1, glucocorticoid receptors, 5-hydroxytryptamine receptor 2B, and autophagy, that localized on the surface of astrocytes. The study also explores novel approaches in the treatment of depression, with a focus on astrocytes, offering innovative perspectives on potential antidepressant medications.


Asunto(s)
Astrocitos , Astrocitos/metabolismo , Astrocitos/efectos de los fármacos , Humanos , Animales , Antidepresivos/farmacología , Trastorno Depresivo/tratamiento farmacológico , Trastorno Depresivo/metabolismo , Trastorno Depresivo/terapia , Enfermedades Neuroinflamatorias/tratamiento farmacológico
5.
Acta Neuropsychiatr ; 36(3): 129-138, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38178717

RESUMEN

Bradykinin (BK), a well-studied mediator of physiological and pathological processes in the peripheral system, has garnered less attention regarding its function in the central nervous system, particularly in behavioural regulation. This review delves into the historical progression of research focused on the behavioural effects of BK and other drugs that act via similar mechanisms to provide new insights into the pathophysiology and pharmacotherapy of psychiatric disorders. Evidence from experiments with animal models indicates that BK modulates defensive reactions associated with panic symptoms and the response to acute stressors. The mechanisms are not entirely understood but point to complex interactions with other neurotransmitter systems, such as opioids, and intracellular signalling cascades. By addressing the existing research gaps in this field, we present new proposals for future research endeavours to foster a new era of investigation regarding BK's role in emotional regulation. Implications for psychiatry, chiefly for panic and depressive disorders are also discussed.


Asunto(s)
Bradiquinina , Sistema Nervioso Central , Humanos , Animales , Bradiquinina/metabolismo , Sistema Nervioso Central/metabolismo , Sistema Nervioso Central/efectos de los fármacos , Trastorno de Pánico/metabolismo , Trastornos Mentales/metabolismo , Trastornos Mentales/tratamiento farmacológico , Trastorno Depresivo/metabolismo , Trastorno Depresivo/tratamiento farmacológico
6.
Pharmacol Rep ; 76(1): 51-71, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38194217

RESUMEN

BACKGROUND: Maternal elevated glucocorticoid levels during pregnancy can affect the developing fetus, permanently altering the structure and function of its brain throughout life. Excessive action of these hormones is known to contribute to psychiatric disorders, including depression. MATERIALS: The study was performed in a rat model of depression based on prenatal administration of dexamethasone (DEX) in late pregnancy (0.1 mg/kg, days 14-21). We evaluated the effects of prenatal DEX treatment on the cognition and bioenergetic signaling pathways in the brain of adult male rats, in the frontal cortex and hippocampus, and in response to stress in adulthood, using behavioral and biochemical test batteries. RESULTS: We revealed cognitive deficits in rats prenatally treated with DEX. At the molecular level, a decrease in the orexin A and orexin B levels and downregulation of the AMPK-SIRT1-PGC1α transduction pathway in the frontal cortex of these animals were observed. In the hippocampus, a decreased expression of orexin B was found and changes in the MR/GR ratio were demonstrated. Furthermore, an increase in HDAC5 level triggered by the prenatal DEX treatment in both brain structures and a decrease in MeCP2 level in the hippocampus were reported. CONCLUSIONS: Our study demonstrated that prenatal DEX treatment is associated with cognitive dysfunction and alterations in various proteins leading to metabolic changes in the frontal cortex, while in the hippocampus adaptation mechanisms were activated. The presented results imply that different pathophysiological metabolic processes may be involved in depression development, which may be useful in the search for novel therapies.


Asunto(s)
Trastorno Depresivo , Efectos Tardíos de la Exposición Prenatal , Humanos , Femenino , Ratas , Masculino , Animales , Embarazo , Orexinas/metabolismo , Dexametasona/farmacología , Depresión/metabolismo , Encéfalo/metabolismo , Glucocorticoides/metabolismo , Hipocampo , Modelos Animales , Trastorno Depresivo/tratamiento farmacológico , Trastorno Depresivo/metabolismo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Receptores de Glucocorticoides/metabolismo
7.
Brain Res ; 1822: 148664, 2024 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-37923002

RESUMEN

Depressive disorders is a serious mental illness, and its underlying pathological mechanisms remain unclear. The overactivation of microglia and neuroinflammation are thought to play an essential role in the occurrence and development of depressive disorders. TREM2, an immune protein mainly expressed in microglia, is an important part of nerve cells involved in inflammatory response. Corticosterone (CORT) is often referred to as a stress hormone and plays a role in the immune system and stress response. Therefore, this study investigated the role of TREM2 in CORT-induced BV2 cell damage and preliminarily analyzed the effects of TREM2 on JAK2/STAT3 signaling pathway and microglia polarization. The cell model of CORT-induced depression in vitro was established, and the effect of CORT on the activity of BV2 microglia was detected by CCK8. Plasmid transfection was used to overexpress and interfere with TREM2 in BV2 cells cultured by CORT. Western blotting, PCR, and ELISA analyzed the expression of related proteins and inflammatory factors. The results showed that CORT could affect BV2 cell proliferation and TREM2 levels. In the presence of CORT, overexpression of TREM2 decreased the levels of TNF-α, IL-1ß, and IL-6 and increased the levels of IL-10. Interference with TREM2 increased the levels of TNF-α, IL-1ß, and IL-6 and decreased the levels of IL-10. TREM2 can affect the release of inflammatory factors through the JAK2/STAT3 signaling pathway and regulate the M1/M2 phenotypic transformation of microglia. TREM2 plays a role in regulating CORT-induced inflammatory responses, revealing the influence of TREM2 on the neuroinflammatory pathogenesis of depressive disorders and suggesting that TREM2 may be a new target for the prevention and treatment of depressive disorders.


Asunto(s)
Corticosterona , Trastorno Depresivo , Enfermedades Neuroinflamatorias , Humanos , Corticosterona/metabolismo , Corticosterona/farmacología , Trastorno Depresivo/metabolismo , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Lipopolisacáridos/farmacología , Glicoproteínas de Membrana/metabolismo , Microglía/metabolismo , Receptores Inmunológicos/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
8.
Int Immunopharmacol ; 123: 110677, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37523973

RESUMEN

Eucommia ulmoides Oliv (EUO) is a traditional therapeutic drug that tonifies the liver and kidney and may improve depression. However, the mechanism of action of the main component, aucubin (AU), is unknown. To study the therapeutic effect of AU, we constructed a chronic unpredictable mild stress (CUMS) depression model in mice. Depression-like behaviors, pathological damage, hormonal changes, inflammation, intranuclear expression of glucocorticoidreceptor (GR), and hippocampal protein expression were assessed. Immunofluorescence staining of the hippocampus showed that CUMS decreased neuronal regeneration, and axons were observed to be reduced and broken. Intracellular GR expression decreased in the hippocampus and hypothalamus, and serum levels of stress hormones increased. Furthermore, molecular changes indicative of pyroptosis were observed. AU administration reversed these changes and significantly improved the depression-like behavior induced by CUMS. Our results suggested that AU improves depression by promoting the intranuclear expression of GR and inhibiting nuclear factor-kappa B-mediated inflammatory activation-driven cell pyroptosis.


Asunto(s)
Trastorno Depresivo , FN-kappa B , Animales , Ratones , Depresión/tratamiento farmacológico , Depresión/metabolismo , Trastorno Depresivo/tratamiento farmacológico , Trastorno Depresivo/metabolismo , Modelos Animales de Enfermedad , Hipocampo , FN-kappa B/efectos de los fármacos , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/efectos de los fármacos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Estrés Psicológico/tratamiento farmacológico , Estrés Psicológico/metabolismo , Receptores de Glucocorticoides/efectos de los fármacos
9.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(2): 257-262, 2023 Mar.
Artículo en Chino | MEDLINE | ID: mdl-36949682

RESUMEN

The intestinal barrier, a complex structure consisting of multiple layers of defense barriers, blocks the transfer of intestinal and foreign bacteria and their metabolites into the internal environment of the human body. Intestinal permeability can be used to evaluate the integrity of the intestinal barrier. Increased intestinal permeability has been observed in patients with depressive disorder. Some studies have reported an interaction between depressive disorder and intestinal barrier. Herein, we reviewed reported findings on the mechanisms of how systematic low-grade inflammation, vagal nerve dysfunction, and hypothalamic-pituitary-adrenal axis dysfunction cause changes in intestinal permeability in patients with depressive disorder and the pathogenic mechanism of how bacterial translocation caused by damaged intestinal barrier leads to depressive disorder. In addition, the potential mechanisms of how antidepressants improve intestinal permeability and how probiotics improve depressive disorder have been discussed.


Asunto(s)
Trastorno Depresivo , Sistema Hipotálamo-Hipofisario , Humanos , Sistema Hipófiso-Suprarrenal , Intestinos/microbiología , Permeabilidad , Trastorno Depresivo/metabolismo , Trastorno Depresivo/patología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Mucosa Intestinal/patología
10.
Int J Mol Sci ; 24(4)2023 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-36834953

RESUMEN

The brain-derived neurotrophic factor (BDNF) is an extensively studied neurotrophin es sential for both developing the brain and maintaining adult brain function. In the adult hippocampus, BDNF is critical for maintaining adult neurogenesis. Adult hippocampal neurogenesis is involved not only in memory formation and learning ability, but also mood regulation and stress responses. Accordingly, decreased levels of BDNF, accompanied by low levels of adult neurogenesis, occurs in brains of older adults with impaired cognitive function and in those of patients with major depression disorder. Therefore, elucidating the mechanisms that maintain hippocampal BDNF levels is biologically and clinically important. It has been revealed that signalling from peripheral tissues contribute to the regulation of BDNF expression in the brain across the blood-brain barrier. Moreover, recent studies indicated evidence that neuronal pathways can also be a mechanism by which peripheral tissues signal to the brain for the regulation of BDNF expression. In this review, we give an overview of the current status in the regulation of central BDNF expression by peripheral signalling, with a special interest in the regulation of hippocampal BDNF levels by signals via the vagus nerve. Finally, we discuss the relationship between signalling from peripheral tissues and age-associated control of central BDNF expression.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo , Sistema Nervioso Periférico , Nervio Vago , Anciano , Humanos , Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Trastorno Depresivo/metabolismo , Hipocampo/metabolismo , Aprendizaje , Sistema Nervioso Periférico/metabolismo , Nervio Vago/metabolismo
11.
J Affect Disord ; 320: 98-107, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-36162674

RESUMEN

BACKGROUND: Although the Wistar Kyoto (WKY) rat has been consistently recognized as an animal model with endogenous depression, the exact molecular mechanisms underlying its genetic susceptibility to depression remain undetermined. METHODS: Compared with the Wistar rats, the depression-like behaviors of the male WKY ones were evaluated by both the sucrose preference test and forced swimming test. Golgi staining analysis was conducted to access the dendritic morphology. TMT-labelled quantitative proteomics analyses were respectively performed in the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), and hippocampus (Hip), followed by KEGG enrichment-based clustering analysis, Venn diagram analysis, and Pearson correlation analysis. RESULTS: The WKY strain showed significant differences in both the depression-like behaviors and synaptic plasticity. Moreover, the WKY model displayed markedly distinct differentially-expressed protein (DEP) profiles, with minor differences between the WKY subgroups. A cerebral regional commonality and specificity were evident in the signaling pathways enriched in the WKY model, and a total of 15 brain region-specific DEPs were identified to closely correlate with the depression-like phenotypes (in the mPFC: Lrrc8d, Dcun1d2, and Mtnd5; in the NAc: Ccdc154, Sec14l2, Kif2a, LOC680322, Me1, Mknk1, and Ret7; in the Hip: Sec14l2, Serpinf2, LOC103694855, Fam13c, and Loxl1). Data were available via ProteomeXchange with identifier PXD029079. LIMITATIONS: Female WKY rats are not included, and the roles of these candidate DEPs in depression remain further elucidation. CONCLUSION: The present study further evidences the brain region-specific protein signatures in the male WKY model with endogenous depression, providing novel insights into the pathogenesis of depression in males.


Asunto(s)
Trastorno Depresivo , Proteómica , Animales , Ratas , Masculino , Femenino , Ratas Endogámicas WKY , Trastorno Depresivo/genética , Trastorno Depresivo/metabolismo , Encéfalo/metabolismo , Ratas Wistar , Modelos Animales de Enfermedad , Depresión/genética
12.
Int J Mol Sci ; 23(21)2022 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-36362016

RESUMEN

Studies suggest that astrocytic connexins (Cx) have an important role in the regulation of high brain functions through their ability to establish fine-tuned communication with neurons within the tripartite synapse. In light of these properties, growing evidence suggests a role of Cx in psychiatric disorders such as major depression but also in the therapeutic activity of antidepressant drugs. However, the real impact of Cx on treatment response and the underlying neurobiological mechanisms remain yet to be clarified. On this ground, the present study was designed to evaluate the functional activity of Cx in a mouse model of depression based on chronic corticosterone exposure and to determine to which extent their pharmacological inactivation influences the antidepressant-like activity of venlafaxine (VENLA). On the one hand, our results indicate that depressed mice have impaired Cx-based gap-junction and hemichannel activities. On the other hand, while VENLA exerts robust antidepressant-like activity in depressed mice; this effect is abolished by the pharmacological inhibition of Cx with carbenoxolone (CBX). Interestingly, the combination of VENLA and CBX is also associated with a higher rate of relapse after treatment withdrawal. To our knowledge, this study is one of the first to develop a model of relapse, and our results reveal that Cx-mediated dynamic neuroglial interactions play a critical role in the efficacy of monoaminergic antidepressant drugs, thus providing new targets for the treatment of depression.


Asunto(s)
Astrocitos , Conexinas , Trastorno Depresivo , Animales , Ratones , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Carbenoxolona/farmacología , Conexinas/efectos de los fármacos , Conexinas/metabolismo , Fenotipo , Recurrencia , Depresión/tratamiento farmacológico , Depresión/metabolismo , Trastorno Depresivo/tratamiento farmacológico , Trastorno Depresivo/metabolismo
13.
Int J Mol Sci ; 23(19)2022 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-36232725

RESUMEN

Depressive disorders (DDs) are an increasingly common health problem that affects all age groups. DDs pathogenesis is multifactorial. However, it was proven that stress is one of the most important environmental factors contributing to the development of these conditions. In recent years, there has been growing interest in the role of the glutamatergic system in the context of pharmacotherapy of DDs. Thus, it has become increasingly important to explore the functioning of excitatory synapses in pathogenesis and pharmacological treatment of psychiatric disorders (including DDs). This knowledge may lead to the description of new mechanisms of depression and indicate new potential targets for the pharmacotherapy of illness. An excitatory synapse is a highly complex and very dynamic structure, containing a vast number of proteins. This review aimed to discuss in detail the role of the key postsynaptic proteins (e.g., NMDAR, AMPAR, mGluR5, PSD-95, Homer, NOS etc.) in the excitatory synapse and to systematize the knowledge about changes that occur in the clinical course of depression and after antidepressant treatment. In addition, a discussion on the potential use of ligands and/or modulators of postsynaptic proteins at the excitatory synapse has been presented.


Asunto(s)
Trastorno Depresivo , Sinapsis , Encéfalo/metabolismo , Trastorno Depresivo/tratamiento farmacológico , Trastorno Depresivo/metabolismo , Homólogo 4 de la Proteína Discs Large/metabolismo , Humanos , Ligandos , Sinapsis/metabolismo
14.
Proc Natl Acad Sci U S A ; 119(33): e2117903119, 2022 08 16.
Artículo en Inglés | MEDLINE | ID: mdl-35939697

RESUMEN

Dopamine D1 receptors (D1Rs) in the hippocampal dentate gyrus (DG) are essential for antidepressant effects. However, the midbrain dopaminergic neurons, the major source of dopamine in the brain, only sparsely project to DG, suggesting possible activation of DG D1Rs by endogenous substances other than dopamine. We have examined this possibility using electrophysiological and biochemical techniques and found robust activation of D1Rs in mouse DG neurons by noradrenaline. Noradrenaline at the micromolar range potentiated synaptic transmission at the DG output and increased the phosphorylation of protein kinase A substrates in DG via activation of D1Rs and ß adrenergic receptors. Neuronal excitation preferentially enhanced noradrenaline-induced synaptic potentiation mediated by D1Rs with minor effects on ß-receptor-dependent potentiation. Increased voluntary exercise by wheel running also enhanced noradrenaline-induced, D1R-mediated synaptic potentiation, suggesting a distinct functional role of the noradrenaline-D1R signaling. We then examined the role of this signaling in antidepressant effects using mice exposed to chronic restraint stress. In the stressed mice, an antidepressant acting on the noradrenergic system induced a mature-to-immature change in the DG neuron phenotype, a previously proposed cellular substrate for antidepressant action. This effect was evident only in mice subjected to wheel running and blocked by a D1R antagonist. These results suggest a critical role of noradrenaline-induced activation of D1Rs in antidepressant effects in DG. Experience-dependent regulation of noradrenaline-D1R signaling may determine responsiveness to antidepressant drugs in depressive disorders.


Asunto(s)
Giro Dentado , Trastorno Depresivo , Dopamina , Neuronas Dopaminérgicas , Norepinefrina , Receptores de Dopamina D1 , Animales , Antidepresivos/farmacología , Giro Dentado/metabolismo , Trastorno Depresivo/metabolismo , Dopamina/metabolismo , Neuronas Dopaminérgicas/metabolismo , Ratones , Norepinefrina/metabolismo , Norepinefrina/farmacología , Receptores de Dopamina D1/metabolismo
15.
Neurosci Biobehav Rev ; 138: 104718, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35661753

RESUMEN

Adequate oxygen supply is essential for the human brain to meet its high energy demands. Therefore, elaborate molecular and systemic mechanism are in place to enable adaptation to low oxygen availability. Anxiety and depressive disorders are characterized by alterations in brain oxygen metabolism and of its components, such as mitochondria or hypoxia inducible factor (HIF)-pathways. Conversely, sensitivity and tolerance to hypoxia may depend on parameters of mental stress and the severity of anxiety and depressive disorders. Here we discuss relevant mechanisms of adaptations to hypoxia, as well as their involvement in mental stress and the etiopathogenesis of anxiety and depressive disorders. We suggest that mechanisms of adaptations to hypoxia (including metabolic responses, inflammation, and the activation of chemosensitive brain regions) modulate and are modulated by stress-related pathways and associated psychiatric diseases. While severe chronic hypoxia or dysfunctional hypoxia adaptations can contribute to the pathogenesis of anxiety and depressive disorders, harnessing controlled responses to hypoxia to increase cellular and psychological resilience emerges as a novel treatment strategy for these diseases.


Asunto(s)
Trastorno Depresivo , Hipoxia , Ansiedad , Trastorno Depresivo/metabolismo , Humanos , Hipoxia/metabolismo , Mitocondrias/metabolismo , Oxígeno/metabolismo
16.
J Immunol Res ; 2022: 6724881, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35615531

RESUMEN

Objective: The study is aimed at evaluating the immune-activation state before and after treatment in patients with first-episode depressive disorder (FDD) with evaluating the ILs and CRP levels and further clarifying the association between autoimmunity and the etiology and pathogenesis of FDD. Methods: We designed a case-control study. FDD patients and healthy subjects were enrolled in the FDD group and control group. Serum IL-6, IL-17, and CRP were measured before and after selective serotonin reuptake inhibitor (SSRI) therapy, as well as Hamilton rating scale for depression (HAMD) and life event scale (LES) scores. The correlations between IL-6 and IL-17 and HAMD and LES scores were analysed, and multiple linear regression analysis was performed for HAMD score. Results: 40 FDD patients and 40 healthy subjects were included in the FDD and control group from October 2009 to September 2012. Before treatment, the IL-6 (28.99 ± 5.51, P < 0.001) and IL-17 (41.15 ± 4.80, P < 0.001) in the FDD group were significantly higher than the control group (16.84 ± 3.78 and 21.68 ± 3.72, respectively). The C-reactive protein (CRP) level in two groups was comparable (P = 0.879). After treatment, the IL-6 (18.69 ± 5.07, P < 0.001) and IL-17 (30.67 ± 3.47, P < 0.001) levels and HAMD scores (6.73 ± 4.15) in the FDD group were significantly decreased than before treatment (P < 0.001, respectively). CRP level was slightly increased after treatment without statistically significant (P = 0.239). The HAMD score correlated with IL-6 (r = 0.638, P < 0.001) and IL-17 (r = 0.927, P < 0.001); the total LES and negative LES also correlated with IL-6 (r = 0.226, P < 0.05) (r = 0.366, P <0.001) and IL-17 (r = 0.348, P < 0.001) (r = 0.493, P < 0.001). Multiple linear regression analysis showed that both of the IL-6 and IL-17 had direct impact on HAMD score. Conclusion: The autoimmunity status was overactivated in FDD patients, and serum IL-6 and IL-17 levels had direct impact on the HAMD score. Patients who experienced more negative life events had higher activation level of autoimmunity status and HAMD scores, and serum IL-6 and IL-17 levels can be decreased by SSRI treatment.


Asunto(s)
Autoinmunidad , Trastorno Depresivo , Interleucina-17 , Interleucina-6 , Estudios de Casos y Controles , Depresión/etiología , Depresión/inmunología , Depresión/metabolismo , Trastorno Depresivo/etiología , Trastorno Depresivo/inmunología , Trastorno Depresivo/metabolismo , Humanos , Interleucina-17/sangre , Interleucina-17/metabolismo , Interleucina-6/sangre , Interleucina-6/metabolismo
17.
Nutrients ; 14(9)2022 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-35565888

RESUMEN

The role of gut microbiota and its association with the central nervous system via the microbiome-brain-gut axis has been widely discussed in the literature. The aim of this review is to investigate the impact of gut microbiota on the development of depression and underlying molecular mechanisms. There are two possible pathways in which this interaction might occur. The first one suggests that depressive disorder could lead to dysbiosis and one of the causes may be the influence on the hypothalamic-pituitary-adrenal (HPA) axis. The second one considers if changes in the composition of gut microbiota might cause depressive disorder. The mechanisms that could be responsible for this interaction include the secretion of neurotransmitters, gut peptides and the activation of the immune system. However, current knowledge on this topic does not allow for us to state an unambiguous conclusion, and future studies that take into consideration more precise stress-measurement methods are needed to further explore direct mechanisms of the interaction between gut microbiota and mental health.


Asunto(s)
Trastorno Depresivo , Microbioma Gastrointestinal , Encéfalo/metabolismo , Eje Cerebro-Intestino , Trastorno Depresivo/metabolismo , Disbiosis/metabolismo , Microbioma Gastrointestinal/fisiología , Humanos , Sistema Hipófiso-Suprarrenal/metabolismo
18.
Biochem Biophys Res Commun ; 593: 57-64, 2022 02 19.
Artículo en Inglés | MEDLINE | ID: mdl-35063770

RESUMEN

Some of the statins have been shown to have antidepressant effects, but whether atorvastatin (AV) has antidepressant effects is unknown. This study was to investigate the effect of AV treatment on depressive behaviors. Herein, we show that AV treatment had antidepressant-like effect in physiological conditions and antidepressant effect in depressive state which depended on α7 nicotinic acetylcholine receptor (α7nAChR) expression in the ventral hippocampus (vHPC), but not α4ß2 nicotinic acetylcholine receptor (α4ß2nAchR) expression in vHPC, nor the α7nAChR and α4ß2nAchR expression in dorsal hippocampus (dHPC). By using MLA, a selective α7nAChR antagonist, we investigated the role of α7nAChR in AV treatment. Behavior tests demonstrated that MLA abolished the antidepressant effect of AV. Besides, our data showed that AV treatment increased Akt phosphorylation, brain-derived neurotrophic factor (BDNF), synaptic related protein synapsin and spinophilin expression. The phosphatidylinositol-3 kinase (PI3K) inhibitor LY294002 reversed AV-induced increase of BDNF expression, newborn neurons and antidepressant behavior effects. Our study suggests that AV plays an antidepressant role by regulating synaptic plasticity of vHPC through PI3K/Akt-BDNF signaling pathway, which may be a good choice for depression treatment.


Asunto(s)
Antidepresivos/farmacología , Atorvastatina/farmacología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Trastorno Depresivo/prevención & control , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptor Nicotínico de Acetilcolina alfa 7/metabolismo , Animales , Anticolesterolemiantes/farmacología , Factor Neurotrófico Derivado del Encéfalo/genética , Trastorno Depresivo/etiología , Trastorno Depresivo/metabolismo , Trastorno Depresivo/patología , Regulación de la Expresión Génica , Masculino , Ratones , Ratones Endogámicos C57BL , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , Receptor Nicotínico de Acetilcolina alfa 7/genética
19.
J Biosci ; 472022.
Artículo en Inglés | MEDLINE | ID: mdl-35092409

RESUMEN

Depression is characterized by indifferent and slow thinking, leading to highly unfavorable social and economic burden. Hydroxysafflor yellow A (HSYA) is a traditional Chinese medicine and has many pharmacological properties, such as anti-oxidative and anti-inflammatory activities. However, the underlying mechanism unraveling the effect of HSYA on depression is still unclear. Here, depression animal model was established. It was demonstrated that HSYA improved depressive behavior in rat model of depression, which increased horizontal movement, vertical movement, sucrose percent index and decreased immobility of depressed rats. Moreover, HSYA inhibited the activation of HPA signaling, inflammation and oxidative stress in brain of depressed rats. HSYA played an opposite effect on production of chronic unpredicted mild stress (CUMS)-induced pro-inflammatory cytokines (TNF-α, IL-6 and IL-1ß). CUMS increased MDA expression but decreased SOD and GSH-Px expression, which were reversed by HSYA treatment. Furthermore, HSYA exerted a suppressive role in TLR4/NF-jB signaling pathway in brain of depressed rats. In conclusion, these findings indicted that HSYA can improve depressive behavior through inhibiting HPA signaling, repressing hippocampal inflammation and oxidative stress, which will provide a new therapeutic method for treating depression.


Asunto(s)
Chalcona/análogos & derivados , Trastorno Depresivo/tratamiento farmacológico , Encefalitis/tratamiento farmacológico , Hipocampo/efectos de los fármacos , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Quinonas/farmacología , Animales , Antiinflamatorios no Esteroideos/farmacología , Chalcona/farmacología , Citocinas/metabolismo , Trastorno Depresivo/metabolismo , Modelos Animales de Enfermedad , Encefalitis/metabolismo , Hipocampo/metabolismo , Hipocampo/fisiopatología , Masculino , FN-kappa B/metabolismo , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Ratas Wistar , Receptor Toll-Like 4/metabolismo
20.
Cell ; 185(1): 1-3, 2022 01 06.
Artículo en Inglés | MEDLINE | ID: mdl-34995512

RESUMEN

Psychiatric disease is one of the greatest health challenges of our time. The pipeline for conceptually novel therapeutics remains low, in part because uncovering the biological mechanisms of psychiatric disease has been difficult. We asked experts researching different aspects of psychiatric disease: what do you see as the major urgent questions that need to be addressed? Where are the next frontiers, and what are the current hurdles to understanding the biological basis of psychiatric disease?


Asunto(s)
Antidepresivos/uso terapéutico , Ciencia de los Datos/métodos , Depresión/tratamiento farmacológico , Depresión/metabolismo , Trastorno Depresivo/tratamiento farmacológico , Trastorno Depresivo/metabolismo , Genómica/métodos , Medicina de Precisión/métodos , Investigación Biomédica Traslacional/métodos , Animales , Depresión/genética , Trastorno Depresivo/genética , Humanos , Neuronas/metabolismo , Corteza Prefrontal/metabolismo , Resultado del Tratamiento
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