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1.
Mol Neurobiol ; 2024 May 04.
Article in English | MEDLINE | ID: mdl-38703344

ABSTRACT

Major depressive disorder (MDD) is a severe disorder that causes enormous loss of quality of life, and among the factors underlying MDD is stress in maternal deprivation (MD). In addition, classic pharmacotherapy has presented severe adverse effects. Centella asiatica (C. asiatica) demonstrates a potential neuroprotective effect but has not yet been evaluated in MD models. This study aimed to evaluate the effect of C. asiatica extract and the active compound madecassic acid on possible depressive-like behavior, inflammation, and oxidative stress in the hippocampus and serum of young rats submitted to MD in the first days of life. Rats (after the first day of birth) were separated from the mother for 3 h a day for 10 days. When adults, these animals were divided into groups and submitted to treatment for 14 days. After subjecting the animals to protocols of locomotor activity in the open field and behavioral despair in the forced swimming test, researchers then euthanized the animals. The hippocampus and serum were collected and analyzed for the inflammatory cytokines and oxidative markers. The C. asiatica extract and active compound reversed or reduced depressive-like behaviors, inflammation in the hippocampus, and oxidative stress in serum and hippocampus. These results suggest that C. asiatica and madecassic acid have potential antidepressant action, at least partially, through anti-inflammatory and antioxidant profiles.

2.
Basic Clin Pharmacol Toxicol ; 134(5): 563-573, 2024 May.
Article in English | MEDLINE | ID: mdl-38459754

ABSTRACT

Dementia is an umbrella term for a broad group of age-associated neurodegenerative diseases. It is estimated that dementia affects 50 million people worldwide and that Alzheimer's disease (AD) is responsible for up to 75% of cases. Small extracellular senile plaques composed of filamentous aggregates of amyloid ß (Aß) protein tend to bind to neuronal receptors, affecting cholinergic, serotonergic, dopaminergic and noradrenergic neurotransmission, leading to neuroinflammation, among other pathophysiologic processes and subsequent neuronal death, followed by dementia. The amyloid cascade hypothesis points to a pathological process in the cleavage of the amyloid precursor protein (APP), resulting in pathological Aß. There is a close relationship between the pathologies that lead to dementia and depression. It is estimated that depression is prevalent in up to 90% of individuals diagnosed with Parkinson's disease, with varying severity, and in 20 to 30% of cases of Alzheimer's disease. The hypothalamic pituitary adrenal (HPA) axis is the great intermediary between the pathophysiological mechanisms in neurodegenerative diseases and depression. This review discusses the role of Aß protein in the pathophysiological mechanisms of dementia and depression, considering the HPA axis, neuroinflammation, oxidative stress, signalling pathways and neurotransmission.


Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Dementia , Neurodegenerative Diseases , Humans , Alzheimer Disease/pathology , Amyloid beta-Peptides/metabolism , Depression , Hypothalamo-Hypophyseal System/metabolism , Hypothalamo-Hypophyseal System/pathology , Neuroinflammatory Diseases , Pituitary-Adrenal System/metabolism , Pituitary-Adrenal System/pathology , Dementia/metabolism
3.
Mol Neurobiol ; 2024 Feb 03.
Article in English | MEDLINE | ID: mdl-38307968

ABSTRACT

Early life stress (ELS), characterized as abuse, neglect, and abandonment, can cause several adverse consequences in the lives of affected individuals. ELS experiences can affect an individual's development in variable ways, persisting in the long term and promoting lasting impacts, considering that early exposure to stressors can be biologically incorporated, as prolonged stimulation of stress response systems affects the development of the brain structure and other body systems, increasing the risk of diseases associated with stress and cognitive impairment. This type of stress increases the risk of developing major depressive disorder (MDD) in a severe form that does not respond adequately to traditional antidepressant treatments. Several alterations are studied as mechanisms that relate ELS with MDD, such as epigenetic alterations, neurotransmitters, and neuronal signaling. This review discusses research that brings evidence about the ELS mechanisms involved in synaptic impairments and MDD. The processes involved in epigenetic changes and the HPA axis are highlighted, as well as changes in neurotransmitters and neuronal signaling mechanisms.

4.
Mol Neurobiol ; 2023 Dec 20.
Article in English | MEDLINE | ID: mdl-38123701

ABSTRACT

Although many efforts have been made to understand the pathophysiological mechanisms of COVID-19, critical gaps remain to be explored. This study aimed to investigate potential alterations in adipokine levels (specifically adiponectin, leptin, and resistin) among individuals with COVID-19. Within this population, we further assessed the association between these markers with both, body mass index (BMI) and psychiatric symptoms. This cross-sectional study included an age- and sex-matched sample of adults with COVID-19 (cases) and without COVID-19 (controls). We evaluated the severity of psychiatric symptoms, BMI, and adipokines. Individuals with COVID-19 presented greater BMI, stress levels, and leptin levels when compared to controls. Leptin levels were greater in individuals with moderate/severe COVID-19 as compared to individuals with COVID-19 who were asymptomatic or having mild symptoms. Leptin levels were positively correlated with BMI, severity of depressive and anxiety symptoms, and stress levels in the total sample. Leptin levels were also positively correlated with BMI, severity of anxiety symptoms, and stress levels in controls. In cases, there was a positive correlation between adiponectin and the severity of depressive symptoms and stress levels and leptin/resistin with BMI. A linear regression model revealed that BMI, severity of anxiety symptoms, and the diagnosis of COVID-19 are independently associated with increased leptin levels. Thus, leptin levels seem to be impacted by the COVID-19 infection, anxiety, and BMI.

5.
Brain Sci ; 13(10)2023 Oct 05.
Article in English | MEDLINE | ID: mdl-37891783

ABSTRACT

The COVID-19 pandemic generated, in addition to severe symptoms, hospitalizations and deaths worldwide, as well as stress from the fear of the disease and social uncertainties, from restriction measures and social isolation. Stress from social isolation impacts mental health, aggravating existing conditions and triggering neuropsychiatric symptoms in individuals with biopsychosocial vulnerability. During and immediately after the period of social restriction imposed by the pandemic, the scientific community carried out several research protocols. These revealed results that relevantly demonstrate the harmful effect of the stress induced by the pandemic situation. This narrative review reports and discusses research results demonstrating impairments in psychiatric disorders such as autism spectrum disorder, dementia, eating disorders, schizophrenia, anxiety, and depression. In this sense, the community has identified a significant negative influence of social isolation on the mental health of individuals through the modification of individual routines and the absence of social interactions. Moreover, the community identified perceived differences related to the impacts on men and women. In addition to studies showing the effect of social isolation on disorders, an evaluation of protocols with some possible therapeutic intervention strategies during times of social restriction was developed.

6.
Metab Syndr Relat Disord ; 21(6): 335-344, 2023 08.
Article in English | MEDLINE | ID: mdl-37352417

ABSTRACT

Background and Aims: To evaluate the effect of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus on the function and metabolic changes, as well as the relationship of the virus with blood groups. Methods and Results: This cross-sectional study included a matched sample of adult individuals with coronavirus disease 2019 (COVID-19) (n = 114) or without (controls; n = 236). Blood samples were collected and processed for triglycerides (TGs), total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, and blood typing analysis. The results showed that subjects with COVID-19 had higher TG and lower HDL-C levels compared with the control group. As for blood typing, the risk of COVID-19 was higher in subjects with blood group A than in those with blood group B and in those with other blood groups. In addition, an association of COVID-19 with blood type and Rh A- was observed. When related to the severity of COVID-19 symptoms, blood type A was more protective against moderate/severe symptoms compared with blood type O. In addition, individuals with blood type O were 2.90 times more likely to have symptoms moderate/severe symptoms of COVID-19 than those with other blood groups and individuals with type A blood were less likely to have severe/moderate symptoms of COVID-19 compared with individuals without type A blood. Conclusion: The results suggest that blood type may play a role in susceptibility to SARS-CoV-2 infection and add evidence that infection with the novel coronavirus may be associated with changes in lipid metabolism.


Subject(s)
Blood Grouping and Crossmatching , COVID-19 , Humans , Triglycerides/blood , SARS-CoV-2 , Cholesterol, HDL/blood , Blood Group Antigens , Cross-Sectional Studies , Case-Control Studies
7.
J Affect Disord ; 330: 216-226, 2023 06 01.
Article in English | MEDLINE | ID: mdl-36907459

ABSTRACT

BACKGROUND: Although many studies have pointed out a possible relationship between COVID-19 and the presence of psychiatric disorders, the majority of the studies have significant limitations. This study investigates the influence of COVID-19 infection on mental health. METHODS: This cross-sectional study included an age- and sex-matched sample of adult individuals positive (cases) or negative (controls) for COVID-19. We evaluated the presence of psychiatric conditions and C-reactive protein (CRP). RESULTS: Findings showed greater severity of depressive symptoms, higher levels of stress, and greater CRP in cases. The severity of depressive and insomnia symptoms, as well as the CRP were more remarkable in individuals with moderate/severe COVID-19. We found a positive correlation between stress and severity of anxiety, depression, and insomnia in individuals with or without COVID-19. There was a positive correlation between CRP levels and severity of depressive symptoms in cases and controls, and a positive correlation between CRP levels and the severity of anxiety symptoms and stress levels only in individuals with COVID-19. Individuals with COVID-19 and depression had greater CRP than those with COVID-19 without current major depressive disorder. LIMITATIONS: We cannot infer causality because this is a cross-sectional study, and the majority of COVID-19 sample was asymptomatic or had mild symptoms, which may limit the generalizability of our findings for moderate/severe cases. CONCLUSIONS: Individuals with COVID-19 showed greater severity of psychological symptoms, which may impact on the development of psychiatric disorders in the future. CPR seem to be a promising biomarker for earlier detection of post-COVID depression.


Subject(s)
COVID-19 , Depressive Disorder, Major , Sleep Initiation and Maintenance Disorders , Adult , Humans , C-Reactive Protein/metabolism , Cross-Sectional Studies , Depression/psychology , Anxiety/epidemiology , Anxiety/psychology , Stress, Psychological/psychology
8.
Adv Exp Med Biol ; 1411: 163-190, 2023.
Article in English | MEDLINE | ID: mdl-36949310

ABSTRACT

Major depressive disorder (MDD) is one of the most prevalent disorders and causes severe damage to people's quality of life. Lifelong stress is one of the major villains in triggering MDD. Studies have shown that both stress and MDD, especially the more severe conditions of the disorder, are associated with inflammation and neuroinflammation and the relationship to an imbalance in tryptophan metabolism towards the kynurenine pathway (KP) through the enzymes indoleamine-2,3-dioxygenase (IDO), which is mainly stimulated by pro-inflammatory cytokines and tryptophan-2,3-dioxygenase (TDO) which is activated primarily by glucocorticoids. Considering that several pathophysiological mechanisms of MDD underlie or interact with biological processes from KP metabolites, this chapter addresses and discusses the function of these mechanisms. Activities triggered by stress and the hypothalamic-pituitary-adrenal (HPA) axis and immune and inflammatory processes, in addition to epigenetic phenomena and the gut-brain axis (GBA), are addressed. Finally, studies on the function and mechanisms of physical exercise in the KP metabolism and MDD are pointed out and discussed.


Subject(s)
Depressive Disorder, Major , Dioxygenases , Humans , Kynurenine/metabolism , Tryptophan/metabolism , Quality of Life , Inflammation/metabolism
9.
Naunyn Schmiedebergs Arch Pharmacol ; 396(7): 1423-1433, 2023 07.
Article in English | MEDLINE | ID: mdl-36735044

ABSTRACT

Major depressive disorder (MDD) etiology is still not completely understood, and many individuals resist the traditional treatments. Chronic exposure to stressful events can contribute to development and progression and be involved in biological changes underlying MDD. Among the biological mechanisms involved, inflammatory changes and oxidative balance are associated with MDD pathophysiology. Quetiapine, a second-generation antipsychotic, induces a better therapeutic response in individuals refractory to traditional treatments. The main objectives of this research were as follows: to evaluate the effect of chronic mild stress (CMS) on depressive-like behaviors, oxidative stress, and inflammation in adult rats; to evaluate the possible antidepressant, antioxidant, and anti-inflammatory effects of quetiapine. The animals were submitted to CMS protocols. At the end of the CMS, the animals were submitted to a chronic treatment for 14 days with the following drugs: quetiapine (20 mg/kg), imipramine (30 mg/kg), and escitalopram (10 mg/kg). At the end of the treatments, the animals were evaluated in the open field tests, anhedonia (splash test), and forced swimming. The animals were euthanized after the behavioral tests, and serum samples were collected. Myeloperoxidase (MPO) activity and interleukin-6 (IL-6) levels were analyzed. CMS induced an increase in depressive-like behaviors, and quetiapine significantly reduced these behaviors. MPO activity and IL-6 levels increased in the serum of animals submitted to CMS. Quetiapine significantly reduced MPO activity and IL-6 levels. These results corroborate other evidence, indicating that chronic stress is a relevant phenomenon in the etiology of depression and suggesting that quetiapine induces an antidepressant effect because it reduces oxidative and inflammatory mechanisms.


Subject(s)
Depressive Disorder, Major , Rats , Animals , Quetiapine Fumarate/pharmacology , Quetiapine Fumarate/therapeutic use , Depressive Disorder, Major/drug therapy , Interleukin-6 , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Depression/drug therapy , Oxidative Stress , Behavior, Animal , Inflammation/drug therapy , Stress, Psychological/drug therapy , Disease Models, Animal
10.
Cell Mol Neurobiol ; 43(2): 621-637, 2023 Mar.
Article in English | MEDLINE | ID: mdl-35348977

ABSTRACT

Neuroinflammation is closely related to the development of depression, since the latter is caused, among other factors, by inflammatory processes, mainly related to the activation of microglia and expression of specific genes, which occurs during the neuroinflammatory process. Thus, COVID-19 is an important risk factor for the development of depression, since in addition to generating the feeling of stress, which also increases the activity of the immune system, it is also the cause of pathological processes and physiological ones that lead to the development of neuroinflammation, microglial activation, gene expression dysfunction and decreased concentration of available serotonin. That said, drugs are being used to combat COVID-19 to reduce the oxidative stress presented in the disease. Thus, tramadol and fluoxetine are highlighted as drugs used, however, although they present some positive results, such as the reduction of pro-inflammatory cytokines, they are also associated with negative effects such as dependence, pulmonary, cardiac and brain impairment. From this, the purinergic system is highlighted in the literature as a possible therapeutic target. This is because its mechanisms are related to the regulation of microglia, astrocytes and the physiology of important neurotransmitters and hormones. Added to this, there is a modulation of inflammatory activity, especially with regard to the P2X7 receptors of this system. The latter is an important target for the treatment of depression and COVID-19, since positive results were obtained through the genetic exclusion of this receptor and the use of selective antagonists.


Subject(s)
COVID-19 , Depressive Disorder, Major , Humans , Depressive Disorder, Major/metabolism , Neuroinflammatory Diseases , COVID-19/metabolism , Brain/metabolism , Cytokines/metabolism , Microglia/metabolism , Receptors, Purinergic P2X7/metabolism
11.
J Mol Neurosci ; 72(6): 1166-1181, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35322375

ABSTRACT

COVID-19 is associated with oxidative stress, peripheral hyper inflammation, and neuroinflammation, especially in individuals with a more severe form of the disease. Some studies provide evidence on the onset or exacerbation of major depressive disorder (MDD), among other psychiatric disorders due to COVID-19. Oxidative stress and neuroinflammation are associated conditions, especially in the more severe form of MDD and in refractoriness to available therapeutic strategies. Inflammatory cytokines in the COVID-19 hyper inflammation process can activate the hypothalamic-pituitary-adrenal (HPA) axis and the indoleamine-2,3-dioxygenase (IDO) enzyme. IDO activation can reduce tryptophan and increase toxic metabolites of the kynurenine pathway, which increases glial activation, neuroinflammation, toxicity, and neuronal death. This review surveyed a number of studies and analyzed the mechanisms of oxidative stress, inflammation, and neuroinflammation involved in COVID-19 and depression. Finally, the importance of more protocols that can help elucidate the interaction between these mechanisms underlying COVID-19 and MDD and the possible therapeutic strategies involved in the interaction of these mechanisms are highlighted.


Subject(s)
COVID-19 , Depressive Disorder, Major , Depression , Depressive Disorder, Major/drug therapy , Humans , Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism , Inflammation , Kynurenine/metabolism , Kynurenine/therapeutic use , Neuroinflammatory Diseases , Oxidative Stress
12.
J Mol Med (Berl) ; 100(4): 645-663, 2022 04.
Article in English | MEDLINE | ID: mdl-35249135

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has significantly impacted the world and has driven many researchers into the pathophysiology of COVID-19. In the findings, there is a close association between purinergic signaling and the immune response. Then, this study aimed to evaluate alterations in the purinergic signaling in COVID-19 patients according to range severity. We divided the COVID-19 patients into moderate and severe cases following the guideless of NIH and WHO, together with clinical characteristics. The blood samples were collected to obtain PBMCs and platelets. We analyzed the ectonucleotidase activities through ATP, ADP, AMP, Ado hydrolysis, E-NTPDase1 (CD39), and 5'-NT (CD73) expression by flow cytometry in total leukocytes. The extracellular ATP was measured by bioluminescence, and cytokines were analyzed by flow cytometry. We observed a decrease in ATP hydrolysis and increased AMP hydrolysis in PBMCs for both groups. In severe cases, ATP hydrolysis was raised for the platelets, while ADP and AMP hydrolysis have risen significantly in both groups. Additionally, there was a significant increase in ADP hydrolysis in severe cases compared to moderate cases. In addition, we observed an increase in the ADA activity in platelets of moderate patients. Moderate and severe cases showed increased expression of CD39 and CD73 in total leukocytes. To finalize the purinergic signaling, extracellular ATP was increased in both groups. Furthermore, there was an increase in IL-2, IL-6, IL-10, and IL-17 in moderate and severe groups. Thus, for the first time, our findings confirm the changes in purinergic signaling and immune response in COVID-19, in addition to making it more evident that the severity range directly impacts these changes. Therefore, the therapeutic potential of the purinergic system must be highlighted and studied as a possible target for the treatment of SARS-CoV-2 disease. KEY MESSAGES: COVID-19 patients exhibit alterations in purinergic system and immune response. High levels of extracellular ATP lead to different inflammatory responses. CD39 and CD73 expression were increased in COVID-19 patients. Cytokines IL-2, IL-6, IL-10, and IL-17 also were altered in these patients. The purinergic system may be a possibility target to SARS-CoV-2 treatments.


Subject(s)
COVID-19 , Adenosine Triphosphate/metabolism , Blood Platelets , Humans , Pandemics , SARS-CoV-2
14.
Rev Neurosci ; 33(3): 227-255, 2022 04 26.
Article in English | MEDLINE | ID: mdl-34388328

ABSTRACT

Major depressive disorder (MDD) is one of the most prevalent and debilitating psychiatric disorders, with a large number of patients not showing an effective therapeutic response to available treatments. Several biopsychosocial factors, such as stress in childhood and throughout life, and factors related to biological aging, may increase the susceptibility to MDD development. Included in critical biological processes related to aging and underlying biological mechanisms associated with MDD is the shortening of telomeres and changes in telomerase activity. This comprehensive review discusses studies that assessed the length of telomeres or telomerase activity and function in peripheral blood cells and brain tissues of MDD individuals. Also, results from in vitro protocols and animal models of stress and depressive-like behaviors were included. We also expand our discussion to include the role of telomere biology as it relates to other relevant biological mechanisms, such as the hypothalamic-pituitary-adrenal (HPA) axis, oxidative stress, inflammation, genetics, and epigenetic changes. In the text and the discussion, conflicting results in the literature were observed, especially considering the size of telomeres in the central nervous system, on which there are different protocols with divergent results in the literature. Finally, the context of this review is considering cell signaling, transcription factors, and neurotransmission, which are involved in MDD and can be underlying to senescence, telomere shortening, and telomerase functions.


Subject(s)
Depressive Disorder, Major , Telomerase , Aging/genetics , Animals , Depressive Disorder, Major/genetics , Depressive Disorder, Major/therapy , Humans , Pituitary-Adrenal System/metabolism , Telomerase/genetics , Telomerase/metabolism , Telomere/genetics , Telomere/metabolism
15.
J. bras. psiquiatr ; 71(4): 296-302, 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1405465

ABSTRACT

ABSTRACT Objective: To identify the presence of burnout syndrome among nursing professionals in the emergency room and intensive care unit for adults of the University Hospital of Maringá. Methods: This is an exploratory and descriptive research study with a quantitative approach. It was developed by applying a questionnaire containing 22 questions from the Maslach Burnout Inventory instrument, which identifies the symptomatology dimensions of the burnout syndrome. Data analysis of the Maslach Burnout Inventory instrument was performed by adding up each dimension (Emotional Exhaustion, Depersonalization and Professional Fulfillment) of each questionnaire separately, according to the nursing professional's answers to each question. The values obtained were compared to the reference values of the Nucleus for Advanced Studies on Burnout Syndrome. Results: It was found that 31.36% of the nursing professionals at the University Hospital of Maringá emergency room had high Emotional Exhaustion, 30.92% had low Professional Fulfillment, and 39.25% had high Depersonalization. Regarding the nursing professionals in the Intensive Care Unit for Adults, 36.36% had high Emotional Exhaustion, 36.36% had low Professional Fulfillment, and 22.73% had high Depersonalization. Conclusion: The findings suggest that the Intensive Care Unit for Adults in the morning shift is the highest stressor and with a greater probability of the professionals developing burnout syndrome.


RESUMO Objetivo: Identificar a existência da síndrome de burnout entre os profissionais de enfermagem de pronto atendimento e unidade de terapia intensiva adulto do Hospital Universitário de Maringá. Métodos: Trata-se de pesquisa exploratória, descritiva e de abordagem quantitativa. O estudo foi desenvolvido por meio da aplicação de um questionário contendo 22 questões do instrumento Maslach Burnout Inventory, o qual identifica as dimensões sintomatológicas da síndrome de burnout. A análise dos dados do instrumento Maslach Burnout Inventory foi realizada por meio do somatório de cada dimensão (exaustão emocional, despersonalização e realização profissional) de cada questionário, separadamente, de acordo com as respostas que o profissional de enfermagem respondeu em cada questão. Os valores obtidos foram comparados com os valores de referência do Núcleo de Estudos Avançados sobre a Síndrome de Burnout. Resultados: Constatou-se que 31,36% dos profissionais de enfermagem do pronto atendimento do Hospital Universitário de Maringá apresentaram alta exaustão emocional, 30,92%, baixa realização profissional e 39,25%, alta despersonalização. Com relação aos profissionais de enfermagem da unidade de terapia intensiva adulto, 36,36% apresentaram alta exaustão emocional, 36,36%, baixa realização profissional e 22,73%, apresentaram alta despersonalização. Conclusão: Os resultados sugerem que o setor de unidade de terapia intensiva adulto do período matutino é o maior estressor e com maior probabilidade de os profissionais desenvolverem a síndrome de burnout.

16.
Behav Brain Res ; 406: 113226, 2021 05 21.
Article in English | MEDLINE | ID: mdl-33684423

ABSTRACT

Major depressive disorder (MDD) is one of the most prevalent forms of mental illness also affecting older adults. Recent evidence suggests a relationship between MDD and neurodegenerative diseases, including Parkinson's disease (PD). Individuals with PD have a predisposition to developing MDD, and both neurobiological conditions are associated with oxidative stress. Thus, we conducted this study to investigate depressive-like behavior and oxidative stress parameters using both animal models of PD and stress. Adult Wistar rats were subjected to chronic mild stress (CMS) protocol by 40 days and then it was used 6-hydroxydopamine (6-OHDA) as a model of PD, into the striatum. The experimental groups were: Control + Sham, Stress + Sham, Control+6-OHDA, and Stress+6-OHDA. Depressive like-behavior was evaluated by the forced swimming test (FST) and spontaneous locomotor activity by open-field test. Oxidative stress parameters were measured in the striatum, hippocampus, and prefrontal cortex (PFC). The results showed effects to increase immobility and decrease climbing times in the FST in Stress + Sham, Control+6-OHDA, and Stress+6-OHDA groups. The number of crossings and rearings were decreased in the Stress+6-OHDA group. The lipid peroxidation was increased in the PFC of Stress + Sham, and the hippocampus and striatum of Stress + Sham and Control+6-OHDA groups. Carbonyl protein levels increased in the PFC of Stress + Sham and striatum in Control+6-OHDA. Nitrite/Nitrate concentration was elevated in the PFC of Stress + Sham, in the hippocampus of Control+6-OHDA, the striatum of Stress + Sham, and Control+6-OHDA groups. Myeloperoxidase (MPO) activity was increased in the PFC and hippocampus of Stress + Sham and Control+6-OHDA groups. The activity of catalase decreased in the PFC of the Stress + Sham group. The activity of the superoxide dismutase (SOD) was decreased in the PFC of the Stress + Sham group, in the hippocampus of Stress + Sham and Control+6-OHDA groups, and the striatum of Control+6-OHDA group. These findings suggest that both stress and 6-OHDA induce depressive-like behavior and oxidative stress in the brain. The joining models have little evidence of the effects. Thus these findings suggest that other pathways are involved in the common point of the pathophysiology of PD and MDD.


Subject(s)
Adrenergic Agents/pharmacology , Behavior, Animal , Brain , Depressive Disorder, Major , Oxidative Stress , Oxidopamine/pharmacology , Parkinson Disease, Secondary , Stress, Psychological/complications , Animals , Behavior, Animal/drug effects , Behavior, Animal/physiology , Brain/drug effects , Brain/metabolism , Brain/physiopathology , Corpus Striatum/drug effects , Corpus Striatum/metabolism , Corpus Striatum/physiopathology , Depressive Disorder, Major/chemically induced , Depressive Disorder, Major/etiology , Depressive Disorder, Major/metabolism , Depressive Disorder, Major/physiopathology , Disease Models, Animal , Hippocampus/drug effects , Hippocampus/metabolism , Hippocampus/physiopathology , Male , Oxidative Stress/drug effects , Parkinson Disease, Secondary/chemically induced , Parkinson Disease, Secondary/etiology , Parkinson Disease, Secondary/metabolism , Parkinson Disease, Secondary/physiopathology , Prefrontal Cortex/drug effects , Prefrontal Cortex/metabolism , Prefrontal Cortex/physiopathology , Rats , Rats, Wistar
17.
Pharmacol Rep ; 73(2): 525-535, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33393059

ABSTRACT

BACKGROUND: Electroconvulsive therapy (ECT) is often recommended for major depressive disorder (MDD) for those who do not respond to the first and second antidepressant trials. A combination of two therapies could improve antidepressant efficacy. Thus, this study aimed to investigate the synergistic effects of ECT combined to antidepressants with a different mechanism of action. METHODS: Rats were treated once a day, for five days with ketamine (5 mg/kg), fluoxetine (1 mg/kg), and bupropion (4 mg/kg) alone or in combination with ECT (1 mA; 100 V). After, oxidative damage and antioxidant capacity were assessed in the prefrontal cortex (PFC) and hippocampus, and pro-inflammatory cytokines levels were evaluated in the serum. RESULTS: ECT alone increased lipid peroxidation in the PFC and hippocampus. In the PFC of rats treated with ECT in combination with fluoxetine and bupropion, and in the hippocampus of rats treated with ECT combined with ketamine and bupropion there was a reduction in the lipid peroxidation. The nitrite/nitrate was increased by ECT alone but reverted by combination with ketamine in the hippocampus. Superoxide dismutase (SOD) was increased by ECT and maintained by fluoxetine and bupropion in the PFC. ECT alone increased interleukin-1ß (IL-1ß) and the administration of ketamine was able to revert this increase showing a neuroprotective effect of this drug when in combination with ECT. CONCLUSION: The treatment with ECT leads to an increase in oxidative damage and alters the immunological system. The combination with ketamine was able to protect against oxidative damage and the immunological response induced by ECT.


Subject(s)
Antidepressive Agents/pharmacology , Electroconvulsive Therapy/adverse effects , Ketamine/pharmacology , Oxidative Stress/drug effects , Animals , Antidepressive Agents/administration & dosage , Bupropion/administration & dosage , Bupropion/pharmacology , Combined Modality Therapy , Depressive Disorder, Major/therapy , Electroconvulsive Therapy/methods , Fluoxetine/administration & dosage , Fluoxetine/pharmacology , Ketamine/administration & dosage , Male , Neuroprotective Agents/administration & dosage , Neuroprotective Agents/pharmacology , Rats , Rats, Wistar
18.
Mol Neurobiol ; 58(5): 1905-1916, 2021 May.
Article in English | MEDLINE | ID: mdl-33404981

ABSTRACT

Since December 2019, the world has been experiencing the challenge of facing coronavirus disease-19 (COVID-19), a severe infectious disease caused by the new coronavirus, SARS-CoV-2. The individuals with the most severe symptoms and the highest risk of death are the elderly and those with chronic illness. Among chronic conditions, those with a certain degree of chronic inflammation may predispose to a more severe evolution of COVID-19. Elderly with psychiatric disorders can present a persistent inflammatory state, a characteristic of the age's immunological senescence, but the disorder can accentuate that. Social isolation is still the safest way to avoid contamination. However, isolated older people may have or worsen mental health conditions due to isolation and health concerns. In this scenario, a SARS-CoV-2 infection may progress to more severe disease. Conversely, COVID-19 can predispose or aggravate psychiatric disorders, as it induces a cytokine storm, causing systemic hyper inflammation. It may damage the blood-brain barrier, resulting in inflammation in the central nervous system. Besides, SARS-CoV-2 is likely to reach and trigger an inflammatory process directly in the nervous system. This review makes an update about research on the mental health of the elderly during the pandemic. Also, it discusses the vulnerability of these individuals in the face of stress and in the case of contracting COVID-19, considering mainly the stress's hormonal and inflammatory mechanisms. Finally, the review points out possible care and attention strategies and entertainment and activities that can reduce the damage to mental and physical health and improve the elderly's quality of life. Graphical abstract Isolation and concerns about COVID-19 may harm elderly mental health. Immunosenescence and pandemic stress increase the risk of psychiatric disorders. Stress and disorders may potentiate the elderly's inflammation and COVID-19 symptoms. SARS-CoV-2 hyperinflammation is a risk factor for elderly psychiatric disorders.


Subject(s)
COVID-19/psychology , Mental Disorders/psychology , Mental Health , Quality of Life/psychology , Social Isolation/psychology , Aged , Aged, 80 and over , COVID-19/complications , Humans , Mental Disorders/complications , Pandemics
19.
Porto Alegre; Rede Unida; 20201222. 92 p.
Monography in Portuguese | LILACS | ID: biblio-1348428

ABSTRACT

Este livro se propõe a resgatar a sabedoria do povo indígena Kaingang na essência de suas práticas, pelo conhecimento de uma complexidade tão instigante, como são "as plantas que curam". Nossa proposta é contribuir para o fortalecimento desse conhecimento ainda presente junto às comunidades indígenas, apresentando um diálogo entre saber popular e científico, numa abordagem genuína sobre o uso das plantas medicinais pelos povos indígenas da etnia Kaingang, acrescido de uma rica contextualização científica, mantendo, todavia, o cuidado de não se apropriar ou "tomar" para si o legado originário. Propõe-se também a construir pontes com saberes milenares, passados de geração em geração, que outorgam autonomia e resistência aos povos indígenas, os quais, por fatores sociais e políticos diversos, vêem cada dia mais sua existência ameaçada. Compreende-se que essa sabedoria transcende até mesmo o plano científico, ampliando para uma compreensão cosmológica, a qual, de forma sistêmica, integra saber popular, cultura, religiosidades, mitos e conhecimento, contribuindo, sobretudo, para a constituição de uma territorialidade, que ancestralmente produz uma cultura de resistência junto aos povos indígenas. Enseja-se assim, uma singela contribuição a uma cultura que insiste em re-existir, numa relação que pode tornar-se muito fecunda quando assume um diálogo emancipador, práxico e potencializador de ambos os saberes, com produção de novas sínteses.


Subject(s)
Public Health , Integrality in Health , Indigenous Peoples , Medicine, Traditional
20.
Neurosci Biobehav Rev ; 86: 36-50, 2018 03.
Article in English | MEDLINE | ID: mdl-29288677

ABSTRACT

Major depressive disorder (MDD) is a highly debilitating condition that is drawing considerable attention due to its high global prevalence and to the fact that treatments are still far from reaching the total number of patients affected. Among available treatment strategies, quetiapine is an important research target, due to antidepressant responses in patients resistant to classical treatments and in animals submitted to protocols that induce depressive-like behaviours. Quetiapine has a broad spectrum of action, within which are many mechanisms that seem to be related to the most effective antidepressant therapeutic responses. In this review, research results related to the pharmacokinetic profile, neurotransmitters, receptors and signalling molecular targets involved in the functional and structural plasticity of key brain regions in MDD are reported and discussed. Moreover, the physiological mechanisms, which are targets of quetiapine and are involved in both MDD and poor therapeutic response, are reported. The main adverse effects observed from therapeutic dosages and overdose are also described. Finally, the main mechanisms underlying the therapeutic response are highlighted.


Subject(s)
Depressive Disorder, Major/drug therapy , Neuronal Plasticity/drug effects , Quetiapine Fumarate/therapeutic use , Animals , Antidepressive Agents/adverse effects , Antidepressive Agents/therapeutic use , Humans , Quetiapine Fumarate/adverse effects , Quetiapine Fumarate/pharmacology
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