Publications by authors named "Antônio Lúcio Teixeira"

428 Publications

Neurotrophic factors in systemic lupus erythematosus: markers of disease activity.

Clin Exp Rheumatol 2021 Jun 8. Epub 2021 Jun 8.

Department of Locomotor System, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

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June 2021

Low-dose candesartan prevents schizophrenia-like behavioral alterations in a neurodevelopmental two-hit model of schizophrenia.

Prog Neuropsychopharmacol Biol Psychiatry 2021 May 10;111:110348. Epub 2021 May 10.

Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil; National Institute for Translational Medicine (INCT-TM, CNPq), Ribeirão Preto, SP, Brazil. Electronic address:

Schizophrenia is a severe mental disorder with complex etiopathogenesis. Based on its neurodevelopmental features, an animal model induced by "two-hit" based on perinatal immune activation followed by peripubertal unpredictable stress was proposed. Sex influences the immune response, and concerning schizophrenia, it impacts the age of onset and symptoms severity. The neurobiological mechanisms underlying the influence of sex in schizophrenia is poorly understood. Our study aimed to evaluate sex influence on proinflammatory and oxidant alterations in male and female mice exposed to the two-hit model of schizophrenia, and its prevention by candesartan, an angiotensin II type 1 receptor (AT1R) blocker with neuroprotective properties. The two-hit model induced schizophrenia-like behavioral changes in animals of both sexes. Hippocampal microglial activation alongside the increased expression of NF-κB, and proinflammatory cytokines, namely interleukin (IL)-1β and TNF-α, were observed in male animals. Conversely, females presented increased hippocampal and plasma levels of nitrite and plasma lipid peroxidation. Peripubertal administration of low-dose candesartan (0.3 mg/kg PO) prevented behavioral, hippocampal, and systemic changes in male and female mice. While these results indicate the influence of sex on inflammatory and oxidative changes induced by the two-hit model, candesartan was effective in both males and females. The present study advances the neurobiological mechanisms underlying sex influence in schizophrenia and opens new avenues to prevent this devasting mental disorder.
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http://dx.doi.org/10.1016/j.pnpbp.2021.110348DOI Listing
May 2021

PI3K, mTOR and GSK3 modulate cytokines' production in peripheral leukocyte in temporal lobe epilepsy.

Neurosci Lett 2021 Jun 9;756:135948. Epub 2021 May 9.

Neuroscience Program, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Department of Pharmacology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. Electronic address:

Introduction: Epilepsy is a common pathological condition that predisposes individuals to seizures, as well as cognitive and emotional dysfunctions. Different studies have demonstrated that inflammation contributes to the pathophysiology of epilepsy. Indeed, seizures change the peripheral inflammatory pattern, which, in turn, could contribute to seizures. However, the cause of the altered production of peripheral inflammatory mediators is not known. The PI3K/mTOR/GSK3β pathway is important for different physiological and pharmacological phenomena. Therefore, in the present study, we tested the hypothesis that the PI3K/mTOR/GSK3β pathway is deregulated in immune cells from patients with epilepsy and contributes to the abnormal production of inflammatory mediators.

Methods: Patients with temporal lobe epilepsy presenting hippocampal sclerosis and controls aged between 18 and 65 years-old were selected for this study. Peripheral blood was collected for the isolation of peripheral mononuclear blood cells (PBMC). Cells were pre-incubated with different PI3K, mTOR and GSK-3 inhibitors for 30 min and further stimulated with phytohaemaglutinin (PHA) or vehicle for 24 h. The supernatant was used to evaluate the production of IL-1β, IL-6, IL-10, TNF e IL-12p70.

Results: Non-selective inhibition of PI3K, as well as inhibition of PI3Kγ and GSK-3, reduced the levels of TNF and IL-10 in PHA-stimulated cells from TLE individuals. This stimulus increased the production of IL-12p70 only in cells from TLE individuals, while the inhibition of PI3K and mTOR enhanced the production of this cytokine. On the other hand, inhibition of GSK3 reduced the PHA-induced production of IL-12p70.

Conclusions: Herein we demonstrated that the production of cytokines by immune cells from patients with TLE differs from non-epileptic patients. This differential regulation may be associated with the altered activity and responsiveness of intracellular molecules, such as PI3K, mTOR and GSK-3, which, in turn, might contribute to the inflammatory state that exists in epilepsy and its pathogenesis.
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http://dx.doi.org/10.1016/j.neulet.2021.135948DOI Listing
June 2021

Acute exercise increases BDNF serum levels in patients with Parkinson's disease regardless of depression or fatigue.

Eur J Sport Sci 2021 May 4:1-21. Epub 2021 May 4.

PhD, Laboratory of Neurobiology, Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil. - 0000-0003-1383-8550.

Studies have consistently reported a decreased level of brain derived neurotrophic factor (BDNF) in individuals with Parkinson's disease (PD). The benefits of exercise on BDNF levels are well-documented in humans, however, the effects of acute exercise are inconclusive in neurological disorders. In addition, there are no studies investigating a precursor molecule - proBDNF - and its comparison to patients with vs. without depression or fatigue. Thirty patients with PD were instructed to walk on a treadmill at light to moderate intensity for 30 minutes. Generalized Estimating Equation (GEE) showed mature BDNF (mBDNF) The present study showed that a single bout of light to moderate-intensity exercise increases mBDNF serum levels in patients with PD regardless of depression and fatigue. Our finding is important because it is necessary investigate methods to enhance the gains made by rehabilitation, especially when considering a short period of rehabilitation in different health services. The increase in mBDNF level can lead to an enhancement of neuroplasticity and facilitate the improvement of motor performance. No effect on proBDNF level could be explained, as this precursor molecule is cleaved by intracellular or extracellular enzymes.
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http://dx.doi.org/10.1080/17461391.2021.1922505DOI Listing
May 2021

Circulating Angiotensin-(1-7) Is Reduced in Alzheimer's Disease Patients and Correlates With White Matter Abnormalities: Results From a Pilot Study.

Front Neurosci 2021 6;15:636754. Epub 2021 Apr 6.

Laboratório Interdisciplinar de Investigação Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil.

Introduction: Alzheimer's disease (AD) is the leading cause of dementia worldwide. Despite the extensive research, its pathophysiology remains largely unelucidated. Currently, more attention is being given to the disease's vascular and inflammatory aspects. In this context, the renin-angiotensin system (RAS) emerges as a credible player in AD pathogenesis. The RAS has multiple physiological functions, conducted by its two opposing axes: the classical, led by Angiotensin II (Ang II), and the alternative, driven by Angiotensin-(1-7) [Ang-(1-7)]. These peptides were shown to interact with AD pathology in animal studies, but evidence from humans is scarce. Only 20 studies dosed RAS molecules in AD patients' bloodstream, none of which assessed both axes simultaneously. Therefore, we conducted a cross-sectional, case-control exploratory study to compare plasma levels of Ang II and Ang-(1-7) in AD patients vs. age-matched controls. Within each group, we searched for correlations between RAS biomarkers and measures from magnetic resonance imaging (MRI).

Methods: We evaluated patients with AD (n = 14) and aged-matched controls (n = 14). Plasma Ang II and Ang-(1-7) were dosed using ELISA. Brain MRI was performed in a 3 Tesla scan, and a three-dimensional T1-weighted volumetric sequence was obtained. Images were then processed by FreeSurfer to calculate: (1) white matter hypointensities (WMH) volume; (2) volumes of hippocampus, medial temporal cortex, and precuneus. Statistical analyses used non-parametrical tests (Mann-Whitney and Spearman).

Results: Ang-(1-7) levels in plasma were significantly lower in the AD patients than in controls [median (25th-75th percentiles)]: AD [101.5 (62.43-126.4)] vs. controls [209.3 (72-419.1)], = 0.014. There was no significant difference in circulating Ang II. In the AD patients, but not in controls, there was a positive and significant correlation between Ang-(1-7) values and WMH volumes (Spearman's rho = 0.56, = 0.038). Ang-(1-7) did not correlate with cortical volumes in AD or in controls. Ang II did not correlate with any MRI variable in none of the groups.

Conclusion: If confirmed, our results strengthen the hypothesis that RAS alternative axis is downregulated in AD, and points to a possible interaction between Ang-(1-7) and cerebrovascular lesions in AD.
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http://dx.doi.org/10.3389/fnins.2021.636754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063113PMC
April 2021

Peri-Ictal and Para-Ictal Psychiatric Phenomena: A Relatively Common Yet Unrecognized Disorder.

Curr Top Behav Neurosci 2021 Mar 17. Epub 2021 Mar 17.

Instituto de Ensino e Pesquisa, Santa Casa BH, Belo Horizonte, Brazil.

Patients with epilepsy can experience different neuropsychiatric symptoms related (peri-ictal) or not (interictal) with seizures. Peri-ictal symptoms can precede (pre-ictal) or follow (post-ictal) the seizure, or even be the expression of the seizure activity (ictal). Neuropsychiatric symptoms, such as irritability and apathy, are among the most frequent pre-ictal manifestations. Ictal fear is reported by around 10% of patients with focal seizures, and sometimes can be difficult to differentiate from panic attacks. Post-ictal anxiety, mood and psychotic symptoms are also frequently reported by patients. Peri-ictal phenomena can occur as isolated symptom or as a cluster of symptoms, sometimes resembling a full-blown psychiatric syndrome. Actually, peri-ictal and interictal neuropsychiatric manifestations seem to be closely associated.
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http://dx.doi.org/10.1007/7854_2021_223DOI Listing
March 2021

Serotonin and dopamine receptors profile on peripheral immune cells from patients with temporal lobe epilepsy.

J Neuroimmunol 2021 05 5;354:577534. Epub 2021 Mar 5.

Laboratório de Neurofarmacologia, Departamento de Farmacologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil; Programa de Neurociências, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil. Electronic address:

The role of inflammation and immune cells has been demonstrated in neurological diseases, including epilepsy. Leukocytes, as well as inflammatory mediators, contribute to abnormal processes that lead to a reduction in seizure threshold and synaptic reorganization. In this sense, identifying different phenotypes of circulating immune cells is essential to understanding the role of these cells in epilepsy. Immune cells can express a variety of surface markers, including neurotransmitter receptors, such as serotonin and dopamine. Alteration in these receptors expression patterns may affect the level of inflammatory mediators and the pathophysiology of epilepsy. Therefore, in the current study, we evaluated the expression of dopamine and serotonin receptors on white blood cells from patients with temporal lobe epilepsy with hippocampal sclerosis (TLE-HS). Blood samples from 17 patients with TLE-HS and 21 controls were collected. PBMC were isolated and stained ex vivo for flow cytometry. We evaluated the expression of serotonin (5-HT, 5-HT, 5-HT, 5-HT, 5-HT, 5-HT, 5-HT), and dopamine receptors (D, D, D, D, and D) on the cell surface of lymphocytes and innate immune cells (monocytes and granulocytes). Our results demonstrated that innate cells and lymphocytes from patients with TLE-HS showed high mean fluorescent intensity (MFI) for 5-HT, 5-HT, 5-HT and 5-HT compared to controls. No difference was observed for 5-HT. For dopamine receptors, the expression of D, D, D and D receptors was higher on innate cells from patients with TLE-HS when compared to controls for the MFI. Regarding lymphocytes population, D expression was increased in patients with TLE-HS. In conclusion, there are alterations in the expression of serotonin and dopamine receptors on immune blood cells of patients with TLE-HS. Although the biological significance of these findings still needs to be further investigated, these changes may contribute to the understanding of TLE-HS pathophysiology.
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http://dx.doi.org/10.1016/j.jneuroim.2021.577534DOI Listing
May 2021

Tumor necrosis factor superfamily molecules are increased in behavioral variant frontotemporal dementia and correlate with cortical atrophy: An exploratory investigation.

J Neuroimmunol 2021 05 27;354:577531. Epub 2021 Feb 27.

Laboratório Interdisciplinar de Investigação Médica, Faculdade de Medicina, UFMG, Belo Horizonte, MG, Brazil; Departamento de Clínica Médica, Faculdade de Medicina, UFMG, Belo Horizonte, MG, Brazil; Programa de Pós-Graduação em Neurociências, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil. Electronic address:

Frontotemporal dementia (FTD) is the second most frequent cause of young-onset dementia. Even though immune-mediated and neuroinflammatory factors have been recognized as potential pathophysiological mechanisms, the role of specific immune molecules, such as the tumor necrosis factor (TNF) superfamily, remains elusive. The aim of this study was to investigate TNF Superfamily Molecules (TNF, TNF-related weak inducer of apoptosis [TWEAK], soluble TNF receptor type 1 [sTNFRI] and soluble TNF receptor type 2 [sTNFRII]) in patients with behavioral variant FTD (bvFTD) and controls, and to explore potential associations with clinical parameters and brain atrophy. This study included two groups of participants matched for age, sex and schooling years: patients with probable bvFTD (n = 17, mean age = 64.9 years, 6 women/11 men) and healthy controls (HC, n = 17; mean age = 63.9 years, 10 women/7 men). All participants underwent comprehensive cognitive assessment and structural brain imaging with 3 T magnetic resonance imaging. Plasma levels of TNF, TWEAK, sTNFRI and sTNFRII were determined by ELISA. We conducted voxel-based morphometry analyses to investigate correlations between grey matter (GM) atrophy and plasma levels of TNF, TWEAK, sTNFRI and sTNFRII within bvFTD group. Compared to HC, bvFTD patients had lower cognitive scores and marked frontotemporal atrophy. Patients with bvFTD had significantly higher plasma levels of TNF (p < 0.0001), sTNFRI (p < 0.001), and sTNFRII (p < 0.0001), and similar levels of TWEAK in comparison with controls. The levels of sTNFRII were positively correlated with GM atrophy involving temporal poles, precuneus and cerebellum in bvFTD patients, while the levels of TWEAK positively correlated with right superior temporal gyrus. Our results implicate TNF superfamily in the pathophysiology of FTD.
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http://dx.doi.org/10.1016/j.jneuroim.2021.577531DOI Listing
May 2021

Investigating potential associations between neurocognition/social cognition and oxidative stress in schizophrenia.

Psychiatry Res 2021 Apr 23;298:113832. Epub 2021 Feb 23.

Neuroscience Program, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil; Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil.

Introduction: Deficits in neurocognition and social cognition play a critical role in the functional impairment of patients with schizophrenia. Increased oxidative stress has been evidenced in schizophrenia. Increased oxidative stress can affect neuronal function and lead to impairments in neurocognitive functions (especially working memory) and social cognition.

Objective: To investigate deficits in neurocognition and social cognition and their potential association with oxidative stress biomarkers in schizophrenia.

Material And Methods: Eight-five clinically stable patients with schizophrenia and 75 controls were enrolled in this study. Neurocognition was evaluated through the Brief Assessment of Cognition in Schizophrenia (BACS). Social cognition was assessed through the Hinting Task - a test of theory of mind - and an emotion processing test, Facial Emotion Recognition Test (FERT-100). Oxidative stress was assessed by measuring serum levels of glutathione (GSH) and thiobarbituric acid reactive substances (TBARS).

Results: Patients had decreased serum levels of GSH (Z=3.56; p<0.001) and increased TBARS (Z=5.51; P<0.001) when compared with controls. TBARS levels are higher in patients using first generation antipsychotics. Higher serum levels of TBARS in patients were associated with poor performance in working memory test (r=-0.39; p=0.002), even when controlling for age and negative symptoms (Standard Beta: -0.36; CI= -2.52 a -13.71).

Discussion: The association between greater lipid peroxidation, as assessed by TBARS, and worse performance in working memory corroborates theoretical models of greater vulnerability of schizophrenia to oxidative stress.
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http://dx.doi.org/10.1016/j.psychres.2021.113832DOI Listing
April 2021

Dementia in Latin America: Paving the way toward a regional action plan.

Alzheimers Dement 2021 02 20;17(2):295-313. Epub 2020 Nov 20.

Hospital Geral de Fortaleza, University of Fortaleza, Brazil.

Across Latin American and Caribbean countries (LACs), the fight against dementia faces pressing challenges, such as heterogeneity, diversity, political instability, and socioeconomic disparities. These can be addressed more effectively in a collaborative setting that fosters open exchange of knowledge. In this work, the Latin American and Caribbean Consortium on Dementia (LAC-CD) proposes an agenda for integration to deliver a Knowledge to Action Framework (KtAF). First, we summarize evidence-based strategies (epidemiology, genetics, biomarkers, clinical trials, nonpharmacological interventions, networking, and translational research) and align them to current global strategies to translate regional knowledge into transformative actions. Then we characterize key sources of complexity (genetic isolates, admixture in populations, environmental factors, and barriers to effective interventions), map them to the above challenges, and provide the basic mosaics of knowledge toward a KtAF. Finally, we describe strategies supporting the knowledge creation stage that underpins the translational impact of KtAF.
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http://dx.doi.org/10.1002/alz.12202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984223PMC
February 2021

The link between nutrition and Alzheimer's disease: from prevention to treatment.

Neurodegener Dis Manag 2021 04 8;11(2):155-166. Epub 2021 Feb 8.

Department of Psychiatry & Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77054, USA.

Alzheimer's disease (AD) is the most common cause of dementia. To date, there is no effective pharmacological strategy to slow or stop disease progression. In this context, multiple alternative therapeutic strategies have been investigated for AD. This review addresses the potential role of nutrition interventions in AD prevention and treatment. Nutritional strategies for AD have been based on four pillars: maintaining a healthy weight (i.e., prevention and/or treatment of obesity, especially in midlife and prevention of weight loss in the later stages of AD); correction of nutritional deficiencies; adequate consumption of micronutrients (vitamins and minerals), especially those implicated in the pathways of AD pathophysiology; and microbiota modulation.
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http://dx.doi.org/10.2217/nmt-2020-0023DOI Listing
April 2021

Different patterns of gray matter atrophy in behavioral variant frontotemporal dementia with and without episodic memory impairment.

Int J Geriatr Psychiatry 2021 02 1. Epub 2021 Feb 1.

Grupo de Neurologia Cognitiva e do Comportamento, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

Background: Differentiating patients with behavioral variant frontotemporal dementia (bvFTD) from Alzheimer's disease (AD) is important as these two conditions have distinct treatment and prognosis. Using episodic impairment and medial temporal lobe atrophy as a tool to make this distinction has been debatable in the recent literature, as some patients with bvFTD can also have episodic memory impairment and medial temporal lobe atrophy early in the disease.

Objectives: To compare brain atrophy patterns of patients with bvFTD with and without episodic memory impairment to that of patients with AD.

Methods: We analyzed 19 patients with bvFTD, 21 with AD and 21 controls, matched by age, sex, and years of education. They underwent brain MRI and the memory test from the Brief Cognitive Battery (BCB) to assess episodic memory. We then categorized the bvFTD group into amnestic (BCB delayed recall score <7) and non-amnestic.

Results: The amnestic bvFTD group (n = 8) had significant gray matter atrophy in the left parahippocampal gyrus, right cingulate and precuneus regions compared with the nonamnestic group. Compared with AD, amnestic bvFTD had more atrophy in the left fusiform cortex, left insula, left inferior temporal gyrus and right temporal pole, whereas patients with AD had more atrophy in the left hippocampus, left frontal pole and left angular gyrus.

Conclusions: There is a group of amnestic bvFTD patients with episodic memory dysfunction and significant atrophy in medial temporal structures, which poses a challenge in considering only these features when differentiating bvFTD from AD clinically.
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http://dx.doi.org/10.1002/gps.5503DOI Listing
February 2021

Aerobic Training Modulates the Increase in Plasma Concentrations of Cytokines in response to a Session of Exercise.

J Environ Public Health 2021 16;2021:1304139. Epub 2021 Jan 16.

Laboratório de Imunofarmacologia, Departamento de Bioquímica e Imunologia (ICB/UFMG), Belo Horizonte, Brazil.

Acute physical exercise can modulate immune function. For example, acute exercise is known to increase the circulating concentration of cytokines. Exercise is also known to modulate immune function chronically. It is not known whether exercise training can result in training of the immune system. Here, we investigated the effects of six weeks of aerobic training on cytokine responses induced by acute exercise until fatigue. Twelve healthy men performed a fatiguing exercise at the anaerobic threshold (AT) intensity. After the training period, the participants performed another bout of acute exercise at the same duration and intensity of the pretraining situation. The analysis was made at the beginning, end, and at 10, 30, and 60 minutes during the recovery period. Training at AT induced a gain of 11.2% of exercise capacity. Before training, a single bout of acute exercise induced a significant increase in plasma levels of cytokines, including IL-6, TNF-, sTNFR1, IL-10, CXCL10, BDNF, leptin, resistin, and adiponectin. After six weeks of aerobic training, levels of IL-6, sTNFR1, BDNF, and leptin increased to a lesser extent after an acute bout exercise at the same absolute intensity as the pretraining period. Responses to the same relative exercise intensity were similar to those observed before exercise. These results show that aerobic training is associated with training of acute immune responses to acute exercise until fatigue.
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http://dx.doi.org/10.1155/2021/1304139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826215PMC
January 2021

Acute effects of dry extract of ginger on energy expenditure in eutrophic women: A randomized clinical trial.

Clin Nutr ESPEN 2021 Feb 9;41:168-174. Epub 2020 Nov 9.

Department of Nutrition, Nursing School, Universidade Federal de Minas Gerais (UFMG), Av. Alfredo Balena, 190 Santa Efigênia CEP 30130100, Belo Horizonte, Minas Gerais, Brazil. Electronic address:

Background & Aims: The thermic effect of food (TEF) is one of the components of total energy expenditure (TEE). Some bioactive compounds present in food could be useful to increase TEE. In this context, ginger has been extensively used as a thermogenic food despite no clear effect has been demonstrated yet. Herein, we evaluated the acute thermogenic effect of gingerol, a bioactive compound present in ginger, in healthy women.

Methods: We carried out a randomized double-masked, cross-over and placebo-controlled clinical trial with 20 healthy eutrophic women. Anthropometric, body composition, indirect calorimetry and clinical variables were collected at baseline and throughout the intervention phase. A standardized breakfast was offered together with two dry extract of ginger capsules (5% gingerol) or a placebo (cellulose). Indirect calorimetry, blood pressure, heart rate, axillary temperature and blood collection were assessed at baseline and thereafter, at 30, 60, 120, 180 and 240 min postprandial. The analyses were repeated with a minimum of seven days' washout period.

Results: Ginger intake did not increase the TEF of a standardized breakfast compared to the placebo. Oxygen consumption, respiratory quotient, blood pressure, heart rate, axillary temperature and metabolic profile were not different as well.

Conclusions: Our data show that gingerol did not modify the acute TEF in healthy women. More studies in human subjects, using different concentrations of gingerol, administration methods and intervention type (chronic effect) are necessary to clarify the putative thermogenic effect of ginger. Registered at ClinicalTrials.gov (Thermogenic Effect of Ginger - NCT03089593).
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http://dx.doi.org/10.1016/j.clnesp.2020.10.001DOI Listing
February 2021

Diabetes and impaired fasting glucose in a population-based sample of individuals aged 75 + years: associations with cognition, major depressive disorder, functionality and quality of life-the Pietà study.

Neurol Sci 2021 Jan 13. Epub 2021 Jan 13.

Programa de Pós-graduação em Ciências Aplicadas à Saúde do Adulto, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.

Objectives: To investigate the rates of diabetes mellitus (DM) and impaired fasting glucose (IFG) in a population-based sample of individuals aged 75 + years old and their associations with cognitive performance, depression, functionality, and quality of life (QoL).

Study Design: Overall, 350 people participated in the study. Assessments of cognition, mood, functionality and QoL were performed using the mini-mental state examination (MMSE), clock-drawing, category fluency tests, the Mini-International Neuropsychiatric Interview, Pfeffer's Functional Activities Questionnaire, and the WHO Quality of Life-Old (WHOQOL-OLD).

Results: IFG (ADA criteria) was identified in 42.1% of the sample, while the DM rate was 24.1%. Lack of knowledge of the DM diagnosis and lack of treatment occurred in 27% and 39% of the sample, respectively. Rates of dementia and depression, MMSE, category fluency scores, and previous cardiovascular events did not differ between the glycaemic groups. Individuals with DM performed worse on the clock-drawing test, functionality, and WHOQOL-OLD than the other participants. Individuals with IFG presented similar QoL and functionality when compared with the group without DM.

Conclusions: IFG and DM were common in this population-based sample aged 75 + years old, as were inadequate diagnoses and treatments of DM. DM individuals presented poor performance in the executive function test, functionality, and QoL. Further studies are recommended to investigate the value of an IFG diagnosis among the most elderly population.
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http://dx.doi.org/10.1007/s10072-020-05008-xDOI Listing
January 2021

Incidence and predictors of stroke in patients with rheumatic heart disease.

Heart 2021 May 7;107(9):748-754. Epub 2021 Jan 7.

Post Graduation Program in Infectious Diseases and Tropical Medicine, School of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

Objective: Ischaemic stroke is a severe complication of rheumatic heart disease (RHD), which may result in permanent disability and death. This study aimed to assess the incidence and predictors of stroke in patients with RHD in the current era of evidence-based recommendations for prevention.

Methods: Consecutive patients with RHD diagnosed by clinical and echocardiographic criteria were selected. A structured clinical and neurological assessment was performed to determine the aetiology and classification of stroke at enrolment. The primary endpoint was an ischaemic cerebrovascular event, which included fatal or non-fatal stroke. Risk of stroke was estimated accounting for competing risks.

Results: A total of 515 patients were enrolled, 438 women (85%), 46±12 years of age. The most frequent valve lesion was mixed mitral (80%). At the time of enrolment, 92 patients (18%) had a prior stroke, with anterior circulation infarction being the most frequent topography (72%). During the mean follow-up of 3.9 years, 27 patients (5.2%) had stroke with the overall incidence of 1.47 strokes per 100 patient-years. Predictors of stroke by the Cox model were prior stroke (adjusted HR 5.395, 95% CI 2.272 to 12.811), age (HR 1.591, 95% CI 1.116 to 2.269) and atrial fibrillation (AF) at baseline (HR 2.945, 95% CI 1.083 to 8.007). By considering death as a competing risk, the effect of AF on stroke risk was attenuated (HR 2.287, 95% CI 0.962 to 5.441).

Conclusions: In this large cohort of patients with RHD, stroke occurred in 5.2% of the patients, which was predicted by age, AF and prior stroke. The effect of AF on stroke risk estimation was influenced by death as competing risk.
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http://dx.doi.org/10.1136/heartjnl-2020-318054DOI Listing
May 2021

NLRP3 and NLRP1 inflammasomes are up-regulated in patients with mesial temporal lobe epilepsy and may contribute to overexpression of caspase-1 and IL-β in sclerotic hippocampi.

Brain Res 2021 Feb 29;1752:147230. Epub 2020 Dec 29.

Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, TX, United States.

Inflammation plays a role in the pathophysiology of mesial temporal lobe epilepsy (MTLE). Inflammasome pathways, including the NLRP1 and NLRP3-induced ones, promote neuroinflammation and pyroptosis through interleukin (IL)-1β and caspase-1 action. Evaluation of NLRP1 in sclerotic hippocampi is scarce and there are no data on NLRP3 in human TLE. The aim of this study was to evaluate the expression of these proteins alongside caspase-1 and IL-1β in the hippocampi of patients with TLE compared to control samples. We also sought to investigate peripheral levels of caspase-1 and IL-1β in an independent cohort. Sclerotic and control hippocampi were collected for both histological and immunohistochemical analyses of NLRP1, NLRP3, caspase-1 and IL-1β; plasma was sampled for the measurement of caspase-1 and IL-1β levels through enzyme-linked immunoassay (ELISA) and cytometric bead array (CBA). Sclerotic hippocampi displayed higher expression of the measured proteins than control. Both glia and neurons showed activation of these pathways. Additionally, increased expression of NLRP1 and NLRP3 was associated with elevated plasma levels of IL-1β and in TLE, and increased levels of peripheral caspase-1 were associated with bilateral hippocampal sclerosis (HS). In conclusion, NLRP1 and NLRP3 are up-regulated in sclerotic hippocampi, what may be responsible, at least in part, for the increased hippocampal expression of caspase-1 and IL-1β. Our data suggest a role for inflammasome activation in central and peripheral inflammation in TLE.
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http://dx.doi.org/10.1016/j.brainres.2020.147230DOI Listing
February 2021

The impact of SARS-CoV-2 in dementia across Latin America: A call for an urgent regional plan and coordinated response.

Alzheimers Dement (N Y) 2020 23;6(1):e12092. Epub 2020 Nov 23.

Global Brain Health Institute (GBHI) University of California San Francisco (UCSF) San Francisco California USA.

The SARS-CoV-2 global pandemic will disproportionately impact countries with weak economies and vulnerable populations including people with dementia. Latin American and Caribbean countries (LACs) are burdened with unstable economic development, fragile health systems, massive economic disparities, and a high prevalence of dementia. Here, we underscore the selective impact of SARS-CoV-2 on dementia among LACs, the specific strain on health systems devoted to dementia, and the subsequent effect of increasing inequalities among those with dementia in the region. Implementation of best practices for mitigation and containment faces particularly steep challenges in LACs. Based upon our consideration of these issues, we urgently call for a coordinated action plan, including the development of inexpensive mass testing and multilevel regional coordination for dementia care and related actions. Brain health diplomacy should lead to a shared and escalated response across the region, coordinating leadership, and triangulation between governments and international multilateral networks.
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http://dx.doi.org/10.1002/trc2.12092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683959PMC
November 2020

Brain-derived neurotrophic factor is down regulated after bovine alpha-herpesvirus 5 infection in both wild-type and TLR3/7/9 deficient mice.

J Vet Med Sci 2021 Feb 7;83(2):180-186. Epub 2020 Dec 7.

Laboratory of Cellular and Molecular Pathology, Department of General Pathology, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, 31270-901, Brazil.

Neurotrophic factors have been implicated in the control of neuronal survival and plasticity in different brain diseases. Meningoencephalitis caused by bovine alpha-herpesvirus 5 (BoHV-5) infection is a frequent neurological disease of young cattle, being the involvement of apoptosis in the development of neuropathological changes frequently discussed in the literature. It's well known that Toll-like receptors (TLRs) can activate neuroinflammatory response and consequently lead to neuronal loss. However, there are no studies evaluating the expression of neurotrophic factors and their association with brain pathology and TLRs during the infection by BoHV-5. The current study aimed to analyze brain levels of neurotrophic factors along with neuropathological changes during acute infection by BoHV-5 in wild-type (WT) and TLR3/7/9 (TLR3/7/9) deficiency mice. The infection was induced by intracranial inoculation of 1 × 10 TCID of BoHV-5. Infected animals presented similar degrees of clinical signs and neuropathological changes. Both infected groups had meningoencephalitis and neuronal damage in CA regions from hippocampus. BoHV-5 infection promoted the proliferation of Iba-1 positive cells throughout the neuropil, mainly located in the frontal cortex. Moreover, significant lower levels of brain-derived neurotrophic factor (BDNF) were detected in both BoHV-5 infected WT and TLR3/7/9 deficient mice, compared with non-infected animals. Our study showed that BDNF down regulation was associated with brain inflammation, reactive microgliosis and neuronal loss after bovine alpha-herpesvirus 5 infection in mice. Moreover, we demonstrated that combined TLR3/7/9 deficiency does not alter those parameters.
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http://dx.doi.org/10.1292/jvms.20-0204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972877PMC
February 2021

Gene Expression Profiling in Huntington's Disease: Does Comorbidity with Depressive Symptoms Matter?

Int J Mol Sci 2020 Nov 11;21(22). Epub 2020 Nov 11.

Neuropsychiatry Program, Louis A Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77054, USA.

Huntington's disease (HD) is an inherited neurodegenerative disease. Besides the well-characterized motor symptoms, HD is marked by cognitive impairment and behavioral changes. In this study, we analyzed the blood of HD gene carries using RNA-sequencing techniques. We evaluated samples from HD gene carriers with ( = 8) and without clinically meaningful depressive symptoms ( = 8) compared with healthy controls ( = 8). Groups were age- and sex-matched. Preprocessing of data and between-group comparisons were calculated using DESeq2. The Wald test was used to generate -values and log2 fold changes. We found 60 genes differently expressed in HD and healthy controls, of which 21 were upregulated and 39 downregulated. Within HD group, nineteen genes were differently expressed between patients with and without depression, being 6 upregulated and 13 downregulated. Several of the top differentially expressed genes are involved in nervous system development. Although preliminary, our findings corroborate the emerging view that in addition to neurodegenerative mechanisms, HD has a neurodevelopmental component. Importantly, the emergence of depression in HD might be related to these mechanisms.
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http://dx.doi.org/10.3390/ijms21228474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697115PMC
November 2020

Is neurotrophin-3 (NT-3): a potential therapeutic target for depression and anxiety?

Expert Opin Ther Targets 2020 12 26;24(12):1225-1238. Epub 2020 Nov 26.

Neuropsychiatry Program, Department of Psychiatry & Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston , Houston, TX, Brazil.

: Neurotrophin-3 (NT-3) is thought to play a role in the neurobiological processes implicated in mood and anxiety disorders. NT-3 is a potential pharmacological target for mood disorders because of its effects on monoamine neurotransmitters, regulation of synaptic plasticity and neurogenesis, brain-derived neurotrophic factor (BDNF) signaling boosting, and modulation of the hypothalamic-pituitary-adrenal (HPA) axis. The mechanisms underlying NT-3 anxiolytic properties are less clear and require further exploration and definition. : The evidence that supports NT-3 as a pharmacological target for anxiety and mood disorders is presented and this is followed by a reflection on the quandaries, stumbling blocks, and future perspectives for this novel target. : There is evidence for miRNAs being key post-transcriptional regulators of neurotrophin-3 receptor gene (NTRK3) in anxiety disorders; however, the anxiolytic properties of NT-3 need further examination and delineation. Moreover, NT-3 expression by non-neuronal cells and its role in brain circuits that participate in anxiety and mood disorders require further scrutiny. Further work is vital before progression into clinical trials can be realized.
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http://dx.doi.org/10.1080/14728222.2020.1846720DOI Listing
December 2020

Social Cognition Tests Can Discriminate Behavioral Variant Frontotemporal Dementia From Alzheimer's Disease Independently of Executive Functioning.

Arch Clin Neuropsychol 2020 Oct 9. Epub 2020 Oct 9.

Laboratório Interdisciplinar de Investigação Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.

Objective: To investigate the accuracy of the Social and Emotional Assessment-short version (Mini-SEA) to differentiate subgroups of behavioral variant of frontotemporal dementia (bvFTD) and Alzheimer's disease (AD) defined according to executive performance.

Methods: bvFTD (n = 21), AD (n = 20), and healthy controls (HC, n = 23) underwent the Mini-SEA, comprising the Facial Emotion Recognition Test (FERT) and the faux-pas test. AD and bvFTD patients were classified according to their performance in the Frontal Assessment Battery into dysexecutive and nondysexecutive subgroups.

Results: The area under the curve (AUC) values for the faux-pas test were 0.87 (dysexecutive-bvFTD vs. dysexecutive-AD) and 0.96 (non-dysexecutive-bvFTD vs. nondysexecutive-AD). The AUC values for FERT were 0.99 (dysexecutive-bvFTD vs. dysexecutive-AD) and 0.65 (nondysexecutive-bvFTD vs. nondysexecutive-AD); the AUC values for the Mini-SEA (total-score) were 0.95 (dysexecutive-bvFTD vs. dysexecutive-AD) and 0.88 (nondysexecutive-bvFTD vs. nondysexecutive-AD).

Discussion: Social Cognition tests accurately distinguish bvFTD from AD regardless of the executive profile.
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http://dx.doi.org/10.1093/arclin/acaa084DOI Listing
October 2020

Effects of tDCS on neuroplasticity and inflammatory biomarkers in bipolar depression: Results from a sham-controlled study.

Prog Neuropsychopharmacol Biol Psychiatry 2021 Mar 4;105:110119. Epub 2020 Oct 4.

Laboratory of Neurosciences (LIM-27), Instituto Nacional de Biomarcadores em Neuropsiquiatria (INBioN), Department and Institute of Psychiatry, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; Department of Internal Medicine, Faculdade de Medicina da Universidade de São Paulo & Hospital Universitário, Universidade de São Paulo, Av. Prof Lineu Prestes 2565, 05508-000 São Paulo, Brazil. Electronic address:

Objectives: We investigated the role of peripheral biomarkers associated with neuroplasticity and immune-inflammatory processes on the effects of transcranial direct current stimulation (tDCS), a safe, affordable, and portable non-invasive neuromodulatory treatment, in bipolar depression.

Methods: This is an exploratory analysis using a dataset from the sham-controlled study the Bipolar Depression Electrical Treatment Trial (BETTER)(clinicaltrials.govNCT02152878). Participants were 52 adults with type I or II bipolar disorder in a moderate-to-severe depressive episode, randomized to 12 bifrontal active or sham tDCS sessions over a 6-week treatment course. Plasma levels of brain derived neurotrophic factor (BDNF), glial cell derived neurotrophic factor (GDNF), interleukins (IL) 2, 4, 6, 8, 10, 18, 33, 1β, 12p70, 17a, interferon gamma (IFN), tumor necrosis factor alpha (TNF) and its soluble receptors 1 and 2, ST2, and KLOTHO were investigated at baseline and endpoint. We performed analyses unadjusted for multiple testing to evaluate whether baseline biomarkers were predictive for depression improvement and changed during treatment using linear regression models.

Results: A time x group interaction (Cohen's d: -1.16, 95% CI = -1.96 to -0.3, p = .005) was found for IL-8, with greater reductions after active tDCS. Higher baseline IL-6 plasma levels was associated with symptomatic improvement after tDCS (F = 5.43; p = .025). Other associations were not significant.

Conclusions: Our exploratory findings suggested that IL-6 is a potential predictor of tDCS response and IL-8 might decrease after tDCS; although confirmatory studies are warranted due to the multiplicity of comparisons.
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http://dx.doi.org/10.1016/j.pnpbp.2020.110119DOI Listing
March 2021

Inside minds, beneath diseases: social cognition in amyotrophic lateral sclerosis-frontotemporal spectrum disorder.

J Neurol Neurosurg Psychiatry 2020 12 22;91(12):1279-1282. Epub 2020 Sep 22.

Programa de Pós-Graduação em Neurociências, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

Objective: To compare social cognition performance between patients with amyotrophic lateral sclerosis (ALS) and those patients with behavioural variant frontotemporal dementia (bvFTD).

Methods: We included 21 participants with ALS, 20 with bvFTD and 21 healthy controls who underwent a comprehensive cognitive battery, including the short version of the Social Cognition and Emotional Assessment (Mini-SEA), which comprises the test and Facial Emotion Recognition Test (FERT); Mini-Mental State Examination; Frontal Assessment Battery; lexical fluency (F-A-S), category fluency (animals/minute), digit span (direct and backwards) tests and the Hayling test. A post hoc analysis was conducted with the patients with ALS divided into two subgroups: patients without cognitive impairment (ALScn; n=13) and patients with cognitive impairment (ALSci; n=8).

Results: No significant difference was noted between participant groups in terms of the age, sex and education. ALS-total group and patients with bvFTD had similar disease durations. Patients with ALSci performed poorly when compared with controls with regard to the FERT (p<0.001), the (p<0.004) and the Mini-SEA (p<0.002) total scores. Moreover, patients with bvFTD performed poorly in comparison with controls in executive and social cognition tests. The performance of patients with ALSci was similar to that of patients with bvFTD, while the performance of patients with ALScn was similar to that of controls.

Discussion: Our findings support a cognitive continuum between ALS and bvFTD and shed light on the cognitive heterogeneity of ALS, expanding its possible neuropsychological profiles.
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http://dx.doi.org/10.1136/jnnp-2020-324302DOI Listing
December 2020

Stress, anxiety, self-efficacy, and the meanings that physical therapy students attribute to their experience with an objective structured clinical examination.

BMC Med Educ 2020 Sep 10;20(1):296. Epub 2020 Sep 10.

Department of Physical Therapy, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.

Background: Excessive stress and anxiety can impair learning. The objective structured clinical examination (OSCE) is a valuable tool to assess and promote the acquisition of clinical skills. However, significant OSCE-related stress and anxiety are frequently reported. The aim of this study was to investigate the relationships between physiological stress, self-reported levels of anxiety due to an OSCE, self-efficacy, and the meanings that physical therapy students attribute to their experience with the exam.

Design: Concurrent mixed methods study.

Methods: A total of 32 students took part in this study. All were enrolled in the third semester of a 10-semester Physical Therapy Bachelor Program. Salivary cortisol levels, self-reported anxiety (State-Trait Anxiety Inventory, STAI) were measured before the OSCE. Exam scores and self-efficacy ratings were also recorded. Correlations between variables were tested with the Pearson correlation, with ɑ at 0.05. Semi-structured interviews were used to explore the personal perspectives of students. Thematic analysis was used to investigate emergent themes.

Results: Trait anxiety scores were significantly higher than normative values (p < 0.001). A high proportion of students showed high (STAI> 49) state anxiety (37.5%) and trait anxiety (65.6%). Salivary cortisol was not associated anxiety (p > 0.05). Neither stress nor anxiety correlated with OSCE scores. A moderate and significant direct correlation was found for self-efficacy scores and OSCE scores (r = 0.475, p = 0.007). Students reported that confidence had a calming effect and led to better self-perceived performance. They also reported that the OSCE can provide meaningful learning experiences despite being stressful.

Conclusions: A high proportion of our students reported a stable/lingering negative affect. However, neither stress nor anxiety related to OSCE scores. Students' confidence in their capabilities was correlated with their performance. Their subjective reports suggest that self-confidence may have protected them from the negative effects of stress and anxiety on academic performance.
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http://dx.doi.org/10.1186/s12909-020-02202-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488334PMC
September 2020

Inflammation in Huntington's disease: A few new twists on an old tale.

J Neuroimmunol 2020 11 31;348:577380. Epub 2020 Aug 31.

Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Laboratório Interdisciplinar de Investigação Médica, Faculdade de Medicina, UFMG, Belo Horizonte, Minas Gerais, Brazil. Electronic address:

Huntington's disease (HD) is a neurodegenerative disease characterized by prominent loss of neurons in the striatum and cortex. Traditionally research in HD has focused on brain changes as they cause progressive motor dysfunction, cognitive decline and psychiatric disorders. The discovery that huntingtin protein (HTT) and its mutated form (mHTT) are expressed not only in the brain but also in different organs and tissues paved the way for the hypothesis that HD might affect regions beyond the central nervous system (CNS). Besides pathological deposition of mHTT, other mechanisms, including inflammation, seem to underlie HD pathogenesis and progression. Altered inflammation can be evidenced even before the onset of classical symptoms of HD. Herein, we will discuss current pre-clinical and clinical evidence on immune/inflammatory changes in peripheral organs during HD development and progression. The understanding of the impact of inflammation on peripheral organs may open new venues for the development of novel therapeutic targets in HD.
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http://dx.doi.org/10.1016/j.jneuroim.2020.577380DOI Listing
November 2020

Altered Serum Levels of Renin-Angiotensin System Markers in Migraine.

Headache 2020 Oct 2;60(9):1995-2002. Epub 2020 Sep 2.

Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.

Objective: To compare the serum levels of renin-angiotensin system (RAS) components between patients with migraine and healthy controls, and to evaluate whether these levels are associated with migraine severity. We hypothesized that migraine would be associated with the activation of the inflammatory arm of the RAS, possibly leading to increased levels of angiotensin (Ang) II.

Background: Recent studies have proposed the use of drugs that interfere with RAS, a hormonal system primarily implicated in blood pressure regulation, as a prophylactic strategy for migraine. However, no previous studies have directly assessed RAS components in migraine.

Methods: This was a cross-sectional study involving 30 patients with episodic migraine who were in the interictal period and 20 healthy controls. This study was conducted at Hospital das Clínicas (Universidade Federal de Minas Gerais, Belo Horizonte, Brazil) outpatient clinic. Headache severity was evaluated using the Headache Impact Test, version 6 (HIT-6) and the Migraine Disability Test (MIDAS) questionnaires. Given that migraine is comorbid with mood disorders, depressive and anxious symptoms were evaluated using the Beck Anxiety and Depression Inventories (BDI and BAI), respectively. Clinical and demographic data were also collected. Serum levels of angiotensin-converting enzyme (ACE), ACE2, Ang II, and Ang (1-7) were measured by enzyme-linked immunosorbent assay.

Results: Patients with migraine and controls were comparable in age, body mass index, blood pressure, and depressive and anxious symptoms. Patients with migraine showed lower levels of ACE [85.2 (66.8, 101.2) vs 65.5 (54.2, 77.5); P = .005] and lower ACE/ACE2 ratio [4.3 (3.4, 5.2) vs 3.5 (2.9, 4.1); P = .032] than controls. Conversely, patients with migraine had higher levels of Ang II [309.7 ± 147.4 vs 605.4 ± 200.4; difference: -287.1 (95% CI: -391.4--182.8), P < .001] and Ang (1-7) [214.4 ± 155.8 vs 397.9 ± 217.9; difference: -184.6 (95% CI: -296.7--72.6), P = .001] than controls. There were no correlations between RAS serum markers and migraine severity scores (HIT and MIDAS) or depressive and anxious symptoms (BDI and BAI) (P > .05).

Conclusions: Altogether, our results suggest the participation of RAS in migraine pathophysiology, but not in its severity.
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http://dx.doi.org/10.1111/head.13949DOI Listing
October 2020

Coronavirus Disease-2019 Conundrum: RAS Blockade and Geriatric-Associated Neuropsychiatric Disorders.

Front Med (Lausanne) 2020 11;7:515. Epub 2020 Aug 11.

Instituto de Ensino e Pesquisa Santa Casa BH, Belo Horizonte, Brazil.

Coronavirus Disease 2019 (COVID-19) is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which primarily targets the human respiratory system and may lead to severe pneumonia and ultimately death. Mortality rate is particurlarly high among people beyond the sixth decade of life with cardiovascular and metabolic diseases. The discovery that the SARS-CoV-2 uses the renin-angiotensin system (RAS) component ACE2 as a receptor to invade host epithelial cells and cause organs damage resulted in a debate regarding the role of ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) therapies during COVID-19 pandemic. Some authors proposed the discontinuation of ACEIs and ARBs for cardiovascular, kidney, and metabolic diseases, while expert opinions have discouraged that due to limited empirical evidence of their negative effect on COVID-19 outcomes, and that withdrawing treatment may contribute to clinical decompensation in high-risk patients. Moreover, as cardiovascular and metabolic diseases are associated with neurodegenerative and psychiatric disorders, especially among older adults, a critical appraisal of the potential positive effects of ACEIs and ARBs is highly needed. Herein, we aim to discuss the conundrum of ACEIs and ARBs use in high-risk patients for COVID-19, and their potential protective role on the development and/or progression of geriatric neuropsychiatric disorders.
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http://dx.doi.org/10.3389/fmed.2020.00515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431869PMC
August 2020

Peripheral levels of sST2 are increased in patients with temporal lobe epilepsy: Additional evidence of low-grade inflammation.

Epilepsy Behav 2020 11 23;112:107351. Epub 2020 Aug 23.

Santa Casa BH Instituto de Ensino e Pesquisa, Belo Horizonte, MG, Brazil; Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, School of Medicine, University of Texas Health Science Center at Houston, TX, USA.

Inflammation plays a pivotal role in temporal lobe epilepsy (TLE) pathophysiology. IL-33 can act as a transcription factor or as a cytokine, the latter through the transmembrane ST2 receptor or its soluble isoform (sST2), presenting a dual role in neurological diseases. The aim of this study was to determine the plasma levels of IL-33 and sST2 in parallel with clinical features in patients with TLE. Peripheral blood from patients and controls was sampled for the measurement of plasma levels of IL-33 and sST2 by enzyme-linked immunoassay (ELISA). While there were similar levels of IL-33 between controls and patients, sST2 were increased in patients. IL33 and sST2 plasma levels were not associated with TLE-related clinical features. In a subgroup analysis, IL-33 levels correlated with memory performance. In conclusion, our results reinforce the concept of chronic low-grade inflammation in patients with TLE.
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http://dx.doi.org/10.1016/j.yebeh.2020.107351DOI Listing
November 2020

Neuroinflammation is associated with reduced SOCS2 and SOCS3 expression during intracranial HSV-1 infection.

Neurosci Lett 2020 09 13;736:135295. Epub 2020 Aug 13.

Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, School of Medicine, University of Texas Health Science Center at Houston, TX, United States.

Herpes simplex virus type 1 (HSV-1) is the main etiological agent of acute and sporadic encephalitis. Proteins of the suppressor of cytokine signaling (SOCS) family have shown to regulate the inflammation during HSV-1 infection in the brain. However, the effects of SOCS2 and SOCS3 in viral encephalitis remain unclear. The aim of the current study is to investigate the potential association between SOCS2, SOCS3, cytokines, and hippocampal damage, especially neuronal apoptosis, during acute intracranial HSV-1 infection in mice. Male C57BL/6 mice were infected by intracranial route with 10 plaque-forming units (PFU) inoculum of purified HSV-1. At three days post-infection (3 d.p.i.), mice were euthanized and their hippocampi were collected for histopathological analysis, immunohistochemical reaction against active caspase-3 and quantification of SOCS2, SOCS3 and cytokines (tumoral necrosis factor (TNF), interleukin (IL) 1β, IL-6, IL-10; interferon (IFN) -α, IFN-β, IFN-γ) mRNA expression. Infected mice exhibited neuronal loss and hemorrhagic focus in Cornu Ammonis (CA) region. The apoptotic index was higher in infected mice compared to controls. HSV-1 infection was associated with increased hippocampal expression of TNF, IL1-β, IL-6 and IFNα/IFNβ and decreased expression of IL-10, IFN-γ, SOCS2 and SOCS3. Our results suggest that down regulation of SOCS2 and SOCS3 contributes to a pro-inflammatory environment associated with hippocampal damage and neuronal apoptosis during acute HSV-1 infection in mice.
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http://dx.doi.org/10.1016/j.neulet.2020.135295DOI Listing
September 2020