RESUMEN
BACKGROUND: Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by the progressive emergence of multiple cognitive deficits. Early diagnosis is of great significance for the intervention and treatment of AD. The objective of this study is to explore the relationship between cerebral blood perfusion, neuronal cytokines and cognitive function in patients with AD. METHODS: AD patients admitted to the 903 Hospital of the People's Liberation Army Joint Logistics Support Force from June 2020 to January 2023 were retrospectively selected as the study objects, and 65 healthy people who underwent physical examination during the same period were included in the control group. Subjects in both groups underwent 3.0 T magnetic resonance imaging (MRI) to observe their cerebral blood perfusion parameters. The level of cognitive function in both groups was assessed using the Montreal Cognitive Assessment (MoCA). Venous blood was collected from both groups, and the serum levels of brain-derived neuronal factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) were measured by enzyme-linked immunosorbent assay (ELISA). The correlation of serum BDNF and GDNF levels with cerebral blood perfusion parameters and MoCA score in the AD group was analyzed using Spearman analysis. RESULTS: The cerebral blood flow signal intensity of the left frontal lobe, right frontal lobe, left temporal lobe, right temporal lobe, left parietal lobe, right parietal lobe, left occipital lobe, and right occipital lobe of the observation group was significantly lower than that of the control group (p < 0.001). The visuospatial, executive functions, naming, attention, language function, abstract generalization ability, memory ability, orientation, and total MoCA scale scores were significantly lower than those of the control group (p < 0.001). The serum levels of BDNF and GDNF in the observation group were significantly lower than those in the control group (p < 0.001). The results of Spearman analysis showed that cerebral blood perfusion parameters of the left frontal lobe, right frontal lobe, left temporal lobe, right temporal lobe, left parietal lobe, right parietal lobe, left occipital lobe, and right occipital lobe were positively correlated with cognitive function scores in AD patients, serum BDNF and GDNF levels were positively correlated with cognitive function scores in AD patients, and the correlation was statistically significant (p < 0.05). CONCLUSION: In AD patients, blood perfusion parameters and serum BDNF and GDNF levels were significantly lower than those of healthy people. Cerebral blood perfusion parameters of the left frontal lobe, right frontal lobe, left temporal lobe, right temporal lobe, left parietal lobe, right parietal lobe, left occipital lobe, and right occipital lobe, and BDNF and GDNF levels were positively correlated with cognitive function scores in AD patients.
Asunto(s)
Enfermedad de Alzheimer , Factor Neurotrófico Derivado del Encéfalo , Circulación Cerebrovascular , Cognición , Humanos , Masculino , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/fisiopatología , Femenino , Cognición/fisiología , Circulación Cerebrovascular/fisiología , Anciano , Factor Neurotrófico Derivado del Encéfalo/sangre , Estudios Retrospectivos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Factor Neurotrófico Derivado de la Línea Celular Glial/sangre , Citocinas/sangre , Estudios de Casos y Controles , Pruebas de Estado Mental y DemenciaRESUMEN
Major depressive disorder (MDD) is a debilitating illness that includes depressive mood. Repetitive Transcranial Magnetic Stimulation (rTMS) is a therapy method used in the treatment of MDD. The purpose of this study was to assess neurotrophic factors, and oxidative stress levels in MDD patients and evaluate the changes in these parameters as a result of rTMS therapy. Twenty-five patients with MDD and twenty-six healthy volunteers with the same demographic characteristics were included in the study. Brain-derived neurotrophic factors were measured photometrically with commercial kits. Oxidative stress parameters were measured by the photometric method. Oxidative stress index (OSI) and disulfide (DIS) levels were calculated with mathematical formulas. In this study, total antioxidant status (TAS), total thiol (TT), and native thiol (NT) antioxidant parameters and brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and allopregnanolone (ALLO) levels were reduced in pre-rTMS with regard to the healthy control group; TOS, OSI, DIS, and S100 calcium-binding protein B (S100B) levels were increased statistically significantly (p < 0.01). Moreover, owing to TMS treatment; TAS, TT, NT, BDNF, GDNF, and ALLO levels were increased compared to pre-rTMS, while DIS, TOS, OSI, and S100B levels were decreased significantly (p < 0.01). The rTMS treatment reduces oxidative stress and restores thiol-disulfide balance in MDD patients. Additionally, rTMS modulates neurotrophic factors and neuroactive steroids, suggesting its potential as an antidepressant therapy. The changes in the biomarkers evaluated may help determine a more specific approach to treating MDD with rTMS therapy.
Asunto(s)
Factor Neurotrófico Derivado del Encéfalo , Trastorno Depresivo Mayor , Estrés Oxidativo , Estimulación Magnética Transcraneal , Humanos , Trastorno Depresivo Mayor/terapia , Trastorno Depresivo Mayor/sangre , Masculino , Femenino , Adulto , Estimulación Magnética Transcraneal/métodos , Estudios de Casos y Controles , Factor Neurotrófico Derivado del Encéfalo/sangre , Persona de Mediana Edad , Subunidad beta de la Proteína de Unión al Calcio S100/sangre , Factor Neurotrófico Derivado de la Línea Celular Glial/sangre , Antioxidantes/metabolismo , Compuestos de Sulfhidrilo/sangreRESUMEN
Lichen simplex chronicus (LSC) presents a challenge in dermatology due to its elusive pathogenic mechanisms. While associations between circulating inflammatory cytokines and LSC were observed, the definitive causal dynamics remain to be elucidated. Our study used a two-sample Mendelian randomization (MR) approach to investigate causal relationships. We applied a suite of MR methodologies, including IVW, Weighted Median, MR-Egger, Weighted Mode, Simple Mode, MR-PRESSO, and the Steiger test, to ensure robust causal inference. Our analysis confirmed the causal impact of genetically determined cytokine levels on LSC risk, particularly MMP-10 (OR = 0.493, P = 0.004) and DNER (OR = 0.651, P = 0.043) in risk attenuation. We also found a positive causal correlation between GDNF levels (OR = 1.871, P = 0.007) and LSC prevalence. Notably, bidirectional causality was observed between DNER and LSC. Consistency across various MR analyses and sensitivity analyses confirmed the absence of horizontal pleiotropy, validating the causal estimates. This pioneering MR investigation unveils a novel genetically anchored causal relationship between the circulating levels of MMP-10, DNER, and GDNF and LSC risk. Although further validation is requisite, our findings augment the understanding of cytokine mediation in LSC and underscore prospective avenues for research.
Asunto(s)
Citocinas , Factor Neurotrófico Derivado de la Línea Celular Glial , Análisis de la Aleatorización Mendeliana , Neurodermatitis , Humanos , Citocinas/sangre , Citocinas/genética , Neurodermatitis/genética , Neurodermatitis/epidemiología , Factor Neurotrófico Derivado de la Línea Celular Glial/genética , Factor Neurotrófico Derivado de la Línea Celular Glial/sangre , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Factores de RiesgoRESUMEN
BACKGROUND: The glial cell line-derived neurotrophic factor (GDNF) has an important role in neurons and is closely associated with psychiatric disorders. The development of bipolar disorder (BD) may differ between genders. Existing studies have shown that plasma GDNF levels are altered in patients with BD. In this study, we investigate whether the GDNF levels in patients with BD differ in terms of gender. METHODS: Participants were divided into the BD group (n = 76, with 26 males and 50 females) and healthy control (HC) group (n = 89, with 35 males and 54 females). Plasma GDNF levels were detected via multifactor assay. Clinical symptoms of patients with BD were collected and assessed using the Hamilton Depression-17 Inventory, Hamilton Anxiety-17 Inventory, Young's Mania Rating Scale, and Brief Psychiatric Rating Scale. RESULTS: The GDNF levels were significantly higher in all participants in the HC group (F = 4.262, p < 0.05) compared with those in the BD group. In the HC group, the males (t = 4.814, p < 0.001) presented significantly higher levels than the females. The plasma GDNF levels in males in the BD group (t = 3.022, p < 0.05) were significantly lower than those in males in the HC group. CONCLUSION: Differences in plasma GDNF levels are associated with the gender of patients with BD.
Asunto(s)
Trastorno Bipolar , Factor Neurotrófico Derivado de la Línea Celular Glial , Femenino , Humanos , Masculino , Factor Neurotrófico Derivado de la Línea Celular Glial/sangre , Caracteres SexualesRESUMEN
Objectives: We assessed the potential of glial cell line-derived neurotrophic factor (GDNF) as a useful biomarker to predict cirrhosis in chronic hepatitis B (CHB) patients. Methods: A total of 735 patients from two medical centers (385 CHB patients and 350 healthy controls) were included to determine the association of serum and tissue GDNF levels with biopsy-proven cirrhosis. The diagnostic accuracy of serum GDNF (sGDNF) was estimated and compared with other indices of cirrhosis. Results: We showed significantly higher levels of sGDNF in CHB patients with fibrosis (28.4 pg/ml vs. 11.6 pg/ml in patients without) and patients with cirrhosis (33.8 pg/ml vs. 23.5 pg/ml in patients without). The areas under receiver operating curve (AUROCs) of sGDNF were 0.83 (95% confidence interval (CI): 0.80-0.87) for predicting liver fibrosis and 0.84 (95% CI: 0.79-0.89) for cirrhosis. Findings from the serum protein level and hepatic mRNA expression were consistent. Using the best cutoff to predict cirrhosis, we categorized the patients into sGDNF-high and sGDNF-low groups. The sGDNF-high group had significantly larger Masson's trichrome and reticulin staining-positive area, higher Scheuer score, and METAVIR fibrosis stage (all p < 0.001) but not steatosis. On multivariable regression, sGDNF was independently associated with cirrhosis with an odds ratio of 6.98 (95% CI: 1.10-17.94). Finally, we demonstrated that sGDNF outperformed AST to platelet ratio index, FIB-4, fibroscore, forn index, and fibrometer in differentiating F4 vs. F3. Conclusion: Using serum, tissue mRNA, and biopsy data, our study revealed a significant potential of sGDNF as a novel noninvasive biomarker for cirrhosis in CHB patients.
Asunto(s)
Factor Neurotrófico Derivado de la Línea Celular Glial , Hepatitis B Crónica , Cirrosis Hepática , Aspartato Aminotransferasas , Biomarcadores/sangre , Biopsia , Factor Neurotrófico Derivado de la Línea Celular Glial/sangre , Hepatitis B Crónica/sangre , Humanos , Cirrosis Hepática/sangre , Cirrosis Hepática/virología , Recuento de Plaquetas , ARN Mensajero , Curva ROC , Estudios RetrospectivosRESUMEN
Background: Turner syndrome (TS) presents a high risk of congenital heart defects and may predispose to both obesity and related metabolic complications. Hence the search for new markers as potential early predictors of the metabolic syndrome (MetS) and cardiovascular diseases appears warranted. Objective: To assess MMP-1 (matrix metalloproteinase-1), MMP-2 (matrix metalloproteinase-2), MMP-9 (matrix metallopeptidase-9), BDNF (brain-derived neurotrophic factor), GDNF (glial cell line-derived neurotrophic factor), and VEGF (vascular endothelial growth factor) in non-MetS TS girls not treated with growth hormone (GH) vs. healthy short stature girls, and to assess the connection with basic metabolic parameters. Method: The concentrations of circulating MMP-1, MMP-2, MMP-9, BDNF, GDNF and VEGF were measured in 12 patients with TS not treated with growth hormone. The control group was composed of 17 girls with non-pathologic short stature. The patients' clinical and biochemical phenotypes were determined by weight, height, total cholesterol, HDL cholesterol, triglycerides, glucose, aminotransferases, IGF1, TSH and fT4. Results: There were no differences in mean age, weight, BMI Z-Score, or hSDS between the studied group and the controls; however, they differed in baseline values of ALT (18.2 ± 4.2 vs. 14.2 ± 4.1, p= 0.02), BDNF [29951.5 (26176.9 - 41271.9) vs. 23131.7 (18392.4 - 28313.3), p=0.01] and MMP-2 [91.8 (71.7 - 111.0) vs. 143.6 (123.7 - 244.5), p< 0.001]. BDNF correlated with ALT activity (r = 0.56 p = 0.002) and BMI Z-score (r = 0.38 p = 0.042), while MMP-2 correlated with HDL concentration (r = 0.48 p = 0.029) in all the patients. The analysis of the study group alone revealed significant positive correlations between MMP-9 and TSH (r = 0.74 p = 0.036), BDNF and both ALT (r = 0.73 p = 0.038) and TSH (r = 0.85 p = 0.008), and a negative correlation between MMP-1 and fT4 (r = -0.75 p = 0.032). The control group did not present any significant correlations. Conclusion: The higher concentrations of BDNF and lower of MMP-2 found in girls with TS without MetS compared to healthy girls with short stature, could have a major impact on the future "natural" development of the metabolic status. Our findings need further studies.
Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/sangre , Metaloproteinasas de la Matriz/sangre , Síndrome de Turner/metabolismo , Factor A de Crecimiento Endotelial Vascular/sangre , Adolescente , Biomarcadores/sangre , Índice de Masa Corporal , Estudios de Casos y Controles , Niño , Preescolar , Metabolismo Energético/fisiología , Femenino , Factor Neurotrófico Derivado de la Línea Celular Glial/sangre , Humanos , Síndrome de Turner/sangreRESUMEN
Individualized patient care is essential to reduce the global burden of traumatic brain injury (TBI). This pilot study focused on TBI patients admitted to intensive care units (ICUs) and aimed at identifying patterns of circulating biomarkers associated with the disability level at 6 months from injury, measured by the extended Glasgow Outcome Scale (GOS-E). The concentration of 107 biomarkers, including proteins related to inflammation, innate immunity, TBI, and central nervous system, were quantified in blood samples collected on ICU admission from 80 patients. Patients were randomly selected among those prospectively enrolled in the Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe (CREACTIVE) observational study. Six biomarkers were selected to be associated with indicators of primary or secondary brain injury: three glial proteins (glial cell-derived neurotrophic factor, glial fibrillary acidic protein, and S100 calcium-binding protein B) and three cytokines (stem cell factor, fibroblast growth factor [FGF] 23 and FGF19). The subjects were grouped into three clusters according to the expression of these proteins. The distribution of the 6-month GOS-E was significantly different across clusters (p < 0.001). In two clusters, the number of 6-month deaths or vegetative states was significantly lower than expected, as calculated according to a customization of the corticosteroid randomization after significant head injury (CRASH) scores (observed/expected [O/E] events = 0.00, 95% confidence interval [CI]: 0.00-0.90 and 0.00, 95% CI: 0.00-0.94). In one cluster, less-than-expected unfavorable outcomes (O/E = 0.50, 95% CI: 0.05-0.95) and more-than-expected good recoveries (O/E = 1.55, 95% CI: 1.05-2.06) were observed. The improved prognostic accuracy of the pattern of these six circulating biomarkers at ICU admission upon established clinical parameters and computed tomography results needs validation in larger, independent cohorts. Nonetheless, the results of this pilot study are promising and will prompt further research in personalized medicine for TBI patients.
Asunto(s)
Lesiones Traumáticas del Encéfalo/sangre , Lesiones Traumáticas del Encéfalo/mortalidad , Citocinas/sangre , Factor Neurotrófico Derivado de la Línea Celular Glial/sangre , Proteína Ácida Fibrilar de la Glía/sangre , Subunidad beta de la Proteína de Unión al Calcio S100/sangre , Adulto , Biomarcadores/sangre , Lesiones Traumáticas del Encéfalo/diagnóstico , Estudios de Cohortes , Cuidados Críticos , Enfermedad Crítica , Europa (Continente) , Femenino , Escala de Consecuencias de Glasgow , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Valor Predictivo de las Pruebas , PronósticoRESUMEN
Sympathetic activation may trigger acute coronary syndromes. We examined the relation between circulating neurotrophic factors and hemostatic risk factors of atherothrombotic cardiovascular disease at baseline and in response to acute mental stress to establish a brain-heart link. In 409 black and white South Africans, brain-derived neurotrophic factor (BDNF) and fibrinolytic measures were assessed at baseline. Glial cell-derived neurotrophic factor (GDNF), S100 calcium-binding protein (S100B), von Willebrand factor (VWF), fibrinogen and D-dimer were assessed at baseline and 10 min after the Stroop test. Neurotrophins were regressed on hemostatic measures adjusting for demographics, comorbidities, cardiometabolic factors and health behaviors. Higher baseline BDNF was associated with greater stress-induced increase in fibrinogen (p = 0.003) and lower D-dimer increase (p = 0.016). Higher baseline S100B was significantly associated with higher baseline VWF (p = 0.031) and lower fibrinogen increase (p = 0.048). Lower baseline GDNF was associated with higher baseline VWF (p = 0.035) but lower VWF increase (p = 0.001). Greater GDNF (p = 0.006) and S100B (p = 0.042) increases were associated with lower VWF increase. All associations showed small-to-moderate effect sizes. Neurotrophins and fibrinolytic factors showed no significant associations. The findings support the existence of a peripheral neurothrophin-hemostasis interaction of small-to-moderate clinical relevance. The implications for atherothrombotic cardiovascular disease need further exploration.
Asunto(s)
Enfermedades Cardiovasculares/sangre , Factores de Crecimiento Nervioso/sangre , Adulto , Población Negra , Femenino , Fibrinógeno/metabolismo , Factor Neurotrófico Derivado de la Línea Celular Glial/sangre , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Factor de von Willebrand/metabolismoRESUMEN
Glial cell line-derived neurotrophic factor (GDNF) may play an important role in attention. We investigated the association between serum GDNF levels and clinical status in unmedicated adults with attention deficit/hyperactivity disorder (ADHD) (n = 16) and healthy controls (n = 33); the levels were comparable between the ADHD and control groups (107.2 ± 31.7 vs. 110.5 ± 40.0 pg/mL, respectively; p = 0.77). In the ADHD group, higher GDNF serum levels were associated with severe subjective inattention (r = 0.528, p = 0.035). These preliminary results suggest that the serum GDNF level may not be a suitable biomarker for adult ADHD, although it may be associated with the pathophysiology of persistent inattention in adult ADHD.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/sangre , Factor Neurotrófico Derivado de la Línea Celular Glial/sangre , Adulto , Biomarcadores/sangre , Factor Neurotrófico Derivado del Encéfalo/sangre , Cognición , Femenino , Humanos , MasculinoRESUMEN
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, 1ß, 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(1,43) = 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.
Asunto(s)
Trastorno Bipolar/terapia , Factor Neurotrófico Derivado del Encéfalo/sangre , Citocinas/sangre , Factor Neurotrófico Derivado de la Línea Celular Glial/sangre , Plasticidad Neuronal/fisiología , Estimulación Transcraneal de Corriente Directa , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Trastorno Bipolar/sangre , Trastorno Bipolar/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Corteza Prefrontal/fisiopatología , Resultado del Tratamiento , Adulto JovenRESUMEN
Nowadays depression is considered as a systemic illness with different biological mechanisms involved in its etiology, including inflammatory response, hypothalamic-pituitary-adrenal (HPA) axis dysregulation and neurotransmitter and neurotrophic systems imbalance. Novel "omics" approaches, such as metabolomics and glycomics provide information about altered metabolic pathways and metabolites, as well as disturbances in glycosylation processes affected by or causing the development of depression. The clinical diagnosis of depression continues to be established based on the presence of the specific symptoms, but due to its heterogeneous underlying biological background, that differs according to the disease stage, there is an unmet need for treatment response biomarkers which would facilitate the process of appropriate treatment selection. This paper provides an overview of the role of major stress response system, the HPA axis, and its dysregulation in depression, possible involvement of neurotrophins, especially brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor and insulin-like growth factor-1, in the development of depression. Article discusses how activated inflammation processes and increased cytokine levels, as well as disturbed neurotransmitter systems can contribute to different stages of depression and could specific metabolomic and glycomic species be considered as potential biomarkers of depression. The second part of the paper includes the most recent findings about available medical treatment of depression. The described biological factors impose an optimistic conclusion that they could represent easy obtainable biomarkers potentially predicting more personalized treatment and diagnostic options.
Asunto(s)
Biomarcadores/sangre , Trastorno Depresivo/diagnóstico , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipófiso-Suprarrenal/metabolismo , Factor Neurotrófico Derivado del Encéfalo/sangre , Citocinas/sangre , Trastorno Depresivo/sangre , Trastorno Depresivo/terapia , Factor Neurotrófico Derivado de la Línea Celular Glial/sangre , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , MetabolómicaRESUMEN
Neurotrophins are signalling molecules involved in the formation and maintenance of synapses in the brain. They can cross the blood-brain barrier and be detected in peripheral blood, suggesting they may be a potential biomarker for brain health and function. In this review, the available literature was systematically searched for studies comparing peripheral neurotrophins levels with MRI and cognitive measures in healthy adults. Twenty-four studies were identified, six of which included a neuroimaging outcome. Fifteen studies measuring cognition were eligible for meta-analysis. The majority of studies measured levels of brain-derived neurotrophic factor (BDNF), with few assessing other neurotrophins. Results revealed BDNF is related to some neuroimaging outcomes, with some studies suggesting older age may be an important factor. A higher proportion of studies who had older samples observed significant effects between cognition and neurotrophin levels. When cognitive studies were pooled together in a meta-analysis, there was a weak non-significant effect between BDNF and cognitive outcomes. There was also a high level of heterogeneity between cognitive studies. Results indicated that gender was a notable source of the heterogeneity, but additional studies employing relevant covariates are necessary to better characterise the inter-relationship between circulating neurotrophins and cognition.
Asunto(s)
Encéfalo/metabolismo , Cognición/fisiología , Factores de Crecimiento Nervioso/sangre , Biomarcadores/sangre , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Factor Neurotrófico Derivado del Encéfalo/sangre , Factor Neurotrófico Ciliar/sangre , Factor Neurotrófico Derivado de la Línea Celular Glial/sangre , Humanos , Neurotrofina 3/sangre , Factores de Crecimiento Transformadores/sangreRESUMEN
BACKGROUND: Stroke is a major cause of death and disability worldwide. Among its complications, post-stroke depression (PSD) leads to a significant burden. The diagnosis of PSD is complex, and there are no biomarkers that can assist in its early identification and adequate management. OBJECTIVE: The aim of the present study is to investigate peripheral biomarkers in the acute phase of stroke and their potential association with depressive symptoms. METHODS: We evaluated 60 patients in the acute phase of stroke by using standardized instruments of psychiatric and neurological assessment (Mini International Neuropsychiatric Interview-Plus- MINI-Plus, Hospital Anxiety and Depression Scale-HADS, and National Institutes of Health Stroke Scale-NIHSS) and measured peripheral biomarkers. RESULTS: In multivariate analysis, low peripheral levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and higher NIHSS scores were associated with PSD. The severity of depressive symptoms was inversely correlated with sTREM-1 and glial cell-derived neurotrophic factor (GDNF) levels. CONCLUSION: This is the first study indicating an association between sTREM-1 and PSD. Our results may point to the involvement of glial mechanisms in the manifestation of depressive symptoms after stroke.
Asunto(s)
Depresión/sangre , Depresión/diagnóstico , Factor Neurotrófico Derivado de la Línea Celular Glial/sangre , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/diagnóstico , Receptor Activador Expresado en Células Mieloides 1/sangre , Anciano , Biomarcadores/sangre , Estudios Transversales , Depresión/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Accidente Cerebrovascular/complicacionesRESUMEN
Objective: The aim of this study was to identify potential differences in serum brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), nerve growth factor (NGF) and neurotrophin-3 (NTF3) levels in adolescents with major depressive disorder (MDD) compared to healthy controls. The possible relationship between serum neurotrophin levels and suicidality in adolescents with MDD was also addressed.Methods: A total of 70 treatment-free adolescents with MDD and 40 healthy controls aged 11 to 19 years were enrolled. The severity of suicidality was determined using the Columbia-Suicide Severity Rating Scale, and the severity of depression and anxiety symptoms were evaluated by self-report inventories. Serum levels of neurotrophins were measured using an enzyme-linked immunosorbent assay.Results: The mean serum BDNF levels were significantly higher in adolescents with MDD than in control subjects; no significant difference was found between the groups for serum GDNF, NGF and NTF3 levels. No correlations were found between the levels of serum neurotrophins and the severity of depression or suicidality.Conclusions: The study results suggest that elevated serum BDNF levels may be related to MDD in adolescents. However, our findings did not support a role for neurotrophins in suicidality.Key pointsSerum BDNF levels were higher in adolescents with MDD than in controls.No significant alterations of serum levels of GDNF, NGF and NTF3 were evident in adolescents with MDD.Neurotrophin levels were not associated with suicidal ideation and behaviours.
Asunto(s)
Conducta del Adolescente/fisiología , Factor Neurotrófico Derivado del Encéfalo/sangre , Trastorno Depresivo Mayor/sangre , Trastorno Depresivo Mayor/fisiopatología , Factor Neurotrófico Derivado de la Línea Celular Glial/sangre , Factor de Crecimiento Nervioso/sangre , Neurotrofina 3/sangre , Ideación Suicida , Intento de Suicidio , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
The present study aims to discuss the effect of escitalopram in glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF) levels, and 5-Hydroxytryptamine (5-HT) in obsessive-compulsive disorder rats. A total of 42 rats were divided into three groups randomly: control group (n = 14), model group (n = 14) (obsessive-compulsive disorder group), and escitalopram group (n = 14) (model + obsessive-compulsive disorder group + escitalopram treatment). The open-field method was used to test the rat behavior, enzyme-linked immunosorbent assay (ELISA) was used to determine the serum GDNF and BDNF levels. In addition, Western blot was used to determine the brain tissue protein levels of GDNF and BDNF and high-performance liquid chromatography + electrochemistry method to determine the 5-HT level of brain tissue. Visiting place was changed, rotational frequency and fixed duration enhanced in escitalopram group compared to model group (P < 0.05). Besides, GDNF and BDNF levels of serum and brain tissue were decreased in model group and escitalopram group compared to control group (P < 0.05), while GDNF and BDNF levels of serum and brain tissue were increased in escitalopram group compared to model group (P < 0.05). Moreover, the 5-HT level of brain tissue in escitalopram group was higher than that in model group (P < 0.05). Escitalopram could increase GDNF and BDNF levels and 5-HT content in serum and brain tissue in obsessive-compulsive disorder rats, which contributes to a function on the treatment of obsessive-compulsive disorder.
Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/sangre , Encéfalo/metabolismo , Citalopram/farmacología , Factor Neurotrófico Derivado de la Línea Celular Glial/sangre , Trastorno Obsesivo Compulsivo/sangre , Serotonina/metabolismo , Animales , Conducta Animal/efectos de los fármacos , Ratas WistarRESUMEN
OBJECTIVES: Mild cognitive impairment is a common non-motor feature of Parkinson's disease, termed PD-MCI. But there is a scarcity of data on the role of glial cell line-derived neurotrophic factor (GDNF) and neurotransmitters in pathogenesis of PD-MCI. The aim of this project was to detect the serum levels of GDNF and multiple neurotranmitters and explore their relationships with cognitive performance in PD-MCI patients. METHODS: Neuropsychological testing was administered to PD patients and healthy controls to investigate different domains of cognitive function. Serum levels of GDNF and four cognition-related neurotransmitters including Dopamine metabolites Homovanillic acid (HVA), acetylcholine (Ach), γ-aminobutyric acid (GABA) and 5-hydroxytryptamine (5-HT) were detected by enzyme-linked immunosorbent assay and liquid chromatography-electrospray ionization tandem mass spectrometry analysis respectively. RESULTS: The more serious cognitive impairment of PD, the lower levels of GDNF, HVA and 5-HT. In PD-MCI patients, the levels of GDNF, HVA, Ach, 5-HT, and GABA had a significant positive correlation with Digit span backward test (DSB-T) scores and negative correlation with the scores of Trail Making Test A (TMT-A) and Trail Making Test B (TMT-B) respectively. Effect size analysis showed that GDNF and GDNF*Ach have a significant effect on DSB-T, TMT-A and TMT-B respectively; GDNF*HVA, GDNF*5-HT and GDNF*GABA play important part in Auditory Verbal Learning Test separately. CONCLUSIONS: Serum GDNF may be involved in the impairment of attention, memory and executive function of PD-MCI patients, by acting alone or in conjunction with neurotransmitters (HVA, 5-HT, GABA, and Ach).
Asunto(s)
Disfunción Cognitiva/fisiopatología , Factor Neurotrófico Derivado de la Línea Celular Glial/sangre , Neurotransmisores/sangre , Enfermedad de Parkinson/psicología , Anciano , Estudios de Casos y Controles , Disfunción Cognitiva/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Enfermedad de Parkinson/sangreRESUMEN
Physical exercise has a neuromodulatory effect on the central nervous system (CNS) partially by modifying expression of neuropeptides produced and secreted by neurons and glial cells, among which the best examined are brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF). Because both neurotrophins can cross the brain-blood barrier (BBB), their blood levels indirectly reflect their production in the CNS. Moreover, both neuropeptides are involved in modulation of dopaminergic and serotoninergic system function. Because limited information is available on the effects of exercise to volition exhaustion and acute hypoxia on CNS, BDNF and GDNF formation, the aims of the present study were to verify whether 1) acute exercise to exhaustion in addition to neurons also activates glial cells and 2) additional exposure to acute normobaric moderate hypoxia affects their function. In this feasibility study we measured blood concentrations of BDNF, GDNF, and neuropeptides considered as biomarkers of brain damage (bFGF, NGF, S100B, GFAP) in seven sedentary healthy young men who performed a graded exercise test to volitional exhaustion on a cycle ergometer under normoxic (N) and hypoxic conditions: 2,000 m (H2; FiO2 = 16.6%) and 3,000 m altitude (H3; FiO2 = 14.7%). In all conditions serum concentrations of both BDNF and GDNF increased immediately after cessation of exercise (p<0.01). There was no effect of condition or interaction (condition x time of measurement) and exercise on any of the brain damage biomarkers: bFGF, NGF, S100B, GFAP. Moreover, in N (0<0.01) and H3 (p<0.05) exercise caused elevated serum 5-HT concentration. The results suggest that a graded effort to volitional exhaustion in normoxia, as well as hypoxia, simultaneously activates both neurons and astrocytes. Considering that s100B, GFAP, bFGF, and NGF (produced mainly by astrocytes) are markers of brain damage, it can be assumed that a maximum effort in both conditions is safe for the CNS.
Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/sangre , Ejercicio Físico/fisiología , Factor Neurotrófico Derivado de la Línea Celular Glial/sangre , Hipoxia/fisiopatología , Neuroglía/metabolismo , Neuronas/metabolismo , Adulto , Células Cultivadas , Estudios de Factibilidad , Humanos , Masculino , Neuroglía/citología , Neuronas/citología , Adulto JovenRESUMEN
BACKGROUND: To measure the serum levels of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) in deficit schizophrenia (DS), in order to examine the association between these two neurotrophic factors (NFs) and cognitive performance. METHODS: A total of 109 male patients [51 DS and 58 non-deficit schizophrenia (NDS)] with schizophrenia and 40 sex and age matched healthy controls (HC) participated in this study. Processing speed, attention, executive function, and working memory of all subjects were assessed by means of a battery of classical neuropsychological tests. Serum BDNF and GDNF levels were measured simultaneously using a double-antibody sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: There were significant differences in the overall cognitive test scores between three groups (all p < 0.001). Serum BDNF levels were significantly lower in patients (DS and NDS) than in HC (p < 0.001). Furthermore, BDNF levels were lower in the DS compared to the NDS group, although not significantly. However, there was no difference in the GDNF levels between patients (DS and NDS) and HC. GDNF levels were positively correlated with scores of Stroop words only (r = 0.311, p = 0.033), Stroop colors only (r = 0.356, p = 0.014) and Stroop interference (r = 0.348, p = 0.016) in DS group. CONCLUSION: Serum BDNF may be an unsuitable biomarker for DS, despite a significant decrease in schizophrenia patients. The different neurocognitive performance between the DS and NDS patients indicates that DS may be a separate clinical entity of schizophrenia. Finally, higher serum GDNF levels are associated with better cognitive performance in DS patients, indicating a possible neuroprotective function in DS.
Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/sangre , Disfunción Cognitiva/sangre , Disfunción Cognitiva/psicología , Factor Neurotrófico Derivado de la Línea Celular Glial/sangre , Esquizofrenia/sangre , Psicología del Esquizofrénico , Adulto , Biomarcadores/sangre , China/epidemiología , Disfunción Cognitiva/epidemiología , Humanos , Masculino , Memoria a Corto Plazo/fisiología , Persona de Mediana Edad , Pruebas Neuropsicológicas , Esquizofrenia/epidemiología , Adulto JovenRESUMEN
Cell therapy raises hope to reduce the harmful effects of acute myocardial ischemia. Stem and progenitor cells (SPCs) may be a valuable source of trophic factors. In this study, we assessed the plasma levels of selected trophic factors in patients undergoing application of autologous bone marrow (BM)-derived, lineage-negative (Lin-) stem/progenitor cells into the coronary artery in the acute phase of myocardial infarction. The study group consisted of 15 patients with acute myocardial infarction (AMI) who underwent percutaneous revascularization and, afterwards, Lin- stem/progenitor cell administration into the infarct-related artery. The control group consisted of 19 patients. BM Lin- cells were isolated using immunomagnetic methods. Peripheral blood was collected on day 0, 2, 4, and 7 and after the first and third month to assess the concentration of selected trophic factors using multiplex fluorescent bead-based immunoassays. We found in the Lin- group that several angiogenic trophic factors (vascular endothelial growth factor, Angiopoietin-1, basic fibroblast growth factor, platelet-derived growth factor-aa) plasma level significantly increased to the 4th day after myocardial infarction. In parallel, we noticed a tendency where the plasma levels of the brain-derived neurotrophic factor were increased in the Lin- group. The obtained results suggest that the administered SPCs may be a valuable source of angiogenic trophic factors for damaged myocardium, although this observation requires further in-depth studies.
Asunto(s)
Inductores de la Angiogénesis/sangre , Linaje de la Célula , Vasos Coronarios/patología , Infarto del Miocardio/sangre , Infarto del Miocardio/terapia , Trasplante de Células Madre , Células Madre/citología , Factor Neurotrófico Derivado del Encéfalo/sangre , Factor Neurotrófico Derivado de la Línea Celular Glial/sangre , Humanos , Persona de Mediana EdadRESUMEN
OBJECTIVE: It has been shown that maternal epilepsy and antiepileptic drug use during pregnancy have adverse developmental outcomes in children. The aim of this study was to investigate the developmental outcomes of maternal epilepsy and prenatal antiepileptic exposure. We also looked for the associations between serum levels of glial cell-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) and developmental outcomes. METHODS: This is a retrospective, nonrandomized, case-controlled study. Fifty-three children aged two to six years old with maternal epilepsy were included in the case group. Fifty-three age- and gender-matched children without maternal epilepsy were included in the control group. Developmental assessment was conducted using the Denver II Developmental Screening Test (DDST-II). Serum levels of NGF and GDNF were measured using an enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: Multiple regression analysis revealed that prenatal antiepileptic exposure was significantly associated with lower global developmental scores (Bâ¯=â¯-7.5, confidence interval (CI): -13.1; -1.9, pâ¯=â¯0.009) while periconceptional folate use was associated with a reduced risk for adverse developmental outcomes (Bâ¯=â¯6.6, CI: 0.91; 12.3, pâ¯=â¯0.024). Children with prenatal antiepileptic exposure are at increased risk for global developmental delay (GDD) particularly for language domain (pâ¯=â¯0.018). We found a statistically significant positive correlation between NGF levels and global developmental scores (râ¯=â¯0.302, pâ¯=â¯0.009). Serum levels of GDNF in children with maternal epilepsy were significantly lower than the children without maternal epilepsy (pâ¯=â¯0.025). CONCLUSIONS: Prenatal antiepileptic exposure was related with the increased risk of GDD while periconceptional folate use was related with lower risk. Clinicians should inform all women in reproductive age with epilepsy about the possible benefits and risks of antiepileptic drug use during a possible pregnancy. Periconceptional folate use has protective effect on child development, and all women on antiepileptic drugs should be encouraged for periconceptional folate use. Serum NGF levels may be a promising biomarker for monitoring global development delay in at-risk population.