RESUMO
OBJECTIVE: This study examined the correlation between serum miR-98-5p levels and indices of microvascular reperfusion in patients undergoing primary percutaneous coronary intervention (pPCI) after ST-segment elevation myocardial infarction (STEMI). Additionally, we evaluated the mechanisms by which miR-98-5p promoted ischemia/reperfusion (I/R)-induced injury in both cultured cell lines and an animal model. METHODS: Circulating miR-98-5p levels were measured and compared from 171 STEMI patients undergoing pPCI, who were divided into two groups: no-reflow and reflow. The levels of miR-98-5p, nerve growth factor (NGF), and transient receptor potential vanilloid 1 (TRPV1) were analyzed in cultured human coronary endothelial cells (HCECs) exposed to hypoxia/reoxygenation (H/R). The effects of antagomir-98-5p on myocardial I/R-induced microvascular dysfunction in vivo were evaluated. Target gene expression and activity were assessed. RESULTS: Higher miR-98-5p levels were associated with compromised indices of microvascular reperfusion. In vitro experiments on HCECs showed that exposure to H/R significantly increased miR-98-5p levels. We identified NGF as a novel target of miR-98-5p. Further, antagomir-98-5p relieved microvascular dysfunction and enhanced the expression of NGF and TRPV1 in the rat myocardial I/R model. CONCLUSIONS: MiR-98-5p promotes microvascular dysfunction by targeting the NGF-TRPV1 axis. Serum miR-98-5p serves as a potential biomarker for microvascular reperfusion.
Assuntos
Vasos Coronários/metabolismo , MicroRNAs/sangue , Microvasos/metabolismo , Traumatismo por Reperfusão Miocárdica/sangue , Fator de Crescimento Neural/sangue , Idoso , Biomarcadores/sangue , Células Cultivadas , Vasos Coronários/patologia , Células Endoteliais/metabolismo , Células Endoteliais/fisiologia , Feminino , Seguimentos , Regulação da Expressão Gênica , Humanos , Masculino , Microvasos/patologia , Pessoa de Meia-Idade , Traumatismo por Reperfusão Miocárdica/patologiaRESUMO
AIM: The aim of this study was to identify biomarkers associated with major depressive disorder (MDD) and conversion from MDD to bipolar disorder (BD) in an outpatient sample of women. METHODS: This was a longitudinal study including women diagnosed with MDD and aged 18 to 60 years. The follow-up was 3 years. The diagnosis was performed using the Mini International Neuropsychiatric Interview Plus. Blood collection was just performed in the first phase. Serum interleukin-6, tumor necrosis factor-α, brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, and nerve growth factor (NGF) levels were measured using a commercial immunoassay kit. RESULTS: We included 156 women. The conversion rate from MDD to BD was 15.4% (n = 24). NGF serum levels were increased in patients who converted to BD compared to the remitted MDD group and current MDD group (P = 0.013). The Bonferroni post-hoc test for multiple comparisons revealed significant differences for higher NGF levels in patients who converted to BD compared to patients with current MDD (P = 0.037). Interleukin-6, tumor necrosis factor-α, brain-derived neurotrophic factor, and glial cell-derived neurotrophic factor serum levels did not differ among the groups. CONCLUSION: Our results suggest that NGF might be a useful biomarker associated with early detection of conversion to BD, helping clinicians in the clinical diagnosis.
Assuntos
Transtorno Bipolar/sangue , Transtorno Depressivo Maior/sangue , Fator de Crescimento Neural/sangue , Adulto , Transtorno Bipolar/psicologia , Fator Neurotrófico Derivado do Encéfalo/sangue , Transtorno Depressivo Maior/psicologia , Feminino , Fator Neurotrófico Derivado de Linhagem de Célula Glial/sangue , Humanos , Interleucina-6/sangue , Estudos Longitudinais , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/sangue , Adulto JovemRESUMO
BACKGROUND: A plethora of reactive cellular responses emerge immediately after a traumatic spinal cord injury (SCI) and may influence the patient's outcomes. We investigated whether serum concentrations of neuron-specific enolase, interleukin-6, glial-derived neurotrophic factor, and neurotrophic growth factor reflect the acute-phase responses to different etiologies of SCI and may serve as predictive biomarkers of neurologic and functional outcomes. METHODS: Fifty-two patients were admitted to the intensive care unit after SCI due to traffic accidents, falls, and firearm wounds and had blood samples collected within 48 hours and 7 days after SCI. Thirty-six healthy subjects with no history of SCI were included as controls. Neurologic and functional status was evaluated on the basis of American Spinal Injury Association and Functional Independence Measure scores over a period of 48 hours and 6 months after SCI. RESULTS: Serum NSE increased significantly 48 hours and 7 days after SCI compared with controls, while interleukin-6 increased only at 48 hours. In contrast, the neurotrophic growth factor level significantly decreased 48 hours and 7 days after SCI. Serum glial-derived neurotrophic factor level did not differ from control at any time point. Also, there was no significant difference in biomarker concentrations between the etiologies of SCI or the level of spinal injury. There were no correlations between biomarker levels at 48 hours with neurologic or functional outcomes 7 days and 6 months after SCI. CONCLUSIONS: Our results suggest expansive axonal damage coupled with an acute proinflammatory response after SCI. However, in our study biomarker concentration did not correlate with short- or long-term prognosis, such as survival rate or sensory and motor function.
Assuntos
Traumatismos da Medula Espinal/sangue , Traumatismos da Medula Espinal/terapia , Adulto , Biomarcadores/sangue , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/lesões , Estudos de Coortes , Feminino , Humanos , Interleucina-6/sangue , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/lesões , Masculino , Pessoa de Meia-Idade , Fator de Crescimento Neural/sangue , Estudos Prospectivos , Traumatismos da Medula Espinal/diagnóstico por imagem , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/lesões , Resultado do Tratamento , Adulto JovemRESUMO
Objective: To correlate neurotrophic factors - brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and beta-nerve growth factor (beta-NGF) - and severity of depressive symptoms in patients diagnosed with major depressive disorder (MDD) undergoing cognitive-behavioral therapy (CBT). Methods: In this quasi-experimental study, participants were selected by convenience and received 16 sessions of CBT. The outcomes of interest were severity of depressive symptoms and changes in neurotrophic factor levels after CBT. The differences between variables before and after treatment (deltas) were analyzed. Results: Patients had significant changes in symptom severity after treatment. No significant associations were found between Beck Depression Inventory II (BDI-II) scores and any independent variable. No correlations were observed between BDNF or GDNF levels and BDI scores before or after treatment, although there was a trend toward significant differences in beta-NGF levels. Conclusion: BDNF, beta-NGF, and GDNF were not influenced by the effects of CBT on depressive symptoms.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Terapia Cognitivo-Comportamental/métodos , Fator Neurotrófico Derivado do Encéfalo/sangue , Fator de Crescimento Neural/sangue , Transtorno Depressivo Maior/sangue , Fator Neurotrófico Derivado de Linhagem de Célula Glial/sangue , Escalas de Graduação Psiquiátrica , Fatores Socioeconômicos , Índice de Gravidade de Doença , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/psicologia , Ensaios Clínicos Controlados não Aleatórios como Assunto , Fatores de Crescimento Neural/sangueRESUMO
OBJECTIVE: To correlate neurotrophic factors - brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and beta-nerve growth factor (beta-NGF) - and severity of depressive symptoms in patients diagnosed with major depressive disorder (MDD) undergoing cognitive-behavioral therapy (CBT). METHODS: In this quasi-experimental study, participants were selected by convenience and received 16 sessions of CBT. The outcomes of interest were severity of depressive symptoms and changes in neurotrophic factor levels after CBT. The differences between variables before and after treatment (deltas) were analyzed. RESULTS: Patients had significant changes in symptom severity after treatment. No significant associations were found between Beck Depression Inventory II (BDI-II) scores and any independent variable. No correlations were observed between BDNF or GDNF levels and BDI scores before or after treatment, although there was a trend toward significant differences in beta-NGF levels. CONCLUSION: BDNF, beta-NGF, and GDNF were not influenced by the effects of CBT on depressive symptoms.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/sangue , Terapia Cognitivo-Comportamental/métodos , Transtorno Depressivo Maior/sangue , Fator Neurotrófico Derivado de Linhagem de Célula Glial/sangue , Fator de Crescimento Neural/sangue , Fatores de Crescimento Neural/sangue , Adulto , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados não Aleatórios como Assunto , Escalas de Graduação Psiquiátrica , Índice de Gravidade de Doença , Fatores Socioeconômicos , Adulto JovemRESUMO
BACKGROUND: Neuropathy is one of the major complications of type 2 diabetes mellitus. Our first aim was to determine the clinical characteristics of a population of diabetic patients with different types of neuropathy. Our next goal was to characterize the cytokine profile (IL-6 and IL-10), nerve growth factor (NGF) and circulating cell-adhesion molecules in these patients. Finally, we aimed to compare the renal function among the groups of neuropathic patients. METHODS: In a cross-sectional study, we included 217 diabetic patients classified in three groups: sensory polyneuropathy with hypoesthesia (DShP) or hyperesthesia (DSHP), and motor neuropathy (DMN). Two control groups were included: one of 26 diabetic non-neuropathic patients (DNN), and the other of 375 non-diabetic (ND) healthy subjects. The participants were attending to the Mexican Institute of Social Security. RESULTS: The circulating levels of NGF were significantly lower in diabetic patients, compared to healthy subjects. The range of IL-6 and IL-10 levels in neuropathic patients was higher than the control groups; however, several samples yielded null measurements. Neuropathic patients also showed increased circulating levels of the adhesion molecules ICAM, VCAM, and E-Selectin, compared to the ND group. Moreover, neuropathic patients showed reduced glomerular filtration rates compared to healthy subjects (82-103 ml/min per 1.73 m2, data as range from 25th-75th percentiles), especially in the group with DMN (45-76 ml/min per 1.73 m2). CONCLUSIONS: Some particular alterations in neuropathic patients included -but were not limited to- changes in circulating NGF, cell adhesion molecules, inflammation, and the worsening of the renal function. This study supports the need for further clinical surveillance and interventions considering a neuropathy-related basis.
Assuntos
Diabetes Mellitus Tipo 2 , Neuropatias Diabéticas , Indígenas Norte-Americanos/estatística & dados numéricos , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Neuropatias Diabéticas/sangue , Neuropatias Diabéticas/epidemiologia , Humanos , Interleucina-10/sangue , Interleucina-6/sangue , México , Fator de Crescimento Neural/sangueRESUMO
The aim of this study was to evaluate the impact of psychoeducation in serum levels of BDNF, NGF and GDNF in young adults presenting bipolar disorder (BD). This is a randomized clinical trial including 39 young adults (18-29 years) diagnosed with BD through the Structured Clinical Interview for DSM-IV (SCID-CV). Participants were randomized in two treatment groups: usual treatment (medication) and combined intervention (medication plus psychoeducation). Depressive symptoms were assessed using the Hamilton Depression Rating Scale (HDRS) and severity of manic and hypomanic symptoms was evaluated through the Young Mania Rating Scale (YMRS). The serum levels of trophic factors were measured with an ELISA kit. In both intervention groups, there was an improvement in depressive symptoms significantly between baseline and post-intervention. In the combined intervention, GDNF serum levels increased significantly from baseline to post-intervention. However, there were no differences in BDNF and NGF serum levels. In the usual treatment group, no changes were observed in serum levels of GDNF, BDNF, and NGF the post-intervention in individuals. Our data suggests that only combined intervention was effective in improving depressive symptoms and increasing GDNF levels in a sample of young adults with bipolar disorder.
Assuntos
Transtorno Bipolar/sangue , Transtorno Bipolar/terapia , Fator Neurotrófico Derivado do Encéfalo/sangue , Fator de Crescimento Neural/sangue , Avaliação de Processos e Resultados em Cuidados de Saúde , Educação de Pacientes como Assunto/métodos , Psicoterapia Breve/métodos , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto JovemRESUMO
Plasma lipids have been extensively studied in sedentary and in subjects practicing exercise training, but not in extreme inactivity as occurs in bedridden patients. This is important for the care of bedridden patients and understanding the overall plasma lipid regulation. Here, we investigated plasma lipids, lipid transfers to HDL and inflammatory markers in bedridden patients. Fasting blood samples were collected from 23 clinically stable bedridden patients under long-term care (>90 days) and 26 normolipidemic sedentary subjects, paired for age and gender. In vitro transfer of four lipids to HDL was performed by incubating plasma with donor nanoparticles containing radioactive lipids. Total (193 ± 36 vs 160 ± 43, p = 0.005), LDL (124 ± 3 vs 96 ± 33 p = 0.003) and HDL-cholesterol (45 ± 10 vs 36 ± 13, p = 0.008), apolipoprotein A-I (134 ± 20 vs 111 ± 24, p = 0.001) and oxidized LDL (53 ± 13 vs 43 ± 12, p = 0.011) were lower in bedridden patients, whereas triglycerides, apolipoprotein B, CETP and LCAT were equal in both groups. Transfers of all lipids, namely unesterified cholesterol, cholesterol esters, triglycerides and phospholipids, to HDL were lower in bedridden patients, probably due to their lower HDL-cholesterol levels. Concentrations of IL-1ß, IL-6, IL-8, HGF and NGF were higher in bedridden patients compared to sedentary subjects. In conclusion, inactivity had great impact on HDL, by lowering HDL-cholesterol, apolipoprotein A-I and thereby cholesterol transfers to the lipoprotein, which suggests that inactivity may deteriorate HDL protection beyond the ordinary sedentary condition.
Assuntos
Apolipoproteína A-I/análise , Biomarcadores/sangue , HDL-Colesterol/sangue , Inflamação/metabolismo , Lipoproteínas LDL/análise , Adulto , Apolipoproteína A-I/sangue , Pessoas Acamadas , Ésteres do Colesterol , Feminino , Fator de Crescimento de Hepatócito/sangue , Humanos , Interleucina-6/sangue , Interleucina-8/sangue , Lipídeos/sangue , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Fator de Crescimento Neural/sangue , Comportamento SedentárioRESUMO
Abstract Toxoplasmic retinochoroiditis (TR) is the most common identifiable cause of posterior uveitis in Brazil. Response to treatment and clinical presentation may vary significantly. We assessed serum levels of brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), neurotrophin (NT)-3, and NT-4/5 in patients with active TR, before and after TR treatment. Methods: Twenty patients with active lesion and 15 healthy controls were enrolled in the study. Serum concentration of neurotrophic factors was determined by enzyme-linked immunosorbent assay. Results: BDNF levels were significantly higher in patients before treatment when compared with controls (p = 0.0015). There was no significant difference in pro-BDNF, NGF, GDNF, NT-3, and NT-4/5 levels between TR patients and controls. Treatment did not affect the levels of these factors. Conclusion: BDNF may be released in the context of the active TR inflammatory response.
Assuntos
Humanos , Masculino , Feminino , Adulto , Biomarcadores/sangue , Toxoplasmose Ocular/sangue , Coriorretinite/sangue , Ensaio de Imunoadsorção Enzimática , Estudos de Casos e Controles , Coriorretinite/parasitologia , Fator Neurotrófico Derivado do Encéfalo/sangue , Fator de Crescimento Neural/sangue , Neurotrofina 3/sangue , Fator Neurotrófico Derivado de Linhagem de Célula Glial/sangue , Fatores de Crescimento Neural/sangueRESUMO
Toxoplasmic retinochoroiditis (TR) is the most common identifiable cause of posterior uveitis in Brazil. Response to treatment and clinical presentation may vary significantly. We assessed serum levels of brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), neurotrophin (NT)-3, and NT-4/5 in patients with active TR, before and after TR treatment. METHODS: Twenty patients with active lesion and 15 healthy controls were enrolled in the study. Serum concentration of neurotrophic factors was determined by enzyme-linked immunosorbent assay. RESULTS: BDNF levels were significantly higher in patients before treatment when compared with controls (p=0.0015). There was no significant difference in pro-BDNF, NGF, GDNF, NT-3, and NT-4/5 levels between TR patients and controls. Treatment did not affect the levels of these factors. CONCLUSION: BDNF may be released in the context of the active TR inflammatory response.
Assuntos
Biomarcadores/sangue , Coriorretinite/sangue , Toxoplasmose Ocular/sangue , Adulto , Fator Neurotrófico Derivado do Encéfalo/sangue , Estudos de Casos e Controles , Coriorretinite/parasitologia , Ensaio de Imunoadsorção Enzimática , Feminino , Fator Neurotrófico Derivado de Linhagem de Célula Glial/sangue , Humanos , Masculino , Fator de Crescimento Neural/sangue , Fatores de Crescimento Neural/sangue , Neurotrofina 3/sangueRESUMO
OBJECTIVE: The aim of this study was to determine the role of nerve growth factor (NGF) in the first-trimester screening for preeclampsia (PE). METHODS: Uterine artery Doppler (UtAD) was determined transvaginally. Maternal concentrations of NGF were assessed in 42 patients who subsequently developed PE and in 95 controls. Quantile and multivariate regression analyses were performed for the NGF and UtAD adjustment and expressed as the multiple of the median (MoM) of the unaffected group. Logistic regression analysis was conducted to identify the best model for the prediction of PE. RESULTS: The maternal plasma concentration of NGF exhibited a trend towards lower values in patients who subsequently developed early-onset PE (e-PE) compared to controls (10.7 vs. 38.2 pg/ml, respectively; p = not significant). The median MoM NGF in the all-PE, e-PE and control groups was 0.97 (95% CI 0.13-3.36), 0.62 (95% CI 0.16-2.19) and 1.00 (95% CI 0.20-2.94), respectively (p = not significant). The best predictors of PE were previous PE, chronic hypertension and UtAD. With a false-positive rate of 10%, the detection rates (DRs) of all-PE and e-PE were 38 and 50%, respectively. The addition of MoM NGF did not improve the DR of PE. CONCLUSION: First-trimester NGF tends to be lower in patients who subsequently develop e-PE.
Assuntos
Fator de Crescimento Neural/sangue , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/diagnóstico por imagem , Primeiro Trimestre da Gravidez/sangue , Ultrassonografia Doppler em Cores , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Neovascularização Patológica/sangue , Neovascularização Patológica/diagnóstico por imagem , Projetos Piloto , Fator de Crescimento Placentário/sangue , Gravidez , Estudos Retrospectivos , Ultrassonografia Doppler em Cores/métodosRESUMO
Nerve growth factor (NGF) is an important member of the neurotrophins group and their involvement in the pathophysiology of major depression disorder (MDD) and suicide risk (SR) has been recently suggested. The aim of this study is to evaluate the changes in NGF serum levels in individuals with MDD and with or without risk of suicide, in subjects from a young population-based sample. This is a paired cross-sectional study nested in a population-based study. Individuals were rated for MDD and SR by a diagnostic interview--Mini International Neuropsychiatric Interview (M.I.N.I). The total population of the sample was comprised of 141 subjects distributed in three groups: 47 healthy controls, 47 subjects with current depressive episode without SR (MDD) and 47 subjects with current depressive episode and with SR (MDD + SR). NGF serum levels were significantly reduced in the MDD and MDD + SR groups when compared with controls (p ≤ 0.001). However, there were no differences in NGF levels between the MDD and MDD + SR groups (p = 1.000). These results suggest that reduced NGF serum levels can be a possible biomarker of MDD.
Assuntos
Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/psicologia , Fator de Crescimento Neural/sangue , Suicídio/psicologia , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Masculino , Risco , Adulto JovemRESUMO
BACKGROUND: There is evidence of decreased neurotrophic support in Alzheimer's disease (AD), including its prodromal stages, but it is not clear whether this abnormality represents a marker of this process. OBJECTIVE: To determine serum concentrations of a panel of neurotrophic factors (BDNF, NGF, and GDNF) in a cross-section of elderly patients with mild cognitive impairment (MCI) and AD compared to cognitively healthy controls, and to evaluate whether abnormal levels of these factors at baseline predict the transition from MCI to dementia. METHODS: A total of 134 older adults were enrolled in this study. Twenty-six patients with mild to moderate AD, 62 with MCI, and 46 cognitively healthy older adults (controls) were subjected to a clinical evaluation including several cognitive tests. Peripheral blood was drawn and serum levels of BDNF, NGF, and GDNF were measured by enzyme-linked immunosorbent assay. APOE genotyping was performed by PCR assays. RESULTS: Serum concentrations of BDNF, NGF, and GDNF were significantly reduced in cognitively impaired subjects (i.e., MCI and AD) as compared to controls, although only the former two remained statistically different after controlling for age, gender, and cognitive performance (pâ=â0.05 and pâ=â0.01, respectively). Lower BDNF and NGF levels were also observed in the sub-sample of MCI patients who progressed to dementia upon follow-up (pâ=â0.02 and pâ=â0.002, respectively). CONCLUSION: Abnormalities in neurotrophic systems are observed at early stages of AD and may represent a marker of cognitive deterioration.
Assuntos
Doença de Alzheimer/sangue , Biomarcadores/sangue , Disfunção Cognitiva/sangue , Idoso , Idoso de 80 Anos ou mais , Apolipoproteínas E/genética , Fator Neurotrófico Derivado do Encéfalo/sangue , Estudos de Casos e Controles , Cognição , Progressão da Doença , Feminino , Genótipo , Fator Neurotrófico Derivado de Linhagem de Célula Glial/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fator de Crescimento Neural/sangue , Testes NeuropsicológicosRESUMO
BACKGROUND: The diagnosis of alcohol use disorder is based on clinical signs and on the measurement of biological markers. However, these markers are neither sufficiently sensitive, nor specific enough, for determining the effects of alcohol abuse on the central nervous system. Serum neurotrophins are important regulators of neural survival, development, function, and plasticity and have been found to be reduced in alcohol use disorder. The aim of this study was to investigate the alterations in serum neurotrophin levels (brain-derived neurotrophic factor [BDNF], glial-derived neurotrophic factor [GDNF], and nerve growth factor [NGF]) in alcohol use disorder in a young population, and thus possibly representing the early stages of the illness. METHODS: This is a cross-sectional study, nested in a population-based study of people aged 18 to 35, involving 795 participants. The participants responded to the CAGE questionnaire, and a CAGE score of ≥2 was considered to be a positive screen for the abuse/dependence or moderate to severe alcohol use disorder. Serum BDNF, GDNF, and NGF levels were measured by ELISA. RESULTS: In the CAGE ≥ 2 group, GDNF (p ≤ 0.001) and NGF (p ≤ 0.001) serum levels were significantly increased, and the BDNF elevation was near a statistical significance (p = 0.068) when compared to the CAGE < 2 group. A significantly positive correlation was observed only in the CAGE ≥ 2 group for BDNF/GDNF (r = 0.37, p < 0.001) and GDNF/NGF (r = 0.84, p < 0.001) levels. The correlation between the NGF and BDNF levels was significantly positive in both groups (r = 0.28, p < 0.001 for the CAGE < 2 group, and r = 0.30, p = 0.008 for the CAGE ≥ 2 group). CONCLUSIONS: These results suggest that elevated neurotrophins are candidate markers for the early stages of alcohol misuse.
Assuntos
Alcoolismo/sangue , Fator Neurotrófico Derivado do Encéfalo/sangue , Fator Neurotrófico Derivado de Linhagem de Célula Glial/sangue , Fator de Crescimento Neural/sangue , Adolescente , Adulto , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Adulto JovemRESUMO
OBJECTIVES: Evaluate the levels of a neurotrophic factor and some neurotrophins in the plasma of patients with Autism Spectrum Disorders (ASD). DESIGN: This study enrolled 30 children with ASD and 19 healthy children. Plasma levels of the neurotrophins BDNF, NGF, NT3, NT4 and of the neurotrophic factor GDNF were measured by Enzyme-Linked Immunosorbent Assay. SETTING: The etiopathogenesis of ASD is largely unknown, but it seems to involve dysfunction in several biological systems. One of these systems comprises the neurotrophic factors, which are molecules involved in many processes in the central nervous system, including neuronal survival, synaptogenesis and synaptic plasticity. Recent studies have shown association between neurotrophic factors and ASD. RESULTS: No differences in plasma BDNF, NGF, NT3, NT4 and GDNF were found between ASD and control. Neurotrophic factors are not altered in ASD. CONCLUSIONS: These molecules may play a minor role in ASD.
Assuntos
Transtornos Globais do Desenvolvimento Infantil/sangue , Transtornos Globais do Desenvolvimento Infantil/epidemiologia , Fatores de Crescimento Neural/sangue , Adolescente , Adulto , Fator Neurotrófico Derivado do Encéfalo/sangue , Criança , Pré-Escolar , Feminino , Fator Neurotrófico Derivado de Linhagem de Célula Glial/sangue , Humanos , Masculino , Idade Materna , Pessoa de Meia-Idade , Fator de Crescimento Neural/sangue , Plasticidade Neuronal/fisiologia , Neurotrofina 3/sangue , Fatores de Risco , Adulto JovemRESUMO
Recent studies have evaluated the role of brain-derived neurotrophic factor (BDNF) in mood disorders; however, little is known about alterations in nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF). The aim of this study was to evaluate differences among serum neurotrophic factors (BDNF, NGF and GDNF) in depressed patients and healthy controls and to verify the association between serum neurotrophic levels and clinical characteristics in a young, depressed population stratified by gender. This is a cross-sectional study with depressed patients and population controls 18-29 years of age. The concentrations of neurotrophic factors were determined by the ELISA method. The diagnosis of depression and the duration of the disease were assessed by the Structured Clinical Interview according to the diagnostic and statistical manual of mental disorders. Depression severity was measured with the 17-item Hamilton Rating Scale for Depression, and the severity of anxiety symptoms was measured using the Hamilton Anxiety Rating Scale. Serum BDNF and GDNF were lower in major depressive disorder (MDD) patients compared to controls (p ≤ 0.001). Serum NGF levels were higher in MDD patients versus controls (p ≤ 0.001). BDNF was associated with the duration of disease only in women (p = 0.005). GDNF was not associated with clinical characteristics in either gender. In women, NGF was associated with the severity of depressive symptoms (p = 0.009), anxiety (p = 0.011) and disease duration (p = 0.005). NGF was associated with disease duration in men (p = 0.026). Our results demonstrated that significant neurochemical differences in NGF and BDNF, but not in GDNF, were associated with the clinical features of MDD when patients were stratified by gender.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/sangue , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/diagnóstico , Fator Neurotrófico Derivado de Linhagem de Célula Glial/sangue , Fator de Crescimento Neural/sangue , Caracteres Sexuais , Adulto , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Fatores de Crescimento Neural/sangue , Adulto JovemRESUMO
BACKGROUND: Early adverse experiences are associated with increased risk of developing psychiatric disorders, although little is known about the neurobiological mediators involved. The mechanisms by which early environmental influences may mediate vulnerability in the development of offspring await further investigation. The present study correlated the NGF, BDNF, IL-6 and cortisol levels of mothers with postpartum affective disorders (PPAD) with infant development. METHODS: A longitudinal study was performed with 152 pregnant women and their infants. Between 60 and 120 days after delivery, women were interviewed and provided biological samples for biochemical analysis, and the infants were examined for neurobiological-motor development. RESULTS: Overall, the mothers' history of affective disorders, PPAD and anxiety disorder were associated with infant motor development. Using an adjusted linear regression analysis, PPAD (pâ=â0.049), maternal anxiety disorder (pâ=â0.043), NGF level (pâ=â0.034) and infant cortisol level (pâ=â0.013) were associated with infant motor development. Using a factorial analysis of primary components, two components were retained. The psychological factor was characterized by a positive loading of a history of affective disorder, PPAD and anxiety disorder. For the biological factor, infant cortisol adhered negatively with infant motor development, but NGF was positively associated. The psychological factor had a negative association, but the biological factor had a positive association with infant motor development. CONCLUSIONS: There are few studies that have focused on the relationship of biomarkers and infant neurodevelopment. Our study points that psychological and biological factors are associated with infant motor development, however the causal relationship between these factors is still to be defined.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/sangue , Interleucina-6/sangue , Transtornos do Humor/sangue , Fator de Crescimento Neural/sangue , Adulto , Transtornos de Ansiedade/sangue , Transtornos de Ansiedade/fisiopatologia , Feminino , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Transtornos Mentais/sangue , Transtornos Mentais/fisiopatologia , Transtornos do Humor/fisiopatologia , Mães/psicologia , Destreza Motora , Período Pós-Parto , Gravidez , Complicações na Gravidez , Análise de Componente Principal , Transtornos Puerperais/sangue , Transtornos Puerperais/fisiopatologiaRESUMO
In humans, exposure to organic solvents (OS) is frequent in work activities or as a recreational inhalant, inducing severe neuropathy (secondary to demyelization of peripheral nerves). We have previously shown that all-trans retinoic acid (ATRA) increases local content of neural growth factor (NGF), improving peripheral neuropathy of diverse origins. In this study, we evaluated the effect of ATRA on OS-induced peripheral neuropathy in experimental mice. Two simultaneous experiments were performed. The first one aimed to evaluate ATRA for the prevention of damage induced by OS, the second to test ATRA as an OS-induced neuropathy treatment. Nociceptive threshold latency and NGF concentration in serum and in peripheral nerves were determined. Morphological changes and evidence of sciatic nerve regeneration were evaluated. Mice exposed to OS developed neuropathy and axonal degeneration. ATRA diminished the effects of OS inhalation on sensorial changes and nerve morphology. Treatment with ATRA reversed sensorial and nerve morphological changes of OS-induced neuropathy, and this was associated with increased contents of NGF. Similar to previous experiences on diabetic and toxic neuropathy, ATRA reduced and partially reversed the peripheral neuropathy caused by OS exposure. These favorable effects apparently are due to local production of NGF induced by neural regeneration in response to the administration of retinoic acid.
Assuntos
Regeneração Nervosa/efeitos dos fármacos , Limiar da Dor/efeitos dos fármacos , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Tretinoína/uso terapêutico , Animais , Camundongos , Fator de Crescimento Neural/sangue , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/metabolismo , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/lesões , Nervo Isquiático/metabolismo , Solventes , Tretinoína/farmacologiaRESUMO
BACKGROUND: Neurotrophic factors have been investigated in the pathophysiology of alcohol and drug dependence and have been related to early life stress driving developmental programming of neuroendocrine systems. METHODS: We conducted a follow-up study that aimed to assess the plasma levels of glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT3) and neurotrophin-4/5 (NT4/5) in crack users during 3 weeks of early abstinence in comparison with healthy controls. We performed a comprehensive clinical assessment in female inpatients with crack cocaine dependence (separated into 2 groups: participants with (CSA+) and without (CSA-) a history of childhood sexual abuse) and a group of nonuser control participants. RESULTS: Our sample included 104 women with crack cocaine dependence and 22 controls; of the women who used crack cocaine, 22 had a history of childhood sexual abuse and 82 did not. The GDNF plasma levels in the CSA+ group increased dramatically during 3 weeks of detoxification. In contrast, those in the CSA- group showed lower and stable levels of GDNF under the same conditions. Compared with the control group, BDNF plasma levels remained elevated and NGF levels were reduced during early abstinence. We found no differences in NT3 and NT4/5 between the patients and controls. However, within-group analyses showed that the CSA+ group exhibited higher levels of NT4/5 than the CSA- group at the end of detoxification. LIMITATIONS: Some of the participants were using neuroleptics, mood stabilizers or antidepressants; our sample included only women; memory bias could not be controlled; and we did not investigate the possible confounding effects of other forms of stress during childhood. CONCLUSION: This study supports the association between early life stress and peripheral neurotrophic factor levels in crack cocaine users. During early abstinence, plasmastic GDNF and NT4/5 were the only factors to show changes associated with a history of childhood sexual abuse.
Assuntos
Abuso Sexual na Infância , Transtornos Relacionados ao Uso de Cocaína/sangue , Cocaína Crack , Fatores de Crescimento Neural/sangue , Estresse Psicológico/sangue , Adulto , Criança , Feminino , Seguimentos , Fator Neurotrófico Derivado de Linhagem de Célula Glial/sangue , Humanos , Modelos Lineares , Fator de Crescimento Neural/sangue , Neurotrofina 3/sangue , Síndrome de Abstinência a Substâncias/sangue , Fatores de TempoRESUMO
INTRODUCTION: Nerve growth factor (NGF) is one of the most abundant neurotrophic factors in the central nervous system and has been involved in several neuropsychiatric disorders. METHODS: We recruited 77 age- and gender-matched elderly subjects (38 with late-life depression, 17 with previous major depressive episode, and 22 healthy subjects in the comparison group). Serum concentration of NGF was determined by enzyme-linked immunosorbent assay. RESULTS: NGF levels were significantly reduced in the depressed patients (p = 0.002) as compared with healthy elderly controls. Elderly control subjects with previous depressive episode also showed a significant reduction in NGF levels as compared with controls (p <0.01); NGF levels were similar between patients with current depressive episode and previous depressive episode (p = 0.2). CONCLUSION: The present findings provide additional evidence to the relevance of reduced neurotrophic support in the pathophysiology of late-life depression. Also, reduced serum NGF level may be a state marker of depression in elderly subjects.