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Depression is a mental disorder characterised by persistent low mood, anhedonia and cognitive impairment that affects an estimated 3.8% of the world's population, including 5% of adults. Peganum harmala L. (P. harmala) is a medicinal plant and has been reported to be effective against Alzheimer's disease, Parkinson's disease and depression. The present study was aimed to evaluate the behavioral and pharmacological effects of P. harmala seed extract in rats exposed to chronic unpredictable mild stress (CUMS) in vivo and to investigate the mechanism of action. CUMS-exposed rats were treated with P. harmala extract (75 and 150 mg/kg, i.p.) for 2 weeks. HPLC analysis was used to determine the concentration of harmaline and harmine alkaloids in the extract. Heavy metal analysis in seeds was performed by ICP-MS. Our results showed that P. harmala at the dose of 150 mg/kg significantly reduced the depressive-like behaviors in CUMS-exposed rats, as evidenced by increased sucrose consumption in the sucrose preference test (SPT), decreased immobility time in the forced swim test (FST) and plasma corticosterone levels, increased the time spent in open arms in the elevated plus maze (EPM), and improved memory and learning in the passive avoidance test (PAT). In addition, P. harmala decreased monoamine oxidase-A (MAO-A) levels, and increased serotonin (5-HT), dopamine (DA), and noradrenaline (NA) levels in the brains of rats exposed to CUMS. P. harmala decreased the expression of the pro-inflammatory transcription factor nuclear factor-κB (NF-κB), and increased the antioxidant nuclear factor erythroid 2-related factor 2 (Nrf2) in rat brain. Furthermore, P. harmala improved brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) protein expression in rat brain. In conclusion, P. harmala at a dose of 150 mg/kg is more effective in preventing depressive-like behavior in CUMS-exposed rats by improving neurotransmitter levels, reducing oxidative stress, suppressing neuroinflammation and activating the BDNF/TrkB pathway, all of which are important in the pathogenesis of depression.
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Losses in dopamine (DA) functioning may contribute to aging-related decline in cognition. Hippocampal DA is necessary for successful episodic memory formation. Previously, we reported that higher DA D2 receptor (D2DR) availability in hippocampus is beneficial for episodic memory only in older carriers of more advantageous genotypes of well-established plasticity-related genetic variations, the brain-derived neurotrophic factor (BDNF, rs6265) and the kidney and brain expressed protein (KIBRA, rs17070145) polymorphisms. Extending our observations to the longitudinal level, the current data show that individuals with one or no beneficial BDNF and KIBRA genotype (n = 80) decline more in episodic memory across five years, without any contribution of losses in hippocampal D2DR availability to memory decline. Although carriers of two beneficial genotypes (n = 39) did not decline overall in episodic memory, losses of hippocampal D2DR availability were predictive of episodic-memory decline among these individuals. Our findings have implications for interventions targeting DA modulation to enhance episodic memory in aging, which may not benefit all older individuals.
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Factor Neurotrófico Derivado del Encéfalo , Genotipo , Hipocampo , Memoria Episódica , Receptores de Dopamina D2 , Humanos , Receptores de Dopamina D2/genética , Receptores de Dopamina D2/metabolismo , Hipocampo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/genética , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Masculino , Femenino , Anciano , Envejecimiento/fisiología , Envejecimiento/genética , Polimorfismo de Nucleótido Simple , Persona de Mediana Edad , Trastornos de la Memoria/genética , Trastornos de la Memoria/metabolismo , Estudios Longitudinales , Polimorfismo Genético/genética , Pruebas Neuropsicológicas , Anciano de 80 o más Años , Péptidos y Proteínas de Señalización IntracelularRESUMEN
The brain-derived neurotrophic factor (BDNF) involves stress regulation and psychiatric disorders. The Val66Met polymorphism in the BDNF gene has been linked to altered protein function and susceptibility to stress-related conditions. This in silico analysis aimed to predict and analyze the consequences of the Val66Met mutation in the BDNF gene of stressed individuals. Computational techniques, including ab initio, comparative, and I-TASSER modeling, were used to evaluate the functional and stability effects of the Val66Met mutation in BDNF. The accuracy and reliability of the models were validated. Sequence alignment and secondary structure analysis compared amino acid residues and structural components. The phylogenetic analysis assessed the conservation of the mutation site. Functional and stability prediction analyses provided mixed results, suggesting potential effects on protein function and stability. Structural models revealed the importance of BDNF in key biological processes. Sequence alignment analysis showed the conservation of amino acid residues across species. Secondary structure analysis indicated minor differences between the wild-type and mutant forms. Phylogenetic analysis supported the evolutionary conservation of the mutation site. This computational study suggests that the Val66Met mutation in BDNF may have implications for protein stability, structural conformation, and function. Further experimental validation is needed to confirm these findings and elucidate the precise effects of this mutation on stress-related disorders.
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Growing evidence supports the notion that brain-derived neurotrophic factor (BDNF) and lactate are potent modulators of mammalian brain function. The modulatory actions of those biomolecules influence a wide range of neuronal responses, from the shaping of neuronal excitability to the induction and expression of structural and synaptic plasticity. The biological actions of BDNF and lactate are mediated by their cognate receptors and specific transporters located in the neuronal membrane. Canonical functions of BDNF occur via the tropomyosin-related kinase B receptor (TrkB), whereas lactate acts via monocarboxylate transporters or the hydroxycarboxylic acid receptor 1 (HCAR1). Both receptors are highly expressed in the central nervous system, and some of their physiological actions are particularly well characterized in the hippocampus, a brain structure involved in the neurophysiology of learning and memory. The multifarious neuronal circuitry between the axons of the dentate gyrus granule cells, mossy fibers (MF), and pyramidal neurons of area CA3 is of great interest given its role in specific mnemonic processes and involvement in a growing number of brain disorders. Whereas the modulation exerted by BDNF via TrkB has been extensively studied, the influence of lactate via HCAR1 on the properties of the MF-CA3 circuit is an emerging field. In this review, we discuss the role of both systems in the modulation of brain physiology, with emphasis on the hippocampal CA3 network. We complement this review with original data that suggest cross-modulation is exerted by these two independent neuromodulatory systems.
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Factor Neurotrófico Derivado del Encéfalo , Fibras Musgosas del Hipocampo , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Fibras Musgosas del Hipocampo/metabolismo , Ácido Láctico/metabolismo , Hipocampo/metabolismo , Células Piramidales/metabolismo , Proteínas Portadoras/metabolismo , Región CA3 Hipocampal/metabolismo , Mamíferos/metabolismoRESUMEN
INTRODUCTION: Depression is frequent among older adults and is a risk factor for dementia. Identifying molecular links between depression and dementia is necessary to shed light on shared disease mechanisms. Reduced brain-derived neurotrophic factor (BDNF) and neuroinflammation are implicated in the pathophysiology of depression and dementia. The exercise-induced hormone, irisin, increases BDNF and improves cognition in animal models of Alzheimer's disease. Lipoxin A4 is a lipid mediator with anti-inflammatory activity. However, the roles of irisin and lipoxin A4 in depression remain to be determined. METHODS: In the present study, blood and CSF were collected from 61 elderly subjects, including individuals with and without cognitive impairment. Screening for symptoms of depression was performed using the 15-item Geriatric Depression Scale (GDS-15). RESULTS: CSF irisin and lipoxin A4 were positively correlated and reduced, along with a trend of BDNF reduction, in elderly individuals with depression, similar to previous observations in patients with dementia. DISCUSSION: Our findings provide novel insight into shared molecular signatures connecting depression and dementia.
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Enfermedad de Alzheimer , Lipoxinas , Animales , Depresión/psicología , Factor Neurotrófico Derivado del Encéfalo , Fibronectinas , BrasilRESUMEN
Abstract Background: Brain Derived Neurotrophic Factor (BDNF) serum levels change with age, physical exercise, and neuropsychiatric disorders such as dementia, depression, anxiety, schizophrenia, and bipolar disorder. Military personnel are physically and mental training with an increased risk of developing mental disorders. Objective: The main objective of this study was determinate the BDNF serum levels in four military samples. 132 participants, administrative personnel (control) and three different Special Operations Forces (SOF) groups participated in the study. Methods: A first group of SOFS was on a training course (SOF-TC), second group exposed to 48 hours of operational stress (SOF-48hS) and third group exposed to two-weeks of operational stress (SOF-2wS). The mini interview was conducted and CAPS, and BNF levels were determined by ELISA assays. Results: Differences in age, were evaluated by ANOVA post-hoc Tukey´s. Differences in BNDF levels are evaluated by the Kruskal-Wallis test post hoc Dunn's. Spearman's correlation was used to analyze the relationship between BDNF and age. The SOF-TC had a BDNF elevation in comparison with Control group that could be related to age differences or the physical and mental training.SOF-2wS had decreased BDNF levels in comparison to the other groups that could be related to the psychosocial stress or other mental disorders such as PTSD. That group, 2 participants showed signs of PTSD. Conclusion: BDNF levels are an accurate method for the evaluation of mental health to prevent, diagnose & treat mental disorders in military personnel exposed to operational stress.
Resumen Introducción: Los niveles séricos del factor neurotrófico derivado del cerebro (BDNF) cambian con la edad, el ejercicio físico y los trastornos neuropsiquiátricos como la demencia, la depresión, la ansiedad, la esquizofrenia y el trastorno bipolar. El personal militar está en formación física y mental con un mayor riesgo de desarrollar trastornos mentales. Objetivo: El objetivo principal de este estudio fue determinar los niveles séricos de BDNF en cuatro muestras militares. Participaron en el estudio 132 individuos entre personal administrativo (control) y tres grupos diferentes de Fuerzas de Operaciones Especiales (SOF). Métodos: Un primer grupo de SOFS estaba en un curso de capacitación (SOF-TC), el segundo grupo expuesto a 48 horas de estrés operativo (SOF-48hS) y el tercer grupo expuesto a dos semanas de estrés operativo (SOF-2wS). Se realizó la minientrevista y se determinaron los niveles de CAPS y BNF mediante ensayos ELISA. Resultados: Las diferencias en edad, se evaluaron mediante ANOVA post hoc de Tukey. Las diferencias en los niveles de BNDF se evalúan mediante la prueba de Dunn post hoc de Kruskal-Wallis. Se utilizó la correlación de Spearman para analizar la relación entre BDNF y la edad. El SOF-TC tuvo una elevación de BDNF en comparación con el grupo control que podría estar relacionado con las diferencias de edad o el entrenamiento físico y mental, tal como PTSD. En ese grupo, dos participantes mostraron signos de PTSD. Conclusión: Los niveles de BDNF son un método preciso para la evaluación de la salud mental para prevenir, diagnosticar y tratar los trastornos mentales en el personal militar expuesto al estrés operativo.
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AIMS: In this study, the effect of intracerebral ventricle injection with a miR-124-3p agomir or antagomir on prognosis and on subventricular zone (SVZ) neural stem cells (NSCs) in adult rats with moderate traumatic brain injury (TBI) was investigated. METHODS: Model rats with moderate controlled cortical impact (CCI) were established and verified as described previously. The dynamic changes in miR-124-3p and the status of NSCs in the SVZ were analyzed. To evaluate the effect of lateral ventricle injection with miR-124-3p analogs and inhibitors after TBI, modified neurological severity scores (mNSSs) and rotarod tests were used to assess motor function prognosis. The variation in SVZ NSC marker expression was also explored. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of predicted miR-124-3p targets was performed to infer miR-124-3p functions, and miR-124-3p effects on pivotal predicted targets were further explored. RESULTS: Administration of miR-124 inhibitors enhanced SVZ NSC proliferation and improved the motor function of TBI rats. Functional analysis of miR-124 targets revealed high correlations between miR-124 and neurotrophin signaling pathways, especially the TrkB downstream pathway. PI3K, Akt3, and Ras were found to be crucial miR-124 targets and to be involved in most predicted functional pathways. Interference with miR-124 expression in the lateral ventricle affected the PI3K/Akt3 and Ras pathways in the SVZ, and miR-124 inhibitors intensified the potency of brain-derived neurotrophic factor (BDNF) in SVZ NSC proliferation after TBI. CONCLUSION: Disrupting miR-124 expression through lateral ventricle injection has beneficial effects on neuroregeneration and TBI prognosis. Moreover, the combined use of BDNF and miR-124 inhibitors might lead to better outcomes in TBI than BDNF treatment alone.
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Lesiones Traumáticas del Encéfalo , Factor Neurotrófico Derivado del Encéfalo , MicroARNs , Células-Madre Neurales , Animales , Lesiones Traumáticas del Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Regulación hacia Abajo , Ventrículos Laterales/metabolismo , MicroARNs/metabolismo , Células-Madre Neurales/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
The objective of this study is to determine whether cannabis influences BDNF levels in patients with psychosis (FEP) and healthy volunteers (HV) to help understand the role of BDNF in psychosis. We assessed the association between BDNF and cannabis in a cohort of FEP antipsychotic-naïve patients and HV, whilst controlling for other potential confounding factors. 70 FEP drug-naive patients and 57 HV were recruited. A sociodemographic variable collection, structured clinical interview, weight and height measurement, substance use determination, and blood collection to determine BDNF levels by ELISA analysis were done. In FEP patients, cannabis use was associated with BDNF levels (high cannabis use was associated with lower BDNF levels). Moreover, cannabis use was statistically significantly associated with age (high use of cannabis was associated with younger age). In HV, no relationship between cannabis use and BDNF levels was observed. Otherwise, cannabis use was significantly associated with tobacco use, so that high cannabis users were also high tobacco users. This study showed a different association between cannabis use and BDNF levels in FEP patients compared with HV, particularly, with high doses of cannabis. These findings may help understand the deleterious effects of cannabis in some vulnerable individuals, as well as discrepancies in the literature.
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Factor Neurotrófico Derivado del Encéfalo/sangre , Uso de la Marihuana/sangre , Trastornos Psicóticos/sangre , Adulto , Factores de Edad , Estudios de Cohortes , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
BACKGROUND: Neurotrophins such as brain-derived neurotrophic factor (BDNF), inflammation and oxidative damage may contribute to the pathophysiology of bipolar disorder (BD) in terms of illness activity. To date, there is a lack of studies linking the cognitive impairment observed in BD with these neurobiological mechanisms. This study aimed to investigate the role of these neurobiological factors in clinical and cognitive outcomes in a sample of bipolar individuals. METHODS: We measured serum BDNF, cytokines and oxidative stress markers in a sample of 133 individuals: 52 euthymic bipolar patients, 32 manic patients and 49 healthy controls. They were all assessed with a comprehensive cognitive battery. Sociodemographic and clinical data were collected. Multiple linear regression models were built to study associations of neurotrophins and inflammatory and oxidative measures with cognitive functioning. RESULTS: BDNF levels were decreased in euthymic (p = 0.039) and manic (p < 0.001) individuals. Conversely, inflammatory (interleukin 6 (IL-6)) (p = 0.019) and oxidative stress (p = 0.003) measures were increased in bipolar individuals compared to controls. BDNF levels were associated with executive functioning (ß = 0.01, p = 0.02) and verbal memory (ß = 0.013, p = 0.005), together with other demographic variables. In particular, verbal memory was also associated with obesity (ß=-0.04, p = 0.005). Neither inflammatory markers, oxidative stress markers nor other relevant clinical variables showed any association with cognitive outcome. CONCLUSIONS: Of all the peripheral neurobiological factors analysed, BDNF was the only one significantly associated with cognitive dysfunction in bipolar disorder individuals. This study emphasizes the role of BDNF not only across mood phases but also in cognitive functioning.
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Trastorno Bipolar , Factor Neurotrófico Derivado del Encéfalo/sangre , Cognición/fisiología , Función Ejecutiva/fisiología , Adulto , Biomarcadores/sangre , Trastorno Bipolar/diagnóstico , Trastorno Bipolar/metabolismo , Trastorno Bipolar/psicología , Correlación de Datos , Femenino , Humanos , Inflamación/sangre , Interleucina-6/sangre , Masculino , Neurobiología/métodos , Pruebas Neuropsicológicas , Estrés Oxidativo/fisiologíaRESUMEN
Background: There is limited evidence concerning the effect of intramuscular electrical stimulation (EIMS) on the neural mechanisms of pain and disability associated with chronic Myofascial Pain Syndrome (MPS). Objectives: To provide new insights into the EIMS long-term effect on pain and disability related to chronic MPS (primary outcomes). To assess if the neuroplasticity state at baseline could predict the long-term impact of EIMS on disability due to MPS we examined the relationship between the serum brain-derived-neurotrophic-factor (BDNF) and by motor evoked potential (MEP). Also, we evaluated if the EIMS could improve the descending pain modulatory system (DPMS) and the cortical excitability measured by transcranial magnetic stimulation (TMS) parameters. Methods: We included 24 right-handed female with chronic MPS, 19-65 years old. They were randomically allocated to receive ten sessions of EIMS, 2 Hz at the cervical paraspinal region or a sham intervention (n = 12). Results: A mixed model analysis of variance revealed that EIMS decreased daily pain scores by -73.02% [95% confidence interval (CI) = -95.28 to -52.30] and disability due to pain -43.19 (95%CI, -57.23 to -29.39) at 3 months of follow up. The relative risk for using analgesics was 2.95 (95% CI, 1.36 to 6.30) in the sham group. In the EIMS and sham, the change on the Numerical Pain Scale (NPS0-10) throughout CPM-task was -2.04 (0.79) vs. -0.94 (1.18), respectively, (P = 0.01). EIMS reduced the MEP -28.79 (-53.44 to -4.15), while improved DPMS and intracortical inhibition. The MEP amplitude before treatment [(Beta = -0.61, (-0.58 to -0.26)] and a more significant change from pre- to post-treatment on serum BDNF) (Beta = 0.67; CI95% = 0.07 to 1.26) were predictors to EIMS effect on pain and disability due to pain. Conclusion: These findings suggest that a bottom-up effect induced by the EIMS reduced the analgesic use, improved pain, and disability due to chronic MPS. This effect might be mediated by an enhancing of corticospinal inhibition as seen by an increase in IC and a decrease in MEP amplitude. Likewise, the MEP amplitude before treatment and the changes induced by the EIMS in the serum BDNF predicted it's long-term clinical impact on pain and disability due MPS. The trial is recorded in ClinicalTrials.gov: NCT02381171.
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BACKGROUND: Aging is one of the most important inevitable risk factors of Alzheimer disease (AD). Oxidative stress plays a critical role in the process of aging. Curcumin has been proposed to improve neural damage, especially neurodegenerative injury, through its antioxidant and anti-inflammatory properties. Therefore, we investigated the effects of curcumin on acrolein-induced AD-like pathologies in HT22 cells. METHODS: HT22 murine hippocampal neuronal cells were treated with 25µM acrolein for 24h with or without pre-treating with curcumin at the selected optimum concentration (5µg/mL) for 30min. Cell viability and apoptosis were measured by CCK8 assay and flow cytometric analysis. Levels of glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) were detected by a GSH assay kit or commercial assay kits, respectively. Alterations in the expression of BDNF/TrkB and key enzymes involved in amyloid precursor protein (APP) metabolism were assessed by western blotting. RESULTS: Data showed that curcumin significantly reversed acrolein-induced oxidative stress indicated by depletion of GSH and SOD, and elevation of MDA. The findings also suggested curcumin's potential in protecting HT22 cells against acrolein through regulating the BDNF/TrkB signaling. In addition, acrolein-induced reduction in A-disintegrin and metalloprotease, and the increase of amyloid precursor protein, ß-secretase, and receptor for advanced glycation end products were reversed either, and most of them were nearly restored to the control levels by curcumin. CONCLUSION: These findings demonstrate the protective effects of curcumin on acrolein-induced neurotoxicity in vitro, which further suggests its potential role in the treatment of AD.
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Acroleína/antagonistas & inhibidores , Acroleína/toxicidad , Curcumina/farmacología , Hipocampo/citología , Fármacos Neuroprotectores/farmacología , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/biosíntesis , Animales , Apoptosis/efectos de los fármacos , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Desintegrinas/metabolismo , Glutatión/metabolismo , Malondialdehído/metabolismo , Glicoproteínas de Membrana/metabolismo , Metaloproteasas/metabolismo , Ratones , Proteínas Tirosina Quinasas/metabolismo , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
Neurotrophic factors regulate survival and growth of neurons. The urinary bladder is innervated via both sympathetic and parasympathetic neurons located in the major pelvic ganglion. The aim of the present study was to characterize the effects of the neurotrophins nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3) on the sprouting rate of sympathetic and parasympathetic neurites from the female mouse ganglion. The pelvic ganglion was dissected out and attached to a petri dish and cultured in vitro. All three factors (BDNF, NT-3 and NGF) stimulated neurite outgrowth of both sympathetic and parasympathetic neurites although BDNF and NT-3 had a higher stimulatory effect on parasympathetic ganglion cells. The neurotrophin receptors TrkA, TrkB and TrkC were all expressed in neurons of the ganglia. Co-culture of ganglia with urinary bladder tissue, but not diaphragm tissue, increased the sprouting rate of neurites. Active forms of BDNF and NT-3 were detected in urinary bladder tissue using western blotting whereas tissue from the diaphragm expressed NGF. Neurite outgrowth from the pelvic ganglion was inhibited by a TrkB receptor antagonist. We therefore suggest that the urinary bladder releases trophic factors, including BDNF and NT-3, which regulate neurite outgrowth via activation of neuronal Trk-receptors. These findings could influence future strategies for developing pharmaceuticals to improve re-innervation due to bladder pathologies.
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Factor Neurotrófico Derivado del Encéfalo/metabolismo , Ganglios Autónomos/metabolismo , Factor de Crecimiento Nervioso/metabolismo , Proyección Neuronal/fisiología , Neurotrofina 3/metabolismo , Vejiga Urinaria/inervación , Animales , Factor Neurotrófico Derivado del Encéfalo/administración & dosificación , Células Cultivadas , Técnicas de Cocultivo , Diafragma/inervación , Femenino , Ganglios Autónomos/citología , Ganglios Autónomos/efectos de los fármacos , Masculino , Ratones , Factor de Crecimiento Nervioso/administración & dosificación , Proyección Neuronal/efectos de los fármacos , Neurotrofina 3/administración & dosificación , Sistema Nervioso Parasimpático/citología , Sistema Nervioso Parasimpático/efectos de los fármacos , Sistema Nervioso Parasimpático/metabolismo , Pelvis , Próstata/inervación , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores , Proteínas Tirosina Quinasas Receptoras/metabolismo , Sistema Nervioso Simpático/citología , Sistema Nervioso Simpático/efectos de los fármacos , Sistema Nervioso Simpático/metabolismoRESUMEN
While the brain-derived neurotrophic factor (BDNF) gene and its multiple transcripts have been recognized as a key factor for learning, but the specific involvement of BDNF translated from BDNF transcripts with short-3' untranslated region (short 3' UTR) in learning and memory requires further analysis. In this paper, we present data to show that the transduction of hippocampal CA1 neurons with AAV9-5' UTR-BDNF (short 3' UTR)-IRES-ZsGreen and the subsequent expression of BDNF enhanced the phosphorylation of synaptic plasticity relevant proteins and improved passive avoidance and object location, but not object recognition memory. In addition, BDNF improved the relearning of object location. At higher BDNF overexpression levels, the fear behavior was accompanied with a decline in the passive avoidance memory 24h post training, and with an enhanced fear conditioning performance. In addition, these animals developed spontaneous seizures. Thus, the expression of BDNF in the hippocampal CA1 region has the potential to improve fear and object location memory in wild type mouse strains when the region and expression levels of BDNF are well controlled.
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Factor Neurotrófico Derivado del Encéfalo/genética , Región CA1 Hipocampal/metabolismo , Memoria/fisiología , Plasticidad Neuronal/fisiología , Neuronas/metabolismo , Biosíntesis de Proteínas/fisiología , Transducción de Señal/fisiología , Regiones no Traducidas 3' , Animales , Reacción de Prevención/fisiología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Miedo/fisiología , Aprendizaje/fisiología , Ratones , Fosforilación , Sinapsis/metabolismoRESUMEN
Myofascial pain syndrome (MPS) is a leading cause of chronic musculoskeletal pain. However, its neurobiological mechanisms are not entirely elucidated. Given the complex interaction between the networks involved in pain process, our approach, to providing insights into the neural mechanisms of pain, was to investigate the relationship between neurophysiological, neurochemical and clinical outcomes such as corticospinal excitability. Recent evidence has demonstrated that three neural systems are affected in chronic pain: (i) motor corticospinal system; (ii) internal descending pain modulation system; and (iii) the system regulating neuroplasticity. In this cross-sectional study, we aimed to examine the relationship between these three central systems in patients with chronic MPS of whom do/do not respond to the Conditioned Pain Modulation Task (CPM-task). The CPM-task was to immerse her non-dominant hand in cold water (0-1°C) to produce a heterotopic nociceptive stimulus. Corticospinal excitability was the primary outcome; specifically, the motor evoked potential (MEP) and intracortical facilitation (ICF) as assessed by transcranial magnetic stimulation (TMS). Secondary outcomes were the cortical excitability parameters [current silent period (CSP) and short intracortical inhibition (SICI)], serum brain-derived neurotrophic factor (BDNF), heat pain threshold (HPT), and the disability related to pain (DRP). We included 33 women, (18-65 years old). The MANCOVA model using Bonferroni's Multiple Comparison Test revealed that non-responders (n = 10) compared to responders (n = 23) presented increased intracortical facilitation (ICF; mean ± SD) 1.43 (0.3) vs. 1.11 (0.12), greater motor-evoked potential amplitude (µV) 1.93 (0.54) vs. 1.40 (0.27), as well a higher serum BDNF (pg/Ml) 32.56 (9.95) vs. 25.59 (10.24), (P < 0.05 for all). Also, non-responders presented a higher level of DRP and decreased HPT (P < 0.05 for all). These findings suggest that the loss of net descending pain inhibition was associated with an increase in ICF, serum BDNF levels, and DRP. We propose a framework to explain the relationship and potential directionality of these factors. In this framework we hypothesize that increased central sensitization leads to a loss of descending pain inhibition that triggers compensatory mechanisms as shown by increased motor cortical excitability.
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AIMS: To explore the association between plasma concentrations of brain-derived neurotrophic factor (BDNF) and the occurrence of emergence agitation (EA) in the elderly after gastrointestinal surgery. METHODS: Seventy-two patients were recruited, who received gastrointestinal surgery and general anesthesia. BDNF level of blood was detected by ELISA before anesthesia (baseline), 10 min after tracheal intubation before the start of surgery, at skin closure, 10 min after tracheal extubation, and 24 h postoperatively. Patients with a Ricker Sedation-Agitation Scale (RSAS) score ≥5 at any time in the post anesthesia care unit were considered to have emergence agitation. RESULTS: The incidence of EA in this population was 40 % (29/72). The EA group had higher plasma BDNF levels at skin closure (497.86 ± 69.65 vs. 307.86 ± 51.91, p < 0.05) and especially at 10 min after tracheal extubation (900 ± 224.6 vs. 476.28 ± 107.15, p < 0.001). Moreover, the levels of plasma BDNF at skin closure, 10 min after tracheal extubation and postoperative pain, were positively related with RSAS scores. CONCLUSIONS: Our results suggest that plasma BDNF is associated with the occurrence of emergence agitation after gastrointestinal surgery.
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Factor Neurotrófico Derivado del Encéfalo/sangre , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Delirio del Despertar/epidemiología , Anciano , Extubación Traqueal , Periodo de Recuperación de la Anestesia , Anestesia General/efectos adversos , Anestesia General/métodos , Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Dolor Postoperatorio/epidemiología , Agitación Psicomotora/epidemiologíaRESUMEN
Ischemic stroke and ischemia/reperfusion (I/R) injury induced by thrombolytic therapy are conditions with high mortality and serious long-term physical and cognitive disabilities. They have a major impact on global public health. These disorders are associated with multiple insults to the cerebral microcirculation, including reactive oxygen species (ROS) overproduction, leukocyte adhesion and infiltration, brain blood barrier (BBB) disruption, and capillary hypoperfusion, ultimately resulting in tissue edema, hemorrhage, brain injury and delayed neuron damage. Traditional Chinese medicine (TCM) has been used in China, Korea, Japan and other Asian countries for treatment of a wide range of diseases. In China, the usage of compound TCM preparation to treat cerebrovascular diseases dates back to the Han Dynasty. Even thousands of years earlier, the medical formulary recorded many classical prescriptions for treating cerebral I/R-related diseases. This review summarizes current information and underlying mechanisms regarding the ameliorating effects of compound TCM preparation, Chinese materia medica, and active components on I/R-induced cerebral microcirculatory disturbances, brain injury and neuron damage.
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Aging is a normal physiological process accompanied by cognitive decline. This aging process has been the primary risk factor for development of aging-related diseases such as Alzheimer's disease (AD). Cognitive deficit is related to alterations of neurotrophic factors level such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and glial cell-derived neurotrophic factor (GDNF). These strong relationship between aging and AD is important to investigate the time which they overlap, as well as, the pathophysiological mechanism in each event. Considering that aging and AD are related to cognitive impairment, here we discuss the involving these neurotrophic factors in the aging process and AD.
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Alzheimer's disease (AD) is a neurodegenerative disorder with progressive degeneration of the hippocampal and cortical neurons. This study was designed to demonstrate the protective effect of caffeine on gene expression of brain derived neurotrophic factor (BDNF) and its receptor neural receptor protein-tyrosine kinase-ß (TrkB) as well as glial fibrillary acidic protein (GFAP) and Ki-67 immunoreactivity in Aluminum chloride (AlCl3) induced animal model of AD. Fifty adult rats included in this study were classified into 5 group (10 rats each); negative and positive control groups (I&II), AD model group (III), group treated with caffeine from the start of AD induction (IV) and group treated with caffeine two weeks before AD induction (V). Hippocampal tissue BDNF and its receptor (TrkB) gene expression by real time RT-PCR in addition to immunohistochemical study of GFAP and Ki67 immunoreactivity were performed for all rats in the study. The results of this study revealed that caffeine has protective effect through improving the histological and immunohistochemical findings induced by AlCl3 as well as BDNF and its receptor gene expression. It could be concluded from the current study, that chronic caffeine consumption in a dose of 1.5 mg/kg body weight daily has a potentially good protective effect against AD.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Cafeína/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Cloruro de Aluminio , Compuestos de Aluminio/efectos adversos , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/metabolismo , Animales , Factor Neurotrófico Derivado del Encéfalo/genética , Cloruros/efectos adversos , Modelos Animales de Enfermedad , Proteína Ácida Fibrilar de la Glía/genética , Proteína Ácida Fibrilar de la Glía/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/patología , Humanos , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Masculino , Neuronas/efectos de los fármacos , Neuronas/patología , Ratas , Ratas Sprague-Dawley , Proteínas Tirosina Quinasas Receptoras/genética , Proteínas Tirosina Quinasas Receptoras/metabolismoRESUMEN
Although recent studies have found that HO-1 plays an important role in neuronal survival, little is known about the precise mechanisms occurring during cerebral ischemia/reperfusion (I/R). Therefore, the aim of this study was to investigate the neuroprotective mechanisms of HO-1 against ischemic brain injury induced by cerebral I/R and to explore whether the BDNF-TrkB-PI3K/Akt signaling pathway contributed to the protection provided by HO-1. Over-expressed HO-1 plasmids were employed to induce the overexpression of HO-1 through hippocampi CA1 injection 5 days before the cerebral I/R animal model was induced by four-vessel occlusion for 15 min transient ischemia and followed by reperfusion in Sprague-Dawley rats. Immunoblotting was carried out to examine the expression of the related proteins, and HE-staining was used to detect the percentage of living neurons in the hippocampal CA1 region. The results showed that over-expressed HO-1 could significantly protect neurons against cerebral I/R. Furthermore, the protein expression of BDNF, TrkB and p-Akt also increased in the rats treated with over-expressed HO-1 plasmids. However, treatment with tropomyosin receptor kinase B (TrkB) receptor antagonist (K252a) reversed the HO-1-induced increase in BDNF and p-Akt protein levels and decreased the level of cleaved caspase-3 protein in I/R rats. In summary, our results imply that HO-1 can decrease cell apoptosis in the I/R rat brain and that the mechanism may be related to the activation of the BDNF-TrkB-PI3K/Akt signaling pathway.
Asunto(s)
Región CA1 Hipocampal/fisiopatología , Hemo Oxigenasa (Desciclizante)/metabolismo , Neuronas/fisiología , Accidente Cerebrovascular/fisiopatología , Animales , Apoptosis/fisiología , Isquemia Encefálica/patología , Isquemia Encefálica/fisiopatología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Región CA1 Hipocampal/efectos de los fármacos , Región CA1 Hipocampal/patología , Carbazoles/farmacología , Caspasa 3/metabolismo , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/farmacología , Hemo Oxigenasa (Desciclizante)/genética , Alcaloides Indólicos/farmacología , Masculino , Neuronas/efectos de los fármacos , Neuronas/patología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas Sprague-Dawley , Receptor trkB/antagonistas & inhibidores , Receptor trkB/metabolismo , Transducción de Señal/efectos de los fármacos , Accidente Cerebrovascular/patología , TransfecciónRESUMEN
Alzheimer's disease (AD) is a disorder characterized by the accumulation of abnormally folded protein fragments in neurons, i.e., ß-amyloid (Aß) and tau protein, leading to cell death. Several neuropeptides present in the central nervous system (CNS) are believed to be involved in the pathophysiology of AD. Among them, neuropeptide Y (NPY), a small peptide widely distributed throughout the brain, has generated interest because of its role in neuroprotection against excitotoxicity in animal models of AD. In addition, it has been shown that NPY modulates neurogenesis. Interestingly, these latter effects are similar to those elicited by neurotrophins, which are critical molecules for the function and survival of neurons that degenerate during the course of AD. In this review we summarize the evidence for the involvement of NPY and neurotrophins in AD pathogenesis, and the similarity between them in CNS neurons. Finally, we recapitulate our recent in-vitro evidence for the involvement of neurotrophin nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in the neuroprotective effect elicited by NPY in AD neuron-like models (neuroblastoma cells or primary cultures exposed to toxic concentrations of Aß's pathogenic fragment 25-35), and propose a putative mechanism based on NPY-induced inhibition of voltage-dependent Ca(2+) influx in pre- and post-synaptic neurons.