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Post-traumatic stress disorder (PTSD) is a neuropsychiatric disorder that may develop after experiencing traumatic events. Preclinical studies use various methods to induce PTSD-like models such as fear-conditioning, single-prolonged stress (SPS), restraint stress, and social defeat. Brain-derived neurotrophic factor (BDNF) is a crucial neurotrophin in mood regulation. Evidence shows BDNF changes in different neuropsychiatric disorders particularly PTSD. This review examined BDNF alterations in preclinical rodent models of PTSD where we demonstrated a wide range of paradoxical changes in BDNF. We found that the fear-conditioning model produced the most inconsistent alterations in BDNF, and suggest that conclusions drawn from these changes be approached with caution. We suggest that BDNF maladaptive changes in social defeat and restraint stress models may be related to the duration of stress, while the SPS model appears to have more consistent results. Ultimately, we propose that evaluating BDNF alterations in the process of treating PTSD symptoms may not be a reliable factor.
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Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition that develops following exposure to a traumatic event. Individuals with this condition experience numerous physiological and behavioral alterations, including intrusive memories, avoidance of trauma-related stimuli, heightened anxiety, hypervigilance, impaired cognition, elevated resting heart rate and blood pressure, and altered neuroendocrine function, to name a few. In most patients, currently available pharmacological and psychological treatments are insufficient to alleviate the array of symptoms associated with the disorder. Thus, novel treatment options that can more effectively target the core etiology of PTSD are desperately needed. Recent work demonstrating the psychoplastogenic effects of psychedelics has reinvigorated research to examine their therapeutic potential in psychiatric conditions. Psilocybin, one psychedelic found in the Psilocybe genus of mushrooms, has exhibited promising antidepressant and anxiolytic effects in preclinical and clinical studies. The purpose of this review is to summarize the existing research that has examined the behavioral effects of psilocybin and link it to potential efficacy in treating PTSD-related symptoms. The proposed mechanisms for psilocybin's effects are then explored, as are the benefits and drawbacks for the agent's therapeutic use. Finally, the challenges faced by investigators aiming to study psilocybin as a therapeutic aid in future studies are discussed in order to shed light on this budding area of research. Significance Statement Current pharmacotherapy for PTSD is insufficient. Traditional antidepressants and anxiolytics help reduce symptom severity, but nonresponse rates often reach levels greater than 50%, emphasizing the need for more effective treatment options. The goal of this review is to summarize the existing evidence for and the potential mechanisms of the antidepressant and anxiolytic effects of psilocybin, a psychedelic compound found in the Psilocybe genus of mushrooms. We then relate the observed effects to psilocybin's potential use as a treatment for PTSD.
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A large body of evidence implies the involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of autism spectrum disorders (ASDs). A deficiency of BDNF in the hippocampus and frontal cortex of BTBR mice (a model of autism) has been noted in a number of studies. Earlier, we showed that induction of BDNF overexpression in the hippocampus of BTBR mice reduced anxiety and severity of stereotyped behavior, but did not affect social interest. Here, we induced BDNF overexpression in the frontal cortex neurons of BTBR mice using an adeno-associated viral vector, which resulted in a significant increase in the social interest in the three-chamber social test. At the same time, the stereotypy, exploratory behavior, anxiety-like behavior, and novel object recognition were not affected. Therefore, we have shown for the first time that the presence of BDNF in the frontal cortex is critical for the expression of social interest in BTBR mice, since compensation for its deficiency in this structure eliminated the autism-like deficiencies in the social behavior characteristic for these animals.
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Trastorno Autístico , Factor Neurotrófico Derivado del Encéfalo , Modelos Animales de Enfermedad , Lóbulo Frontal , Conducta Social , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/genética , Lóbulo Frontal/metabolismo , Ratones , Trastorno Autístico/metabolismo , Trastorno Autístico/genética , Masculino , Conducta Animal , Ratones Endogámicos C57BLRESUMEN
Neurotrophic factors play pivotal roles in shaping brain development and function, with brain-derived neurotrophic factor (BDNF) emerging as a key regulator in various physiological processes. This review explores the intricate relationship between BDNF and anorexia nervosa (AN), a complex psychiatric disorder characterized by disordered eating behaviors and severe medical consequences. Beginning with an overview of BDNF's fundamental functions in neurodevelopment and synaptic plasticity, the review delves into recent clinical and preclinical evidence implicating BDNF in the pathophysiology of AN. Specifically, it examines the impact of BDNF polymorphisms, such as the Val66Met variant, on AN susceptibility, prognosis, and treatment response. Furthermore, the review discusses the interplay between BDNF and stress-related mood disorders, shedding light on the mechanisms underlying AN vulnerability to stress events. Additionally, it explores the involvement of BDNF in metabolic regulation, highlighting its potential implications for understanding the metabolic disturbances observed in AN. Through a comprehensive analysis of clinical data and animal studies, the review elucidates the nuanced role of BDNF in AN etiology and prognosis, emphasizing its potential as a diagnostic and prognostic biomarker. Finally, the review discusses limitations and future directions in BDNF research, underscoring the need for further investigations to elucidate the complex interplay between BDNF signaling and AN pathology.
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Anorexia Nerviosa , Biomarcadores , Factor Neurotrófico Derivado del Encéfalo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Humanos , Anorexia Nerviosa/metabolismo , Animales , PronósticoRESUMEN
OBJECTIVES: Cancer-related cognitive impairment (CRCI) is a highly prevalent and debilitating symptom reported by breast cancer survivors (BCS). The etiology of CRCI remains unclear, leading to poor symptom management. Building from prior studies, BCS with the C/C genotype of apolipoprotein E (APOE) rs7412 and the T/T genotype of brain-derived neurotrophic factor (BDNF) rs6265 were hypothesized to experience more severe CRCI. Therefore, we investigated the relationships between the severity of CRCI and polymorphisms of APOE and BDNF among BCS. METHODS: This was a subanalysis of data from a larger descriptive, correlational, and cross-sectional study. Subjective and objective CRCI were measured using the Patient-Reported Outcomes Measurement Information System and CANTAB Cambridge Cognitive assessment, respectively. Buccal swab samples were collected to evaluate the single nucleotide polymorphisms. Multivariable generalized linear regression models were used to analyze data. RESULTS: APOE rs7412 and BDNF rs6265 were significantly associated with lower self-reported cognitive abilities in a total of 353 BCS. Age was positively associated with self-reported cognitive scores, indicating that younger BCS perceived lower cognitive abilities. Individuals carrying genotype of C/T for APOE with the C/C or C/T for BDNF showed positive associations with cognitive abilities. CONCLUSIONS: Younger BCS with the C/C genotype for APOE rs7412 and the T/T genotype for BDNF rs6265 may be at risk for CRCI. Knowledge regarding predictive markers for CRCI symptoms is essential for precision symptom management. Further investigation with a longitudinal and translational design is necessary to explore the etiologies for CRCI. IMPLICATIONS FOR NURSING PRACTICE: Integrating genetic phenotyping into routine clinical practice will provide nurses with unique opportunities to understand individual susceptibilities, and how symptoms may trigger other symptoms. Further, findings from these innovative investigations will provide symptom interventionists and implementation scientists with critical data to optimize individualized strategies for symptom prevention, detection, and management.
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Apolipoproteínas E , Factor Neurotrófico Derivado del Encéfalo , Neoplasias de la Mama , Supervivientes de Cáncer , Disfunción Cognitiva , Polimorfismo de Nucleótido Simple , Humanos , Factor Neurotrófico Derivado del Encéfalo/genética , Femenino , Supervivientes de Cáncer/psicología , Persona de Mediana Edad , Neoplasias de la Mama/genética , Neoplasias de la Mama/complicaciones , Estudios Transversales , Disfunción Cognitiva/genética , Disfunción Cognitiva/etiología , Apolipoproteínas E/genética , Anciano , Adulto , GenotipoRESUMEN
Neurotrophins are important regulators of neuronal and non-neuronal functions. As such, the neurotrophins and their receptors, the tropomyosin receptor kinase (Trk) family of receptor tyrosine kinases, has attracted intense research interest and their role in multiple diseases including Alzheimer's disease has been described. Attempts to administer neurotrophins to patients have been reported, but the clinical trials have so far have been hampered by side effects or a lack of clear efficacy. Thus, much of the focus during recent years has been on identifying small molecules acting as agonists or positive allosteric modulators (PAMs) of Trk receptors. Two examples of successful discovery and development of PAMs are the TrkA-PAM E2511 and the pan-Trk PAM ACD856. E2511 has been reported to have disease-modifying effects in preclinical models, whereas ACD856 demonstrates both a symptomatic and a disease-modifying effect in preclinical models. Both molecules have reached the stage of clinical development and were reported to be safe and well tolerated in clinical phase 1 studies, albeit with different pharmacokinetic profiles. These two emerging small molecules are interesting examples of possible novel symptomatic and disease-modifying treatments that could complement the existing anti-amyloid monoclonal antibodies for the treatment of Alzheimer's disease. This review aims to present the concept of positive allosteric modulators of the Trk receptors as a novel future treatment option for Alzheimer's disease and other neurodegenerative and cognitive disorders, and the current preclinical and clinical data supporting this new concept. Preclinical data indicate dual mechanisms, not only as cognitive enhancers, but also a tentative neurorestorative function.
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AIMS: To investigate the therapeutic potential of visual stimulation (VS) and BDNF in murine experimental autoimmune uveoretinitis (EAU). MAIN METHODS: Mice were immunized by subcutaneous injection of interphotoreceptor retinoid-binding protein in Freund's complete adjuvant and intravenous injection of pertussis toxin, and were then exposed to high-contrast VS 12 h/day (days 1-14 post-immunization). EAU severity was assessed by examining clinical score, visual acuity, inflammatory markers, and immune cells in the retina. The transcriptome of activated retinal cells was determined by RNA-seq using RNA immunoprecipitated in complex with phosphorylated ribosomal protein S6. The retinal levels of protein products of relevant upregulated genes were quantified. The effect of BDNF on EAU was tested in unstimulated mice by its daily topical ocular administration (days 8-14 post-immunization). KEY FINDINGS: VS attenuated EAU development and decreased the expression of pro-inflammatory cytokines/chemokines and numbers of immune cells in the retina (n = 10-20 eyes/group for each analysis). In activated retinal cells of control mice (n = 30 eyes/group), VS upregulated genes encoding immunomodulatory neuropeptides, of which BDNF and vasoactive intestinal peptide (VIP) also showed increased mRNA and protein levels in the retina of VS-treated EAU mice (n = 6-10 eyes/group for each analysis). In unstimulated EAU mice, BDNF treatment mimicked the protective effects of VS by modulating the inflammatory and stem cell properties of Müller cells (n = 5 eyes/group for each analysis). SIGNIFICANCE: VS effectively suppresses EAU, at least through enhancing retinal levels of anti-inflammatory and neuroprotective factors, VIP and BDNF. Our findings also suggest BDNF as a promising therapeutic agent for uveitis treatment.
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Enfermedades Autoinmunes , Factor Neurotrófico Derivado del Encéfalo , Retinitis , Uveítis , Animales , Ratones , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Uveítis/metabolismo , Uveítis/tratamiento farmacológico , Uveítis/inmunología , Retinitis/tratamiento farmacológico , Retinitis/prevención & control , Retinitis/inmunología , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/metabolismo , Femenino , Retina/metabolismo , Retina/efectos de los fármacos , Ratones Endogámicos C57BL , Péptido Intestinal Vasoactivo/farmacología , Modelos Animales de Enfermedad , Citocinas/metabolismoRESUMEN
Schizophrenia is a complex neuropsychiatric disorder with positive, negative, and cognitive symptoms. In rats, sub-chronic administration of ketamine is used for the induction of schizophrenia model. Increased locomotor activity is one of the most important features of psychotic-like symptoms in rodents. On the other hand, risperidone is a potent antipsychotic medication that is approved for the treatment of schizophrenia and bipolar disorder. In the present research, we aimed to investigate the effect of sub-chronic treatment of ketamine on cognitive and behavioral functions, and brain-derived neurotrophic factor (BDNF) expression level in the prefrontal cortex. Also, we assessed the efficacy of risperidone on cognitive and behavioral impairments induced by ketamine. Possible sex differences were also measured. Ketamine was intraperitoneally injected at the dose of 30 mg/kg for five consecutive days. Risperidone was also intraperitoneally injected at the dose of 2 mg/kg. Novel object recognition memory, pain threshold, locomotor activity, rearing behavior, and BDNF level were evaluated. The results showed that ketamine injection for five consecutive days impaired the acquisition of long-term recognition memory and decreased BDNF level in the prefrontal cortex in both sexes. Also, it decreased pain threshold in females, increased rearing behavior in males, and induced hyperlocomotion with greater effect in females. On the other hand, risperidone restored or attenuated the effect of ketamine on all the behavioral effects and BDNF level. In conclusion, we suggested that there were sex differences in the effects of ketamine on pain perception, locomotion, and rearing behavior in a rat model of schizophrenia.
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Factor Neurotrófico Derivado del Encéfalo , Modelos Animales de Enfermedad , Ketamina , Corteza Prefrontal , Risperidona , Esquizofrenia , Caracteres Sexuales , Animales , Ketamina/farmacología , Ketamina/administración & dosificación , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/inducido químicamente , Esquizofrenia/fisiopatología , Masculino , Femenino , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/efectos de los fármacos , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/metabolismo , Risperidona/farmacología , Risperidona/administración & dosificación , Ratas , Antipsicóticos/farmacología , Antipsicóticos/administración & dosificación , Reconocimiento en Psicología/efectos de los fármacos , Antagonistas de Aminoácidos Excitadores/farmacología , Antagonistas de Aminoácidos Excitadores/administración & dosificación , Ratas Wistar , Conducta Animal/efectos de los fármacos , Umbral del Dolor/efectos de los fármacos , Actividad Motora/efectos de los fármacosRESUMEN
Alzheimer's disease (AD) is a neurodegenerative disease that causes physical damage to neuronal connections, leading to brain atrophy. This disruption of synaptic connections results in mild to severe cognitive impairments. Unfortunately, no effective treatment is currently known to prevent or reverse the symptoms of AD. The aim of this study was to investigate the effects of three synthetic peptides, i.e., KLVFF, RGKLVFFGR and RIIGL, on an AD in vitro model represented by differentiated SH-SY5Y neuroblastoma cells exposed to retinoic acid (RA) and brain-derived neurotrophic factor (BDNF). The results demonstrated that RIIGL peptide had the least significant cytotoxic activity to normal SH-SY5Y while exerting high cytotoxicity against the differentiated cells. The mechanism of RIIGL peptide in the differentiated SH-SY5Y was investigated based on changes in secretory proteins compared to another two peptides. A total of 380 proteins were identified, and five of them were significantly detected after treatment with RIIGL peptide. These secretory proteins were found to be related to microtubule-associated protein tau (MAPT) and amyloid-beta precursor protein (APP). RIIGL peptide acts on differentiated SH-SY5Y by regulating amyloid-beta formation, neuron apoptotic process, ceramide catabolic process, and oxidative phosphorylation and thus has the potentials to treat AD.
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Enfermedad de Alzheimer , Péptidos beta-Amiloides , Factor Neurotrófico Derivado del Encéfalo , Diferenciación Celular , Neuroblastoma , Proteínas tau , Humanos , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/farmacología , Neuroblastoma/patología , Neuroblastoma/metabolismo , Neuroblastoma/tratamiento farmacológico , Línea Celular Tumoral , Diferenciación Celular/efectos de los fármacos , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/farmacología , Proteínas tau/metabolismo , Tretinoina/farmacología , Precursor de Proteína beta-Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/genéticaRESUMEN
The brain derived-neurotrophic factor (BDNF) Val66Met polymorphism causes functional changes in BDNF, and is associated with obesity and some psychiatric disorders, but its relationship to health-related quality of life (HRQoL) remains unknown. This study examined, in youth with obesity, whether carriers of the BDNF Val66met polymorphism Met-alleles (A/A or G/A) differed from noncarriers (G/G) on HRQoL. The participants were 187 adolescents with obesity. Ninety-nine youth were carriers of the homozygous Val/Val (G/G) alleles, and 88 were carriers of the Val/Met (G/A) or Met/Met (A/A) alleles. Blood samples were drawn in the morning after an overnight fast for genotyping. HRQoL was measured using the Pediatric-Quality of Life core version. Compared to carriers of the Val66Met Val (G/G) alleles, carriers of the Met-Alleles reported significantly higher physical -HRQoL (p = 0.02), school-related HRQoL, (p = 0.05), social-related HRQoL (p = 0.05), and total HRQoL (p = 0.03), and a trend for Psychosocial-HRQoL. Research is needed to confirm our findings and determine whether carriers of the BDNF Val66Met homozygous Val (G/G) alleles may be at risk of diminished HRQoL, information that can influence interventions in a high-risk population of inactive youth with obesity.
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Factor Neurotrófico Derivado del Encéfalo , Polimorfismo de Nucleótido Simple , Calidad de Vida , Humanos , Factor Neurotrófico Derivado del Encéfalo/genética , Factor Neurotrófico Derivado del Encéfalo/sangre , Masculino , Adolescente , Femenino , Niño , Obesidad/genética , Obesidad/psicología , Obesidad Infantil/genética , Obesidad Infantil/psicologíaRESUMEN
RATIONALE: Our study aimed to unravel the unknown mechanisms behind the exceptional efficacy of Psilocybin (PSI) in treating treatment-resistant depression (TRD). Focusing on Wistar-Kyoto (WKY) rats with a TRD phenotype and Wistar (WIS) rats as a normative comparison, we investigated behavioral and neuroplasticity-related responses to PSI, striving to shed light on the distinctive features of its antidepressant effects. OBJECTIVES: We set out to assess the behavioral impact of acute and prolonged PSI administration on WKY and WIS rats, employing Novel Object Recognition (NORT), Social Interaction (SI), and Forced Swimming Test (FST). Our secondary objectives involved exploring strain-specific alterations in neuroplasticity-related parameters, including brain-derived neurotrophic factor (BDNF) and activity-regulated cytoskeleton-associated protein (Arc). METHODS: Conducting post-acute and extended assessments after a single PSI administration, we applied behavioral tests and biochemical analyses to measure serum BDNF levels and neuroplasticity-related parameters in the prefrontal cortex. Statistical analyses were deployed to discern significant differences between the rat strains and assess the impact of PSI on behavioral and biochemical outcomes. RESULTS: Our findings uncovered significant behavioral disparities between WKY and WIS rats, indicating passive behavior and social withdrawal in the former. PSI demonstrated pronounced pro-social and antidepressant effects in both strains, each with its distinctive temporal trajectory. Notably, we identified strain-specific variations in BDNF-related signaling and observed the modulation of Arc expression in WKY rats. CONCLUSIONS: Our study delineated mood-related behavioral nuances between WKY and WIS rat strains, underscoring the antidepressant and pro-social properties of PSI in both groups. The distinct temporal patterns of observed changes and the identified strain-specific neuroplasticity alterations provide valuable insights into the TRD phenotype and the mechanisms underpinning the efficacy of PSI.
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OBJECTIVE: To study the relationship between brain-derived neurotrophic factor (BDNF) and the severity of nocturnal hypoxemia in patients in the acute and early recovery period of ischemic stroke (IS). MATERIAL AND METHODS: We enrolled 44 patients (27 men, 17 women), aged 18-85 years, in the acute phase of IS. At 3-month follow-up, 35 people were examined (21 men and 14 women). In the acute period, in addition to routine diagnostic procedures, respiratory monitoring was carried out, and the serum level of BDNF was measured by enzyme-linked immunosorbent assay. BDNF level was also evaluated at 3-month follow-up visit. Neurological status and its dynamics in the acute period of stroke were assessed as part of the clinical routine according to the National Institutes of Health Stroke Scale (NIHSS) at admission and discharge. RESULTS: We found a direct correlation between the duration of hypoxemia with SpO2 less than 90% (r=0.327, p=0.035) and less than 85% (r=0.461, p=0.003) and BDNF level in the acute phase of IS. BDNF level in the acute period of IS was negatively correlated with the minimum saturation value (r=-0.328, p=0.034). There was a direct relationship between BDNF level in the early recovery period and the duration of hypoxemia with SpO2 less than 85% (r=-0.389, p=0.028). A regression model showed that BDNF level was associated with the minimum SpO2 level. No significant associations were found with indicators of sleep-disordered breathing severity, such as the apnea-hypopnea index and the oxygen desaturation index. CONCLUSION: The severity of nocturnal hypoxemia is associated with the increase in BDNF levels both in the acute and recovery periods of IS, regardless of the presence of concomitant breathing disorders during sleep.
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Factor Neurotrófico Derivado del Encéfalo , Hipoxia , Accidente Cerebrovascular Isquémico , Humanos , Masculino , Factor Neurotrófico Derivado del Encéfalo/sangre , Femenino , Persona de Mediana Edad , Anciano , Adulto , Hipoxia/sangre , Hipoxia/complicaciones , Anciano de 80 o más Años , Adolescente , Accidente Cerebrovascular Isquémico/sangre , Accidente Cerebrovascular Isquémico/complicaciones , Adulto JovenRESUMEN
The brain-derived neurotrophic factor (BDNF) plays a crucial role during neuronal development as well as during differentiation and synaptogenesis. They are important proteins present in the brain that support neuronal health and protect the neurons from detrimental signals. The results from the present study suggest BDNF expression can be increase up to ~8-fold by treating the neuroblastoma cells SHSY-5Y with an herbal extract of Oroxylum indicum (50 µg/mL) and ~5.5-fold under lipopolysaccharides (LPS)-induced inflammation conditions. The Oroxylum indicum extract (Sabroxy) was standardized to 10% oroxylin A, 6% chrysin, and 15% baicalein. In addition, Sabroxy has shown to possess antioxidant activity that could decrease the damage caused by the exacerbation of radicals during neurodegeneration. A mode of action of over expression of BDNF with and without inflammation is proposed for the Oroxylum indicum extract, where the three major hydroxyflavones exert their effects through additive or synergistic effects via five possible targets including GABA, Adenoside A2A and estrogen receptor bindings, anti-inflammatory effects, and reduced mitochondrial ROS production.
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Factor Neurotrófico Derivado del Encéfalo , Flavanonas , Inflamación , Lipopolisacáridos , Neuronas , Fármacos Neuroprotectores , Extractos Vegetales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/genética , Extractos Vegetales/farmacología , Humanos , Fármacos Neuroprotectores/farmacología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Línea Celular Tumoral , Inflamación/tratamiento farmacológico , Inflamación/inducido químicamente , Inflamación/metabolismo , Flavanonas/farmacología , Bignoniaceae/química , Regulación hacia Arriba/efectos de los fármacos , Flavonoides/farmacología , Especies Reactivas de Oxígeno/metabolismo , Antioxidantes/farmacología , Antiinflamatorios/farmacologíaRESUMEN
Objective: Although the role of brain-derived neurotrophic factor (BDNF) in allergic rhinitis and/or nasal polyps (NPs) development has been studied, the contribution of BDNF in non-allergic NPs has not been evaluated yet. This study was to investigate the possible role of BDNF in non-allergic NPs pathogenesis. Methods: The study was carried out at The Second Hospital of Shandong University from December 2020 to November 2021. The non-allergic NPs patients (n=26) and the control group (n=22) were included. Lund-Mackay CT scores, nasal endoscopy scores, and pulmonary function testing were evaluated before surgery. Tissue and serum levels of BDNF, eosinophil cationic protein (ECP), and cytokeratins 5 (CK5) were assessed between different groups. Result: The BDNF level in serum and tissue, CK5 count, and eosinophil infiltration in tissue were higher in non-allergic NPs. The eosinophils infiltration, ECP mRNA expression level, as well as BDNF mRNA level were increased in the BDNFhigh subgroup compared with BDNFlow subgroup. Significantly negative correlations between BDNF count and the situation of airway obstruction were found in non-allergic NPs. Conclusion: BDNF may have both local and systemic effects in non-allergic NPs pathogenesis. BDNF may be a possible therapeutic target or an indicator for eosinophilic NPs management.
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OBJECTIVE: To observe the clinical effect of Tongdu Tiaoshen acupuncture (acupuncture for promoting the circulation of the governor vessel and regulating the spirit) for subjective tinnitus, and explore its potential mechanism. METHODS: A total of 92 patients with subjective tinnitus were randomly divided into an acupuncture group (46 cases, 5 cases dropped out) and a medication group (46 cases, 2 cases dropped out). The acupuncture group received Tongdu Tiaoshen acupuncture at Shuigou (GV 26), Yintang (GV 24+), Shenting (GV 24), Baihui (GV 20), Fengfu (GV 16), Dazhui (GV 14) and Zhongzhu (TE 3), Tinghui (GB 2), Yifeng (TE 17) on the affected side, 30 min each time, once every other day, 3 times a week. The medication group was orally administered ginkgo biloba leaves tablets (40 mg each time) and mecobalamin tablets (0.5 mg each time), 3 times a day. Both groups were treated for 4 weeks. The scores of tinnitus severity, tinnitus loudness visual analogue scale (VAS) and depression anxiety stress scale-21(DASS-21) before and after treatment were observed in the two groups, serum level of brain-derived neurotrophic factor (BDNF) before and after treatment in the two groups was detected, and the clinical effect was evaluated in the two groups. RESULTS: After treatmentï¼the scores of tinnitus severity, tinnitus loudness VAS and DASS-21 were decreased compared with those before treatment in the two groups (P<0.01), and the scores in the acupuncture group were lower than those in the medication group (P<0.05). After treatment, the serum level of BDNF was decreased compared with that before treatment in the two groups (P<0.01), and the serum level of BDNF in the acupuncture group was lower than that in the medication group (P<0.05). The total effective rate of the acupuncture group was 82.9% (34/41), which was higher than 70.5% (31/44) in the medication group (P<0.05). CONCLUSION: Tongdu Tiaoshen acupuncture could improve the severity of tinnitus, tinnitus loudness and negative emotion in patients with subjective tinnitus. Its mechanism may be related to the regulation of serum level of BDNF and thus affect auditory central plasticity.
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Puntos de Acupuntura , Terapia por Acupuntura , Acúfeno , Humanos , Acúfeno/terapia , Masculino , Femenino , Persona de Mediana Edad , Adulto , Anciano , Factor Neurotrófico Derivado del Encéfalo/sangre , Resultado del Tratamiento , Adulto JovenRESUMEN
Chronic unpredictable mild stress (CUMS) method has been introduced as a rodent model of depression. On the other hand, olanzapine, as an antipsychotic, can induce antidepressant and antipsychotic effects. Also, olanzapine may improve cognitive functions. Both CUMS and olanzapine can also affect the expression level of brain-derived neurotrophic factor (BDNF) and synaptophysin, the molecular factors involved in synaptic function, and learning and memory. In this study, we investigated the effect of olanzapine on locomotor activity (using open field test), pain threshold (using hot plate), depressive-like behavior (using forced swim test), spatial learning and memory (using Morris water maze), and BDNF and synaptophysin hippocampal expression (using real-time PCR) in both male and female CUMS rats. CUMS was performed for three consecutive weeks. Olanzapine was also injected intraperitoneally at the dose of 5â¯mg/kg. Our data showed that olanzapine can reverse the effects of CUMS on behavioral functions and BDNF and synaptophysin expression levels in the hippocampus of both males and females. It was also shown that olanzapine effects on spatial memory, pain perception, and BDNF and synaptophysin level were stronger in females than males. In conclusion, we suggested that the therapeutic effects of olanzapine in CUMS rats may be closely related to the function of BDNF and synaptophysin. Also, the therapeutic effects of olanzapine may be stronger in females. Therefore, and for the first time, we showed that there may be a sex difference in the effects of olanzapine on behavioral and molecular changes following CUMS.
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Factor Neurotrófico Derivado del Encéfalo , Depresión , Modelos Animales de Enfermedad , Hipocampo , Olanzapina , Percepción del Dolor , Memoria Espacial , Estrés Psicológico , Sinaptofisina , Animales , Femenino , Masculino , Ratas , Antipsicóticos/farmacología , Conducta Animal/efectos de los fármacos , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/efectos de los fármacos , Depresión/tratamiento farmacológico , Depresión/metabolismo , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Trastornos de la Memoria/tratamiento farmacológico , Trastornos de la Memoria/metabolismo , Olanzapina/farmacología , Percepción del Dolor/efectos de los fármacos , Percepción del Dolor/fisiología , Memoria Espacial/efectos de los fármacos , Estrés Psicológico/metabolismo , Estrés Psicológico/tratamiento farmacológico , Sinaptofisina/metabolismo , Ratas WistarRESUMEN
This paper shows for the first time that co-transplantation of human olfactory ensheathing cells with neurotrophin-3 into spinal cord cysts is more effective for activation of remyelination than transplantation of cells with brain-derived neurotrophic factor and a combination of these two factors. The studied neurotrophic factors do not affect proliferation and migration of ensheathing cells in vitro. It can be concluded that the maximum improvement of motor function in rats receiving ensheathing cells with neurotrophin-3 is largely determined by activation of remyelination.
Asunto(s)
Factor Neurotrófico Derivado del Encéfalo , Neurotrofina 3 , Bulbo Olfatorio , Remielinización , Animales , Ratas , Neurotrofina 3/metabolismo , Humanos , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/farmacología , Remielinización/fisiología , Bulbo Olfatorio/citología , Proliferación Celular , Médula Espinal/metabolismo , Vaina de Mielina/metabolismo , Vaina de Mielina/fisiología , Células Cultivadas , Movimiento Celular , Quistes/patología , Femenino , Quistes del Sistema Nervioso Central/cirugía , Quistes del Sistema Nervioso Central/patologíaRESUMEN
Selective serotonin reuptake inhibitors (SSRIs) are widely used drugs for the treatment of depression. Citalopram is one of the most prescribed SSRIs that is useful for the treatment of depression, obsessive-compulsive disorder, and anxiety disorders. On the other hand, crocin (active constitute of saffron) has pro-cognitive and mood enhancer effects. Also, both citalopram and crocin affect the function and expression of brain-derived neurotrophic factor (BDNF) and synaptophysin, two molecular factors that are involved in cognitive functions and mood. In the present study, we aim to investigate the interaction effect of citalopram and crocin on rats' performance in the open field test (locomotor activity and anxiety-like behavior) and the shuttle box (passive avoidance memory). Citalopram was injected at the doses of 10, 30, and 50 mg/kg, and crocin was injected at the dose of 50 mg/kg; all administrations were intraperitoneal. Real-time PCR was used to assess the expression level of BDNF and synaptophysin in the hippocampus. The results showed that citalopram (30 and 50 mg/kg) impaired passive avoidance memory and decreased BDNF and synaptophysin expression in the hippocampus, while crocin reversed memory impairment, and BDNF and synaptophysin expression in the hippocampus of rats received citalopram 30 mg/kg. Also, crocin partially showed these effects in rats that received citalopram 50 mg/kg. The results of the open field test were unchanged. In conclusion, we suggested that BDNF and synaptophysin may be involved in the effects of both citalopram and crocin.
RESUMEN
BACKGROUND: Major Depressive Disorder (MDD) poses a significant challenge to global health, with current treatments often limited by efficacy and onset delays. This study explores the synergistic antidepressant-like effects of an NPY1R agonist and Ketamine, targeting their neurobiological interactions within the ventral hippocampus. RESEARCH DESIGN AND METHODS: Utilizing a preclinical model, this study administered Neuropeptide Y receptor 1 (NPY1R) agonist and Ketamine, both separately and in combination, through intracerebroventricular (icv) and intranasal (i.n.) routes. The Forced Swimming Test (FST) was employed to assess antidepressant-like activity, while in situ Proximity Ligation Assay and immunohistochemistry were used to examine NPY1R/TrkB heteroreceptor complexes and BDNF expression in the ventral dentate gyrus (DG), along with neurogenesis markers. RESULTS: The combined treatment significantly reduced immobility in the FST, indicative of enhanced antidepressant-like effects, correlated with increased formation of NPY1R/TrkB complex and brain-derived neurotrophic factor (BDNF) expression in the ventral DG. These molecular alterations were associated with increased neurogenesis. CONCLUSIONS: The coadministration of an NPY1R agonist and Ketamine in a rodent model demonstrated potentiated antidepressant responses through synergistic neurobiological pathways, including TrkB signaling and hippocampal neurogenesis. This indicates a novel therapeutic strategy for MDD, warranting further clinical investigation to fully understand its implications.