Neurotrophin Levels Research Articles

Impact of sleep disorders and disease duration on neurotrophins levels in cocaine use disorder

IntroductionBrain-derived neurotrophic factor (BDNF) and its precursor proBDNF contribute to brain plasticity and neuronal remodeling. Recently, the ratio between proBDNF and BDNF (RpB) has been proposed as a possible marker in major psychiatric disorders. Convergent lines of evidence suggest neurotrophins alterations could be involved into the pathophysiology of Cocaine Use Disorder (CUD) and insomnia. The aims of the present study are to evaluate the correlations between neurotrophins levels, insomnia and clinical features among CUD patients. Materials and methodsSubjects with a moderate to severe CUD were recruited. ProBDNF, BDNF and consequently RpB values were analyzed using ELISA technique. Insomnia severity index (ISI) scale was used to assess the severity of insomnia. Sociodemographic characteristics and CUD habits (e.g., years of cocaine use) were also collected. ResultsTwenty-four subjects (mean age 39.3 ± 6.7 years) were recruited. Correlation analysis showed that lower values of RpB were associated with higher ISI score (r = −0.469; p = 0.021), longer history of cocaine use (r = −0.584, p = 0.022) and higher amount of cocaine used (r = −0.655, p = 0.004). DiscussionThese preliminary findings may offer a novel insight on neurobiological alterations sustaining cocaine use. Lower RpB, as observed both in high insomnia levels and in chronic cocaine use, could induce a neuroprotective state as a synaptic homeostatic response to chronic damage. These findings also highlight the important role of neurotrophins balance on neurobiological alterations induced by cocaine misuse and insomnia, suggesting that RpB could be considered as a marker of neurotrophic and metabolic state of neural tissue.

Resistance training and Urtica dioica increase neurotrophin levels and improve cognitive function by increasing age in the hippocampus of rats

IntroductionInflammation and oxidative stress are two major factors in accelerating brain aging. Consumption of some traditional herbs with antioxidant and anti-inflammatory properties such as Urtica dioica extract (Ud) and resistance training (RT) may be effective in controlling premature aging and memory impairment. Therefore, we hypothesized that the combined effect of RT and Ud might play an essential role in preventing memory disorders and hippocampal tissue changes caused by increasing age in rats. Methods28 male Wistar rats (24-week) were divided into 4-groups (n = 7): control (C), Ud, RT, and Ud+RT. RT groups were trained for five weeks, and Ud extract in the 0.0166 w/v concentration (50 mg/kg, oral/daily) was administered. We also examined the effects of RT and Ud on the behavioral (memory and learning), histological (the morphological changes in the dentate gyrus), and transcript aspects of hippocampal tissue. ResultsAging led to karyopyknosis in the hippocampal tissue, which was alleviated by RT and Ud supplementation. RT and Ud were accompanied by increased GPx, GSH, GAP-43, and decreased CAP-1 levels in the hippocampus. Moreover, RT and Ud led to increased NGF, BDNF, and GAP-43 levels, decreased MDA, and protection of hippocampal tissue from karyopyknosis, which was associated with cognitive improvement. However, these interventions had no significant effect on the hippocampal levels of IL-1β, SOD, and CAT. ConclusionsThese findings suggest that increasing age decreases hippocampal NGF, BDNF, and GAP-43 levels and impairs cognition, which may be reversed by regular RT and Ud extract.

Neurotrophin Signaling Impairment by Viral Infections in the Central Nervous System.

Neurotrophins, such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin 3 (NT-3), NT-4, and NT-5, are proteins involved in several important functions of the central nervous system. The activation of the signaling pathways of these neurotrophins, or even by their immature form, pro-neurotrophins, starts with their recognition by cellular receptors, such as tropomyosin receptor kinase (Trk) and 75 kD NT receptors (p75NTR). The Trk receptor is considered to have a high affinity for attachment to specific neurotrophins, while the p75NTR receptor has less affinity for attachment with neurotrophins. The correct functioning of these signaling pathways contributes to proper brain development, neuronal survival, and synaptic plasticity. Unbalanced levels of neurotrophins and pro-neurotrophins have been associated with neurological disorders, illustrating the importance of these molecules in the central nervous system. Furthermore, reports have indicated that viruses can alter the normal levels of neurotrophins by interfering with their signaling pathways. This work discusses the importance of neurotrophins in the central nervous system, their signaling pathways, and how viruses can affect them.

Ylang-ylang (Cananga odorata (Lam.) Hook. f. & Thomson) essential oil reduced neuropathic-pain and associated anxiety symptoms in mice

Ethnopharmacological relevanceYlang-ylang essential oil (YEO), obtained from the flowers of the tropical tree Cananga odorata (Lam.) Hook. f. & Thomson (family Annonaceae), has been largely used in the traditional medicine with many uses, including anxiety and altered neuronal states. Neuropathic pain is a chronic pain condition with a high incidence of comorbidities, such as anxiety, depression, and other mood disorders, that drastically affect the patient's quality of life. The currently available drugs used for the management of neuropathic pain are inadequate due to poor efficacy and tolerability, highlighting the medicinal need of a better pharmacotherapy. Several clinical studies have reported that massage or inhalation with selected essentials oils reduces symptoms associated to pain and anxiety. Aim of the studyThe aim of this study was to investigate the analgesic properties of YEO and its efficacy in reducing neuropathy-associated mood alterations. Materials and methodsThe analgesic properties were tested in the spared nerve injury (SNI) model using male mice. Anxiolytic, antidepressant, and locomotor properties were also evaluated using behavioural tests. Finally, the YEO mechanism of action was investigated in the spinal cord and hippocampus of neuropathic mice. ResultsOral administration of YEO (30 mg/kg) reduced SNI-induced neuropathic pain and ameliorates pain-related anxiety symptoms that appeared 28 days after surgery. YEO reduced the expression of MAPKs, NOS2, p-p65, markers of neuroinflammation, and promoted normalizing effect on neurotrophin levels (BDNF). ConclusionsYEO induced neuropathic pain relief and ameliorated pain-associated anxiety, representing an interesting candidate for the management of neuropathic pain conditions and pain-related comorbidities.

Impact of blood source and component manufacturing on neurotrophin content and in vitro cell wound healing.

We evaluated neurotrophin (NF) levels and their impact on in vitro cell wound healing in eye drops from differently prepared blood sources (cord blood [CB], and peripheral blood [PB]) in the same donor, to avoid intrasubject biological variability. Twenty healthy adult donor PB samples, and twenty CB samples acquired at the time of delivery were processed to obtain serum (S), platelet-rich plasma (PRP), platelet-poor plasma (PPP), and S retrieved from PRP after activation with Ca-gluconate (PRP-R). The levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), glial-derived neurotrophic factor (GDNF), fibroblast growth factor (FGF), and epidermal growth factor (EGF) were assessed with a Luminex xMAP (Luminex Corporation), and by using multikine kits from R&D system, and were statistically analysed in the eight different preparations. The impact of S, PRP, PPP, PRP-R from both sources on a cell line responding to NF supplementation (MIO-M1, UCL Institute of Ophthalmology, London, UK) was tested with a scratch wound assay, and analysed by IncuCyte S3 equipment. All the preparations from CB showed higher NF levels, except for BDNF where no difference was found as compared to PB. PRP showed higher NF levels with respect to S, PPP and PRP-R in this decreasing order. Younger donors in PB contributed with higher NF levels. The scratch assay showed different cell migration results, with a complete wound closure only recorded with the supplementation of CB-S, and a progressive reduction by using PRP, PRP-R, and PPP from both sources. Protocols of preparation and choice of blood source determine different NF levels in the final products. The therapeutic use of a natural neurotrophin pool from blood sources might have a clinical impact in several different settings. Efforts are needed to standardise the manufacturing and the product content in order to establish and modulate the posology of the final supplementation.

The neuroprotective effects of oxygen therapy in Alzheimer’s disease: a narrative review

Alzheimer’s disease (AD) is a degenerative neurological disease that primarily affects the elderly. Drug therapy is the main strategy for AD treatment, but current treatments suffer from poor efficacy and a number of side effects. Non-drug therapy is attracting more attention and may be a better strategy for treatment of AD. Hypoxia is one of the important factors that contribute to the pathogenesis of AD. Multiple cellular processes synergistically promote hypoxia, including aging, hypertension, diabetes, hypoxia/obstructive sleep apnea, obesity, and traumatic brain injury. Increasing evidence has shown that hypoxia may affect multiple pathological aspects of AD, such as amyloid-beta metabolism, tau phosphorylation, autophagy, neuroinflammation, oxidative stress, endoplasmic reticulum stress, and mitochondrial and synaptic dysfunction. Treatments targeting hypoxia may delay or mitigate the progression of AD. Numerous studies have shown that oxygen therapy could improve the risk factors and clinical symptoms of AD. Increasing evidence also suggests that oxygen therapy may improve many pathological aspects of AD including amyloid-beta metabolism, tau phosphorylation, neuroinflammation, neuronal apoptosis, oxidative stress, neurotrophic factors, mitochondrial function, cerebral blood volume, and protein synthesis. In this review, we summarized the effects of oxygen therapy on AD pathogenesis and the mechanisms underlying these alterations. We expect that this review can benefit future clinical applications and therapy strategies on oxygen therapy for AD.

Coadministration of tianeptine alters behavioral parameters and levels of neurotrophins in a chronic model of Maple Syrup Urine disease.

Maple Syrup Urine Disease (MSUD) is caused by the deficiency in the activity of the branched-chain α-ketoacid dehydrogenase complex (BCKDC), resulting in the accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine, and valine, and their respective branched-chain α-keto acids. Patients with MSUD are at high risk of developing chronic neuropsychiatric disorders; however, the pathophysiology of brain damage in these patients remains unclear. We hypothesize that MSUD can cause depressive symptoms in patients. To test our hypothesis, Wistar rats were submitted to the BCAA and tianeptine (antidepressant) administration for 21days, starting seven days postnatal. Depression-like symptoms were assessed by testing for anhedonia and forced swimming after treatments. After the last test, the brain structures were dissected for the evaluation of neutrophins. We demonstrate that chronic BCAA administration induced depressive-like behavior, increased BDNF levels, and decreased NGF levels, suggesting a relationship between BCAA toxicity and brain damage, as observed in patients with MSUD. However, the administration of tianeptine was effective in preventing behavioral changes and restoring neurotrophins levels.

Serum Levels of Growth-Associated Protein-43 and Neurotrophin-3 in Childhood Epilepsy and Their Relation to Zinc Levels

BackgroundEpilepsy is one of the most common neurological disorders, and it places a significant economic strain on the healthcare system around the world. Although the exact mechanism of epilepsy has yet to be illustrated, various pathogenic cascades involving neurotransmitters and trace elements have been reported. We aimed to investigate the serum levels of growth-associated protein-43 (GAP-43) and neurotrophin-3 (NT-3) among cohort of Egyptian children with epilepsy and correlate these biomarkers with their zinc levels.MethodsThis case–control study included 50 pediatric patients with epilepsy who were comparable with 50 controls. Neurological assessment and electroencephalogram (EEG) were done to all included children. Biochemical measurements of serum GAP-43 and NT-3 using enzyme linked immunosorbent assays (ELISA), and total antioxidant capacity (TAC) and zinc using colorimetric assays, were performed to all participants.ResultsThere was significantly frequent positive parental consanguinity among cases with significantly frequent generalized onset seizures (94%) than simple partial seizure (6%). There were significantly lower serum GAP-43 and zinc levels with significantly higher TAC among cases vs. the controls, p˂0.05 for all. There was no significant difference in the serum levels of NT-3 among epileptic children vs. the controls, p = 0.269. Serum Zn was positively correlated with GAP-43 level among epileptic children (r = 0.381, p = 0.006). Serum GAP-43 in diagnosing childhood epilepsy at cut-off point ≤ 0.6 ng/mL showed 78% sensitivity, 62% specificity, positive predictive value (PPV) = 50.6%, negative predictive value (NPP) = 84.9% with AUC = 0.574.ConclusionGAP-43 can be considered a sensitive good negative biomarker in childhood epilepsy which correlated positively with the zinc status.

Aerobic Training and Circulating Neurotrophins in Alzheimer’s Disease Patients: A Controlled Trial

ABSTRACT Objective to verify the effects of aerobic exercise training in circulating BDNF, VEGF165 and IGF-1 plasma levels and cognitive function in Alzheimer’s Disease (AD) patients. Methods 34 AD patients participated in the study, divided in two groups: Control Group (CG; n = 16) and Training Group (TG; n = 18 – Moderate aerobic training on the treadmill, three times a week, for 12 weeks). BDNF, VEGF165, and IGF-1 plasma levels were considered as a primary outcome. Secondary outcomes included cognitive functions and aerobic fitness. Results After 12 weeks, maintenance of executive functioning in the TG was found, yet no significant changes on circulating neurotrophins levels were identified. For aerobic fitness, there was an increment in TG group. Conclusion Twelve weeks of aerobic training were neither effective in improving cognitive functioning significantly, nor influential on circulating neurotrophins levels in AD patients.

Home-based aerobic training and vitamin D improve neurotrophins and inflammatory biomarkers in MS patients

BackgroundLifestyle modifications (physical activity and diet) are among the most promising strategies in multiple sclerosis (MS) rehabilitation. This study aimed to investigate the effects of combined home-based AT and Vit D on the neurotrophins level and biomarker of inflammation in MS patients during COVID-19 outbreak. MethodsIn this randomized, single-blinded, placebo-controlled trial, 38 females with MS having EDSS: 3–5 (aged 20–40 years with body mass index [BMI] of 25–30 kg/m2) were randomly assigned into four groups: AT+Vit D (n = 10), AT (n = 9), Vit D (n = 9), and Control (C n = 10). The AT program consisted of 50–70% of HRMax, 25–40 min/day, three days/wk for eight weeks. Participants in the Vit D group consumed 50,000 IU of Vit D supplement capsules per week for eight weeks. The data were analyzed through paired t-test and one-way analysis of variance and Tukey's post hoc test at the signification level of P<0.05. ResultsAT+Vit D, AT, and Vit D compared to the control, increased BDNF and NGF, and downregulated CRP, TNF-a, IL-6, and IL-1β in MS patients. Additionally, the AT+Vit D group showed significantly lower CRP, TNF-a, IL-6, and IL-1β levels and significantly higher BDNF and NGF levels compared to the AT and Vit D groups. Also, the results of this study showed significant differences between AT and Vit D groups in the variable mentioned above. ConclusionsThese findings suggest that AT+Vit D improves neurotrophin and inflammatory biomarker levels in female MS patients more effectively than AT or Vit D alone.

Regulation of AMPAR trafficking in synaptic plasticity by BDNF and the impact of neurodegenerative disease.

Research demonstrates that the neural mechanisms underlying synaptic plasticity and learning and memory involve mobilization of AMPA-type neurotransmitter receptors at glutamatergic synaptic contacts, and that these mechanisms are targeted during neurodegenerative disease. Strengthening neural transmission occurs with insertion of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) into synapses while weakening results from receptor withdrawal. A key player in the trafficking of AMPARs during plasticity and learning is the brain-derived neurotrophic factor (BDNF) signaling system. BDNF is a neurotrophic factor that supports neuronal growth and is required for learning and memory. Significantly, a primary feature of many neurodegenerative diseases is a reduction in BDNF protein as well as disrupted neuronal surface expression of synaptic AMPARs. The resulting weakening of synaptic contacts leads to synapse loss and neuronal degeneration that underlies the cognitive impairment and dementia observed in patients with progressive neurodegenerative disease such as Alzheimer's. In the face of these data, one therapeutic approach is to increase BDNF bioavailability in brain. While this has been met with significant challenges, the results of the research have been promising. In spite of this, there are currently no clinical trials to test many of these findings on patients. Here, research showing that BDNF drives AMPARs to synapses, AMPAR trafficking is essential for synaptic plasticity and learning, and that neurodegenerative disease results in a significant decline in BDNF will be reviewed. The aim is to draw attention to the need for increasing patient-directed clinical studies to test the possible benefits of increasing levels of neurotrophins, specifically BDNF, to treat brain disorders. Much is known about the cellular mechanisms that underlie learning and memory in brain. It can be concluded that signaling by neurotrophins like BDNF and AMPA-type glutamate receptor synaptic trafficking are fundamental to these processes. Data from animal models and patients reveal that these mechanisms are adversely targeted during neurodegenerative disease and results in memory loss and cognitive decline. A brief summary of our understanding of these mechanisms indicates that it is time to apply this knowledge base directly to development of therapeutic treatments that enhance neurotrophins for brain disorders in patient populations.

Prolonged Retrobulbar Local Anesthesia of the Cornea Does Not Cause Keratopathy in Mice

PurposeProlonged local anesthesia (PLA) of the cornea is currently assumed to cause neurotrophic keratitis and is strongly discouraged. We investigate whether PLA of the cornea per se causes neurotrophic keratitis.MethodsPLA of the cornea was induced in 12 female albino BALB/c mice by retrobulbar injection of a polymeric prodrug (PGS-TTX) where the site 1 sodium channel blocker tetrodotoxin (TTX) was slowly released from the polymer polyglycerol sebacate. The duration and depth of corneal anesthesia was monitored by the Cochet-Bonnet esthesiometer. Corneal injury from PLA was assessed by slit lamp examination with 2% sodium fluorescein dye, histology, corneal nerve density by immunohistochemistry with anti-β III tubulin antibody and confocal microscopy, and corneal neurotrophin levels (substance P and neurokinin A) by an enzyme-linked immunosorbent assay. PLA was also induced by topical amitriptyline (80 mM), used as a positive control for local anesthetic-induced corneal injury. Frequent ocular lubrication was provided.ResultsRetrobulbar PGS-TTX resulted in complete corneal anesthesia lasting 50.1 ± 3.6 hours and mean time to complete resolution of block of 55.1 ± 3.6 hours with no keratopathy provided lubrication was provided. Topical 80 mM amitriptyline induced complete corneal anesthesia for 24 hours and developed keratopathy. There was no difference in the histology, levels of corneal neurotrophins, and corneal nerve density between the retrobulbar PGS-TTX group and normal cornea.ConclusionsIn the absence of topical toxicity or corneal exposure, PLA of the cornea per se does not cause keratitis.Translational RelevancePLA of the cornea could be highly beneficial in acute and chronic painful corneal conditions.

The Ketogenic Diet Improves Gut-Brain Axis in a Rat Model of Irritable Bowel Syndrome: Impact on 5-HT and BDNF Systems.

Altered gut–brain communication can contribute to intestinal dysfunctions in the intestinal bowel syndrome. The neuroprotective high-fat, adequate-protein, low-carbohydrate ketogenic diet (KD) modulates the levels of different neurotransmitters and neurotrophins. The aim was to evaluate the effects of KD on levels of 5-HT, the receptors 5-HT3B and 5-HT4, the 5-HT transporter SERT, the neurotrophin BDNF, and its receptor TrkB in the colon and brain of a rat model of irritable bowel syndrome (IBS). Samples from Wistar rats exposed to maternal deprivation as newborns and then fed with a standard diet (IBS-Std) or KD (IBS-KD) for ten weeks were analyzed. As controls, unexposed rats (Ctrl-Std and Ctrl-KD) were studied. IBS-Std rats had a disordered enteric serotoninergic signaling shown by increased mucosal 5-HT content and reduced SERT, 5-HT3B, and 5-HT4 levels compared to controls. In the brain, these animals showed up-regulation of the BDNF receptor TrkB as a counteracting response to the stress-induced reduction of the neurotrophin. KD showed a dual effect in improving the altered 5-HT and BDNF systems. It down-regulated the increased mucosal 5-HT without affecting transporter and receptor levels. KD improved brain BDNF levels and established negative feedback, leading to a compensatory downregulation of TrkB to maintain a physiological steady state.

Serum Levels of Brain Derived Neurotrophic Factor, Nerve Growth Factor, Neurotrophin 3, and Glial Derived Neurotrophic Factor in Children with Specific Learning Disorder

Specific learning disorder (SLD) is a neurodevelopmental disorder that involves complex interactions of genetic, neurobiological and environmental factors, but the definite mechanisms remain mostly unknown. The possible role of neurotrophins has been implicated in the pathophysiology of various neurodevelopmental disorders. This study aimed to investigate whether serum levels of brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), nerve growth factor (NGF), and neurotrophin-3 (NT-3) in children with SLD deviate from those of neurotypical brains. Forty-four patients with SLD and 44 healthy controls aged 7--12 years were included. SLD diagnosis and severity was determined using DSM-5-based interviews and SLD clinical observation battery. Serum neurotrophins were measured using enzyme-linked immunosorbent assay. BDNF (p=0.032), NGF (p=0.029), and NT-3 (p=0.025) serum levels were significantly higher in the SLD group compared to the control group; however, serum levels of GDNF did not show any significant difference between groups. On the other hand, GDNF serum levels were significantly different between mild and severe SLD groups (p=0.007) and were lower in severe SLD subjects than in mild cases. There was also a significant correlation between patients' reading speeds and serum levels of GDNF (p=0.025), and GDNF serum levels were lower in patients with slower reading speeds. These findings suggest that neurotrophins might play a role in the pathophysiology of SLD. Increased serum levels of BDNF, NGF, and NT-3 might reflect compensatory attempts at neuroprotection against neurodevelopmental impairment.

Associations of Adverse Childhood Experiences with Executive Function and Brain-Derived Neurotrophic Factor

Adverse childhood experiences (ACEs) may predict markers of neurocognitive performance (i.e., executive function; EF) and brain health/plasticity (i.e., brain-derived neurotropic factor; BDNF). This pilot examined the magnitude of effects between: 1) ACES and EF performance, 2) ACEs and BDNF levels, and 3) EF performance and BDNF levels. We hypothesize that higher ACEs will be associated with poorer EF scores and lower BNDF levels and that lower EF scores will be associated with lower BDNF levels. Given the pilot nature of the study, an emphasis is placed on effect size vs. significance. Participants were 36 middle-aged women enrolled in the NICE SPACES trial (age=31.4 years, BMI=34.2, racially minoritized=37.9%). ACES were quantified using the 10-item Adverse Childhood Experiences Scale. EF was measured using the fluid cognition composite from the NIH Toolbox – Cognition Battery. BDNF was estimated using proBDNF levels estimated from serum collected via venipuncture. Higher ACEs levels were not directly associated with EF scores (b = 0.03, p = .854); but did show a meaningful negative beta coefficient with BDNF levels (b = -0.34, p = .053). EF scores and BDNF showed a positive coefficient that did not reach significance (b = .26, p = .122). In a modest pilot of middle-age women, higher ACEs were associated with lower BDNF, indicating greater adversity in childhood is linked to lower neurotrophins levels in adulthood. The lower BDNF levels may help explain poorer performance on cognitive tasks. Larger follow-up studies in more powered samples are warranted given the size of detected coefficients.

The level of neurotrophins in the brain of mice with urokinase gene knockout in experimental melanoma and comorbid pathology

The objective was to evaluate the levels of neurotrophins in the brain of mice with urokinase (uPA) gene knockout, carriers of B16/F10 melanoma developing in presence of comorbid pathology – chronic neurogenic pain (CNP).Methods and materials. The study included female mice of two strains: С57ВL/6 (n=40) and C57BL/6-PlautmI.IBug-ThisPlau6FDhu/GFDhu (n=28). In the main groups, CNP was created by the bilateral sciatic nerve ligation, with В16/F10 melanoma transplanted under the skin of the back 2 weeks after. The comparison groups included sham operated animals with melanoma transplantation, the control groups – sham operated animals and animals with CNP. Mice were decapitated on day 21 of the tumor growth, and the brain levels of brain neurotrophic factor (BDNF); nerve growth factor (NGF), neurotrophins 3 (NT3) and 4 (NT4) were studied by ELISA.Results. The brain of mice with uPA gene knockout demonstrated higher levels of NT3 (by 1.3 times (p=0.0146)), NT4 (by 2.6 times) and NGF-β (by 1.9 times (p=0.0021)) and lower BDNF (by 1.7 times (p=0.0203)), compared to mice without knockout. Cerebral reduction of NGF-β was a nonspecific brain response to CNP and neoplastic growth in female mice, enhanced in the combination of the pathological factors. Greater stimulation of subcutaneous melanoma growth in female mice with uPA knockout under the influence of CNP combined with a 2-fold decrease in levels of NT3 and BDNF in the brain, along with 2.2 times higher cerebral levels of NGF-β, compared to female mice without knockout.Conclusions. In female mice with uPA gene knockout compared to mice without knockout, we revealed background differences and other dynamics of neurotrophin levels in the brain at melanoma growth both alone and in combination with comorbid pathology – CNP.

Chrysin restores memory deficit in hypothyroidism mice: Behavioral, neurochemical and computational approaches involving the neurotrophinergic system

Hypothyroidism is a condition that affects multiple systems, including the central nervous system, causing, for example, cognitive deficits closely related to Alzheimer's disease. The flavonoid chrysin is a natural compound associated with neuronal improvement in several experimental models. Here, we evaluated the effect of chrysin on cognitive impairment in hypothyroid female mice by exploring neuroplasticity. Hypothyroidism was induced by continuous exposure to 0.1% methimazole (MTZ) in drinking water for 31 days. On the 32nd day, the animals showed low plasma levels of thyroid hormones (hypothyroid mice) than the control group (euthyroid mice). Subsequently, mice were intragastrically administered with vehicle or chrysin (20 mg/kg) once a day for 28 consecutive days. At the end of the treatments, behavioral tests were performed: open-field test (OFT) and morris water maze (MWM). Then, the levels of neurotrophins (BDNF and NGF) in the hippocampus and prefrontal cortex were measured and tested the affinity of chrysin with neurotrophinergic receptors through molecular docking. Hypothyroid mice showed memory deficit in the MWM and reduced neurotrophins levels in the hippocampus and prefrontal cortex, meanwhile, the chrysin treatment was able to reversed the deficit of spatial memory function and increased the levels of BDNF in hipocamppus and NGF in both structures. Additionally, molecular docking analysis showed that chrysin potentially binds to the active site of the TrkA, TrkB, and p75NTR receptors. Together, these findings suggest that chrysin reversed behavioral and neurochemical alterations associated with memory deficit induced by hypothyroidism, possibly by modulating synaptic plasticity in the neurotrophinergic system.

More than a skin disease: stress, depression, anxiety levels, and serum neurotrophins in lichen simplex chronicus

BackgroundLichen simplex chronicus is a dermatological condition due to excessive scratching, with few studies on psychoneuroimmunology. ObjectiveWe aimed to estimate the levels of stress, depression, and anxiety, and to measure serum levels of neurotrophins in patients with lichen simplex chronicus, and to correlate these parameters with the severity of the disease and pruritus. MethodsThirty-six patients with lichen simplex chronicus and 36 age- and sex-matched healthy controls were included. Each participant was administered the Hospital Anxiety and Depression Scale and Perceived Stress Scale questionnaires, along with a visual analog scale for pruritus. Levels of neurotrophins (brain-derived neurotrophic factor, neurotrophin-3, nerve growth factor, glial cell line-derived neurotrophic factor) were determined by ELISA assays. ResultsThe scores of Perceived Stress Scale-10, Hospital Anxiety and Depression Scale were statistically higher in patients (p < 0.05 for all). The serum levels of all neurotrophins were significantly lower in patients compared to healthy controls (p < 0.05 for all). Disease severity showed no correlation with all four neurotrophins. In linear regression models applied for increased visual analog scale-pruritus scores and disease severity these two variables were statistically significant predictors (p = 0.043). Study limitationsA direct causal relationship was not addressed. ConclusionLichen simplex chronicus patients are at risk of increased levels of stress, anxiety, depression, and present decreased levels of neurotrophins, that may suggest a role in the pathophysiology of this disorder.

Biochemical Assessments of Neurotrophin-3 and Zinc Involvement in the Pathophysiology of Pediatric Febrile Seizures : Biochemical Markers in Febrile Seizures.

Febrile seizures (FSs) are a common occurrence in young children and a serious concern in pediatric practice; nevertheless, the causes and mechanisms of FS are still unknown. We hypothesized a relation of neuropeptides such as neurotrophin-3 (NT-3) and growth-associated protein-43 (GAP-43) as well as zinc and the oxidant/antioxidant system with pediatric FS. The study included 100 infants categorized into 50 infants with FS and 50 febrile infants without seizures as controls. Clinical assessments, biochemical assays of NT-3 and GAP-43 using ELISA assay kits, and colorimetric measurements of TAC and Zn were performed to all participants. Overall, significant rises of the values of NT-3 and insignificant increases of GAP-43 were detected in children with FS. At the same time, zinc values and the total antioxidant capacity in serum samples were found to be decreased significantly. In addition, a negative correlation was estimated between NT-3 and zinc levels. Serum NT-3 in diagnosing febrile seizures at cutoff point > 49.62ng/L showed 100% sensitivity, 46% specificity, positive predictive value (PPV) = 48.1%, and negative predictive value (NPP) = 100% with AUC = 0.678. Significant altered circulating NT-3 and zinc levels in FS may indicate their possible role in the pathogenesis of FS. This may open a way for further research and warrants enlightening of the pathophysiological details of FS.

5,6,7 trihydroxy flavone armoured neurodegeneration caused by Quinolinic acid induced huntington’s like disease in rat striatum - reinstating the level of brain neurotrophins with special reference to cognitive-socio behaviour, biochemical and histopathological aspects

Huntington Disease (HD), a predominant Neurodegenerative Disorder which might be induced by endogenous neurotoxin called Quinolinic Acid (QA), an N-methyl-D aspartate receptor (NMDAR) agonist, the bilaterally intrastriatal administration (200 nm/2 μL of saline) offers rise to the toxic events like neuronal death, neuroinflammation by inflicting excitotoxicity and oxidative stress in the striatum of male Wistar rats by exhibiting the behavioural changes which was accessed by rotarod, open field analysis. In this study, the neuropharmacological effect of Baicalein (BC) against QA induced HD was evaluated. Baicalein (BC), scientifically 5,6,7 trihydroxy flavone present naturally in the edible plants like Scutellaria baicalensis and Oroxylum indicum possess a better neuroprotective effect in the dosage of 10 mg/kg and 30 mg/kg intraperitoneally in the striatum of HD induced rats. This study proved that BC is efficient to revive the level of enzymatic & non-enzymatic antioxidants and mitochondrial complexes by decreasing the number of inflammatory mediators such as MDA, protein carbonyls and Nitric Oxide at the significance of P < 0.01 and restores the amount of BDNF and GDNF thereby preventing the neurophysiological changes which were analysed by haematoxylin & eosin staining. Thus finally, the protective effect of Baicalein displays the up-gradation of psychological and behavioural changes induced by QA.