Nerve Growth Factor Levels Research Articles

Therapeutic Plasma Exchange and Multiple Sclerosis Dysregulations: Focus on the Removal of Pathogenic Circulatory Factors and Altering Nerve Growth Factor and Sphingosine-1-Phosphate Plasma Levels.

Multiple sclerosis (MS) is predominantly an immune-mediated disease of the central nervous system (CNS) of unknown etiology with a possible genetic predisposition and effect of certain environmental factors. It is generally accepted that the disease begins with an autoimmune inflammatory reaction targeting oligodendrocytes followed by a rapid depletion of their regenerative capacity with subsequent permanent neurodegenerative changes and disability. Recent research highlights the central role of B lymphocytes and the corresponding IgG and IgM autoantibodies in newly forming MS lesions. Thus, their removal along with the modulation of certain bioactive molecules to improve neuroprotection using therapeutic plasma exchange (TPE) becomes of utmost importance. Recently, it has been proposed to determine the levels and precise effects of both beneficial and harmful components in the serum of MS patients undergoing TPE to serve as markers for appropriate TPE protocols. In this review we discuss some relevant examples, focusing on the removal of pathogenic circulating factors and altering the plasma levels of nerve growth factor and sphingosine-1-phosphate by TPE. Altered plasma levels of the reviewed molecular compounds in response to TPE reflect a successful reduction of the pro-inflammatory burden at the expense of an increase in anti-inflammatory potential in the circulatory and CNS compartments.

Synthesis and secretion of Nerve Growth Factor is regulated by Nitric Oxide in bladder cells in vitro under a hyperglycemic environment

Urine samples of female patients with overactive bladder (OAB) are characterized by low levels of nerve growth factor (NGF) and elevated concentrations of nitric oxide (NO) compared to healthy controls. We therefore examined how NO might regulate NGF synthesis using rat bladder smooth muscle (SMCs) and urothelial (UROs) cells in culture. In UROs, incubation in hyperglycemic conditions to mimic insulin insensitivity present in the OAB cohort increased secretion of NO and concomitantly decreased NGF, except when the NO synthase inhibitor, l-NAME (1 mM) was present. Sodium nitroprusside (SNP) (300 μM, 24 h), a NO generator, decreased NGF levels and decreased cyclic GMP (cGMP) content, a process validated by the cGMP synthase inhibitor ODQ (100 μM). Alternatively, SNP increased mRNA of both NGF and matrix metalloproteinase-9 (MMP-9). MMP-9 knockout of UROs by Crispr-Cas9 potently decreased the effect of SNP on NGF, implying a dependent role of NO on MMP-9. On the other hand, matrix metalloproteinase-7 (MMP-7) activity was increased by SNP, which taken together with increase in NGF mRNA, suggests a compensatory mechanism. In SMCs, hyperglycemic conditions had the same effect on extracellular content of NO and NGF than in UROs. SNP also decreased NGF secretion but increased cGMP content. Stable permeable analogs of cGMP 8-(4-Chlorophenylthio)-cGMP (1 mM) and N2,2′-O-Dibutyryl-cGMP (3 mM) inhibited NGF release. NGF and MMP-9 mRNA expression was unchanged by SNP. Deletion of MMP-9 in SMCs by Crispr-Cas9 did not alter the effect of SNP. Finally, SNP decreased MMP-7 activity, diminishing the conversion of proNGF to NGF. These results demonstrate that enhanced NO secretion triggered by high glucose decreases NGF secretion through pathways unique for each cell type that involve cGMP and proteases MMP-7 and MMP-9. These results might help to explain our observations from the urine from patients with OAB associated with metabolic syndrome.

Nerve Growth Factor and Angiotensin Converting Enzyme 2 Levels in Children with Neurodevelopmental Disorders

Objective Neurodevelopmental disorders (NDDs) are the most common psychiatric disorders in childhood, and there are many factors in their etiology. In recent years, many biomarkers have been studied to elucidate the etiology of these disorders. In this study, it was aimed to investigate the levels of nerve growth factor (NGF) and angiotensin converting enzyme 2 (ACE2) in attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and intellectual disability (ID). Methods The study included 74 children with NDDs (the number of patients in ADHD, ASD and ID groups were 24, 25 and 25 respectively) and 30 healthy controls (HCs). Serum NGF and ACE2 levels were studied with ELISA kits, also complete blood count (CBC), levels of fasting glucose and serum lipids were assessed. Results ACE2 levels were found to be lower in NDD group than HCs in girls. In boys with ASD, triglyceride levels were significantly higher than other groups. Also a positive correlation was found between ACE2 and NGF levels when all sample assessed together. Conclusions This study is a premise for investigating ACE2 and NGF in NDDs. The role of these markers in ADHD, ASD, ID and other NDDs and their associations with gender should be assessed by studies in which both larger sample groups and more disorders.

Brain-derived neurotrophic factor and nerve growth factor expression in endometriosis: A systematic review and meta-analysis.

Endometriosis is diagnosed by laparoscopic surgery. The availability of biomarkers can help understand the pathophysiology and aid in the diagnosis of the condition. In this context, this review aimed to examine levels of expression of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are increased amongst patients with endometriosis and if they can serve as a potential biomarker. PubMed, CENTRAL, Scopus, Web of Science, and Embase databases were searched for studies comparing BDNF or NGF levels amongst endometriosis patients and controls. Data were pooled for serum and tissue levels of BDNF and NGF. Ten fulfilled the inclusion criteria. On comparing BDNF levels, it was noted that endometrial tissue had significantly higher expression of BDNF levels as compared to controls (SMD: 1.73 95% CI: 0.64, 2.82 I2=89%). Similarly, the meta-analysis found significantly higher serum levels of BDNF in endometriosis patients as compared to controls (SMD: 1.66 95% CI: 0.73, 2.59 I2=95%). Pooled analysis showed significantly increased levels of NGF in endometrial tissue as compared to controls (SMD: 4.15 95% CI: 0.11, 8.18 I2=98%) but with unstable results on sensitivity analysis. Only one study showed higher levels of NGF in serum amongst endometriosis patients. Limited data shows higher expression of BDNF in endometrial lesions and increased serum levels of BDNF in endometriosis patients. Similar results were noted for NGF but with very scarce data. Further research is needed to establish BDNF and NGF as suitable biomarkers for the disease.

Investigation of the protective effect of anzer propolis in cerebral ischemia-reperfusion injury.

Globally, stroke is the leading cause of disability and death. With the use of thrombolytic therapy, reperfusion injury, and its consequences came to the fore. We aimed to find out how anzer propolis, which can only be obtained in Turkey's Eastern Black Sea region, affected ischemia-reperfusion injury using biochemical and histological techniques. 32 female Wistar albino rats were divided into 4 groups, including a control group. Three of the groups underwent 30 minutes of induced ischemia via clamping of the common carotid artery, followed by ischemia-reperfusion injury through the release of the clamp. One group received no treatment, another received oral administration of 100 mg/kg of anzer propolis one hour before surgery, and the third group received oral administration of 40 mg/kg of acetylsalicylic acid just before surgery. Histopathological examination assessed apoptosis and tissue necrosis, while serum and brain tissue were evaluated for levels of nerve growth factor (NGF), Interlokin 1β (IL-1β), Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), total antioxidant capacity (TAS), and total oxidant capacity (TOS). Anzer propolis and acetylsalicylic acid significantly reduced hyperemia in vessels, vacuolization in neurons, glial cell infiltration, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positivity. The anzer propolis group had the highest NGF levels. The anzer propolis and acetylsalicylic acid groups had lower levels of TNF-a and IL-6 in the brain tissue than the ischemia-reperfusion group, while TAS levels were higher. The findings obtained in this study suggest that anzer propolis has a neuroprotective effect against ischemia-reperfusion injury and will have beneficial effects on neurodegeneration. We believe our findings will contribute to the clinical treatment of ischemia-reperfusion injury.

The Effect of Body Weight Gain with or Without Diabetes Type 2 on the Levels of Noradrenalin and Some Neurotrophins

This work aimed to study the effect of body weight gain in individuals with or without diabetes mellitus Type 2 (DMT2) on the nervous system. Seventy-five subjects participated in this study, including 25 obese patients with DMT2 (BMI≥30kg/m2), 25 obese individuals without diabetes (BMI≥30kg/m2) and normal-weight healthy (BMI˂25kg/m2). In addition to body mass index (BMI), the west/hip ratio (WHR) and total body fat (TBF%) were calculated. 10ml of blood was collected from participants and used to determine the levels of HbA1C, noradrenaline (NA), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and fasting blood glucose (FBG). The level of NGF increased while BDNF and NA levels decreased in obese with and without diabetes compared to control. Interestingly, BDNF level was significantly higher in the obese with diabetes than without. Moreover, TBF% and WHR values were significantly higher in the obese with diabetes when compared with those without diabetes. At the same time, there were no significant differences between BMI value in these two groups. BMI, TBF% and WHR significantly correlate with FBG, HbA1C and NGF and negative significant correlation with BDNFdoes not correlate; only WHR has no correlationdoes and does not correlate with NA. As well as, HbA1C has a significant correlation with the nerve markers, positive with BDNF and NGF and negative with NA, while FBG did not correlate with them. In conclusion, neurotransmitters and neurotrophin levels could use as risk factors for diabetes, and obesity could be considered as a risk factor for neuropathy as much as diabetes.

Genicular Artery Embolization for Treatment of Knee Osteoarthritis: Interim Analysis of a Prospective Pilot Trial Including Effect on Serum Osteoarthritis-Associated Biomarkers

PurposeTo characterize the safety, efficacy, and potential role of genicular artery embolization (GAE) as a disease-modifying treatment for symptomatic knee osteoarthritis (OA). Materials and MethodsThis is an interim analysis of a prospective, single-arm clinical trial of patients with symptomatic knee OA who failed conservative therapy for greater than 3 months. Sixteen patients who underwent GAE using 250-μm microspheres and had at least 1 month of follow-up were included. Six patients completed the 12-month follow-up, and 10 patients remain enrolled. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was evaluated at baseline and at 1, 3, and 12 months. Serum and plasma samples were collected for biomarker analysis. The primary end point was the percentage of patients who achieved the minimal clinically important difference (MCID) for WOMAC pain score at 12 months. Baseline and follow-up outcomes were analyzed using the Wilcoxon matched-pairs signed-rank test. ResultsTechnical success of the procedure was 100%, with no major adverse events. The MCID was achieved in 5 of the 6 (83%) patients at 12 months. The mean WOMAC pain score decreased from 8.6 ± 2.7 at baseline to 4.9 ± 2.7 (P = .001), 4.4 ± 2.8 (P < .001), and 4.7 ± 2.7 (P = .094) at 1, 3, and 12 months, respectively. There was a statistically significant decrease in nerve growth factor (NGF) levels at 12 months. The remaining 8 biomarkers showed no significant change at 12 months. ConclusionsGAE is a safe and efficacious treatment for symptomatic knee OA. Decreased NGF levels after GAE may contribute to pain reduction and slowing of cartilage degeneration.

Qinghua decoction improves chronic nonbacterial prostatitis possibly regulating the chromogranin A/nerve growth factor/tyrosine kinase A signaling pathway mediated by inflammatory factors.

To explore the mechanism by which Qinghua decoction regulates neuroendocrine inflammation in chronic nonbacterial prostatitis (CNP) model rats and provide an experimental basis for clinical treatment. The rats were randomly divided into six groups: normal control, model, Qianlie Tongyu capsule, low-dose Qinghua decoction, medium-dose Qinghua decoction, and high-dose Qinghua decoction group with six rats in each group. Rats in each group were sacrificed on the 29th day of treatment, and blood and prostate tissues were collected. Serum levels of tumor necrosis factor-alpha and interleukins 1-beta, 6, 8, and 10 (TNF-α and IL-1β, -6, -8, and -10, respectively) were measured using enzyme-linked immunosorbent assay. The pathological changes in the rat prostate tissue in each group were observed under a light microscope. The expression levels of chromogranin A (CgA), nerve growth factor (NGF), and tyrosine kinase A (TrkA) were detected using reverse transcription quantitative polymerase chain reaction. Western blotting was used to detect protein expression of CgA, NGF, and TrkA. In the model group, the prostate capsule membrane and stroma were significantly dilated with more inflammatory cells infiltrating the stroma and perivessels. TNF-α, IL-1β, -6, and -8, CgA, NGF, and TrkA levels increased, whereas the content of IL-10 decreased, which was statistically significant compared to that in the normal control group ( < 0.05). Prostate tissue cells in the high-dose group were neatly arranged with no obvious inflammatory cell infiltration. When compared with the model group, the high-dose Qinghua decoction group showed a significant improvement in these indices ( < 0.05). Qinghua decoction led to inhibition of pathological changes in the prostate tissue of rats with CNP, regulation of inflammatory cytokine expression, and inhibition in the expression of CgA, NGF, and TrkA. This mechanism may be primarily related to regulation of the CgA/NGF/TrkA signaling pathway mediated by various inflammatory factors.

Efficacy of metformin in prevention of paclitaxel-induced peripheral neuropathy in breast cancer patients: a randomized controlled trial.

Background: Paclitaxel-induced peripheral neuropathy (PN) is a serious clinical problem with no approved drug for prevention. This study aimed to examine the neuroprotective effect of metformin against paclitaxel-induced PN in breast cancer patients. Methods: Patients with confirmed breast cancer diagnosis who were planned to receive paclitaxel were randomized to receive either metformin or placebo. Both groups received the standard chemotherapy protocol for breast cancer. Patients started metformin/placebo 1week before paclitaxel initiation and continued study interventions thereafter for nine consecutive weeks. The primary outcome was the incidence of development of grade two or more paclitaxel-induced sensory PN. The PN was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). Patients' quality of life (QoL) was assessed by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACTGOG-Ntx) subscale. Pain severity was measured by the Brief Pain Inventory Short Form (BPI-SF). Serum levels of nerve growth factor (NGF) and neurotensin (NT) were measured at baseline and at the end paclitaxel treatment. Results: A total of 73 patients (36 in the metformin arm and 37 in the control arm) were evaluated. The cumulative incidence of development of grade two or more PN was significantly lower in the metformin arm (14 (38.9%) than the control arm (28 (75.7%); p = 0.001). At the end of paclitaxel treatment, patients' QoL was significantly better in the metformin arm [median (IQR) FACTGOG-Ntx subscale of (24.0 (20.5-26.5)] compared to the control arm (21.0 (18.0-24.0); p = 0.003). The metformin arm showed lower "average" and "worst" pain scores than those detected in the control arm. At the end of the paclitaxel treatment, there was a significant difference in the median serum NGF levels between the two arms, favoring metformin (p < 0.05), while NT serum levels were deemed comparable between the two study arms (p = 0.09). Conclusion: The use of metformin in breast cancer patients offered a marked protection against paclitaxel-induced PN, which translated to better patient QoL. Clinical Trial Registration: https://classic.clinicaltrials.gov/ct2/show/NCT05351021, identifier NCT05351021.

Analysis of nerve growth factor (NGF) gene methylation in patients with schizophrenia

According to the neurotrophin hypothesis, schizophrenia can be caused by neurotrophic factors. One of these neurotrophic factors is the nerve growth factor (NGF), which has a critical role in cognitive functions. The present study aimed to investigate the NGF gene promoter methylation pattern in patients with schizophrenia and healthy individuals. Participants included patients with schizophrenia (84 males and 38 females) and healthy controls (96 males and 48 females). Blood samples were collected from all of the subjects in treated tubes for DNA extraction. The determination of the methylation pattern of the NGF gene CpG island-2 was based on the principle that bisulfite treatment of DNA results in the conversion of unmethylated bases of cytosine into uracil bases. The results showed no significant difference in the DNA methylation status for the NGF gene CpG island-2 in patients with schizophrenia and healthy individuals. Also, no significant difference was observed in the methylated and unmethylated status for the NGF gene CpG island-2 region when patients were compared with clinical parameters. In addition, relative NGF mRNA expression was significantly lower in patients with schizophrenia compared to healthy controls. However, no significant difference was observed in methylated and unmethylated status in the NGF mRNA expression. Although clinical evidence indicates a decrease in serum NGF levels in patients with schizophrenia, in the present study, there was no difference in the methylation status of the NGF gene promoter CpG island-2 between patients with schizophrenia and healthy individuals.

Pingchong Jiangni recipe through nerve growth factor/transient receptor potential vanilloid 1 signaling pathway to relieve pain in endometriosis model rats

Ethnopharmacological relevancePingchong Jiangni recipe (PJR) is often used in the treatment of endometriosis (EM). This formula has been clinically validated by the State Administration of Traditional Chinese Medicine Key Specialties Collaborative Group for its therapeutic efficacy. Recently, our research team also confirmed that PJR has a shrinking effect on ovarian chocolate cysts. Additionally, PJR was also found to have a shrinking effect on EM lesions; however, the mechanism by which this effect occurs remains unclear. Aim of the studyTo explore the mechanisms by which PJR relieves pain in patients with EM. Materials and methodsA rat model of EM was established by autologous transplantation. PJR (3.78 g/kg, 7.56 g/kg, and 15.12 g/kg) was orally administered for 21 days. The rat grimace scale (RGS) score and paw withdrawal threshold (PWT) were measured at a fixed time during the experiment. Hematoxylin and eosin staining was performed to observe histopathological changes in EM rats after administration, enzyme-linked immunosorbent assay to evaluate the plasma expression of tumor necrosis factor-α (TNF-α) and nerve growth factor (NGF), and immunohistochemistry and western blotting to identify differences in the expression of pain-related factors in EM rats. ResultsThe medium-dose group of PJR (7.56 g/kg) had the best effect on relieving pain in EM rats by reducing RGS, increasing PWT, reducing the ectopic endometrium, improving the cellular structure of the lesion, and reducing TNF-α and NGF levels. However, PJR significantly decreased the expression of transient receptor potential vanilloid 1 (TRPV1), phosphorylated TRPV1 (p-TRPV1), protein kinase C (PKC), and NGF. ConclusionThe mechanism by which PJR relieves EM pain may be through the downregulation of NGF, PKC, and TRPV1 expression.

Lower Nerve Growth Factor Levels in Major Depression and Suicidal Behaviors: Effects of Adverse Childhood Experiences and Recurrence of Illness.

The present study examined the effects of ACEs and ROI on culture supernatant NGF, stem cell factor (SCF), stem cell GF (SCGF), hepatocyte GF (HGF), and macrophage colony-stimulating factor (M-CSF), in relation to a neurotoxicity (NT) cytokine profile. NGF levels are lower in MDD (p = 0.003), particularly MDMD (p < 0.001), as compared with normal controls. ROI and ACE were significantly and inversely associated with NGF (≤0.003) and the NGF/NT ratio (≤0.001), whereas there are no effects of ACEs and ROI on SCF, SCGF, HGF, or M-CSF. Lowered NGF (p = 0.003) and the NGF/NT ratio (p < 0.001) are highly significantly and inversely associated with the severity of the current depression phenome, conceptualized as a latent vector extracted from the current severity of depression, anxiety, and suicidal behaviors. We found that one validated and replicable latent vector could be extracted from NGF, ROI, and the depression phenome, which therefore constitutes a novel ROI-NGF-pathway-phenotype. ACEs explained 59.5% of the variance in the latter pathway phenotype (p < 0.001). The imbalance between decreased NGF and increased neurotoxic cytokines during the acute phase of severe depression may contribute to decreased neuroprotection, increased neuro-affective toxicity, and chronic mild inflammation.

Detection and Quantification of Neurotrophin-3 (NT-3) and Nerve Growth Factor (NGF) Levels in Early Second Trimester Amniotic Fluid: Investigation into a Possible Correlation with Abnormal Fetal Growth Velocity Patterns.

Abnormal fetal growth is associated with adverse perinatal and long-term outcomes. The pathophysiological mechanisms underlying these conditions are still to be clarified. Nerve growth factor (NGF) and neurotrophin-3 (NT-3) are two neurotrophins that are mainly involved in the neuroprotection process, namely promotion of growth and differentiation, maintenance, and survival of neurons. During pregnancy, they have been correlated with placental development and fetal growth. In this study, we aimed to determine the early 2nd trimester amniotic fluid levels of NGF and NT-3 and to investigate their association with fetal growth. This is a prospective observational study. A total of 51 amniotic fluid samples were collected from women undergoing amniocentesis early in the second trimester and were stored at -80 °C. Pregnancies were followed up until delivery and birth weight was recorded. Based on birth weight, the amniotic fluid samples were divided into three groups: appropriate for gestational age (AGA), small for gestational age (SGA), and large for gestational age (LGA). NGF and NT-3 levels were determined by using Elisa kits. NGF concentrations were similar between the studied groups; median values were 10.15 pg/mL, 10.15 pg/mL, and 9.14 pg/mL in SGA, LGA, and AGA fetuses, respectively. Regarding NT-3, a trend was observed towards increased NT-3 levels as fetal growth velocity decreased; median concentrations were 11.87 pg/mL, 15.9 pg/mL, and 23.5 pg/mL in SGA, AGA, and LGA fetuses, respectively, although the differences among the three groups were not statistically significant. Our findings suggest that fetal growth disturbances do not induce increased or decreased production of NGF and NT-3 in early second trimester amniotic fluid. The trend observed towards increased NT-3 levels as fetal growth velocity decreased shows that there may be a compensatory mechanism in place that operates in conjunction with the brain-sparing effect. Further associations between these two neurotrophins and fetal growth disturbances are discussed.

Novel Phenylethanoid Glycosides Improve Hippocampal Synaptic Plasticity via the Cyclic Adenosine Monophosphate-CREB-Brain-Derived Neurotrophic Growth Factor Pathway in APP/PS1 Transgenic Mice

Introduction: Alzheimer’s disease (AD) is a major public health concern worldwide, but there are still no drugs available that treat it effectively. Previous studies have shown that phenylethanoid glycosides have pharmacological effects, which include anti-AD properties, but the underlying mechanisms by which they ameliorate AD symptoms remain unknown. Methods: In this study, we used an APP/PS1 AD mouse model to explore the function and mechanisms underlying savatiside A (SA) and torenoside B (TB) in the treatment of AD. SA or TB (100 mg·kg-1·d-1) was orally administered to 7-month-old APP/PS1 mice for 4 weeks. Cognitive and memory functions were measured using behavioral experiments (including the Morris water maze test and the Y-maze spontaneous alternation test). Molecular biology experiments (including Western blotting, immunofluorescence, and enzyme-linked immunosorbent assays) were used to detect any corresponding changes in signaling pathways. Results: The results showed that SA or TB treatment could significantly reduce cognitive impairment in APP/PS1 mice. We also showed that chronic treatment with SA/TB could prevent spine loss, synaptophysin immunoreactivity, and neuronal loss in mice, thereby improving synaptic plasticity and moderating learning and memory deficits. SA/TB administration also promoted the expression of synaptic proteins in APP/PS1 mouse brains and upregulated phosphorylation of proteins in the cyclic adenosine monophosphate (cAMP)/CREB/brain-derived neurotrophic growth factor (BDNF) pathway that are responsible for synaptic plasticity. Additionally, chronic SA/TB treatment increased the levels of BDNF and nerve growth factor (NGF) in the brains of APP/PS1 mice. Both astrocyte and microglia volumes, as well as the generation of amyloid β, were also decreased in SA/TB-treated APP/PS1 mice compared to control APP/PS1 mice. Conclusion: In summary, SA/TB treatment was associated with activation of the cAMP/CREB/BDNF pathway and increased BDNF and NGF expression, indicating that SA/TB improves cognitive functioning via nerve regeneration. SA/TB is a promising candidate drug for the treatment of AD.

Effects of concurrent training and CoQ10 on neurotrophic factors and physical function in people with Multiple Sclerosis: a pilot study.

The present study aimed to investigate the effects of 8-week of coenzyme Q10 (CoQ10) supplementation alone or combined with concurrent training (CT) on functional capacity, serum brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in multiple sclerosis (MS) patients. Our hypothesis is that CT promotes improvements in the studied outcomes with higher results for the combination of CT and CoQ10. Randomized placebo-controlled trial. Twenty-eight patients with MS were randomly divided into 4 groups: CT+placebo, CT+CoQ10, CoQ10 and placebo. CT involved two resistance training sessions and one aerobic training session per week. CoQ10 was supplemented with 200 mg daily. Serum levels of BDNF, NGF and functional tests [timed up and go (TUG), 6-min walk (6MW), chest press, lateral pull down, leg extension, and lying leg curls one repetition maximum] were measured before and after the intervention period. CT+placebo and CT+CoQ10 significantly improved performance in TUG, 6MW, chest press, lateral pull down, leg extension, and lying leg curls, with superior results to both CoQ10 and placebo groups. Changes in TUG for CT+placebo were significantly higher than CT+CoQ10 (p<0.05). There were no significant differences in NGF and BDNF among the four groups (p >0.05). CT improves physical abilities in patient with MS, regardless CoQ10 supplementation. CT should be recommended for MS patients to increase functional capacity, but there seems to be no benefit in supplementing CoQ10.

Short-Term Irisin Treatment Enhanced Neurotrophin Expression Differently in the Hippocampus and the Prefrontal Cortex of Young Mice.

As a result of physical exercise, muscle releases multiple exerkines, such as "irisin", which is thought to induce pro-cognitive and antidepressant effects. We recently demonstrated in young healthy mice the mitigation of depressive behaviors induced by consecutive 5 day irisin administration. To understand which molecular mechanisms might be involved in such effect, we here studied, in a group of mice previously submitted to a behavioral test of depression, the gene expression of neurotrophins and cytokines in the hippocampus and prefrontal cortex (PFC), two brain areas frequently investigated in the depression pathogenesis. We found significantly increased mRNA levels of nerve growth factor (NGF) and fibroblast growth factor 2 (FGF-2) in the hippocampus and brain-derived growth factor (BDNF) in the PFC. We did not detect a difference in the mRNA levels of interleukin 6 (IL-6) and IL-1β in both brain regions. Except for BDNF in the PFC, two-way ANOVA analysis did not reveal sex differences in the expression of the tested genes. Overall, our data evidenced a site-specific cerebral modulation of neurotrophins induced by irisin treatment in the hippocampus and the PFC, contributing to the search for new antidepressant treatments targeted at single depressive events with short-term protocols.

The effects of sigma-1 agonist fluvoxamine on experimental induced tardive dyskinesia model in rats

Tardive dyskinesia (TD) is a persistent involuntary complex movement disorder that is known to occur with long-term antipsychotic treatment. Despite being a well-recognized complication of this treatment, its symptoms are often masked by the antipsychotic agents, only to become apparent upon reducing or terminating the treatment. In an effort to advance our understanding of TD pathophysiology and to identify potential therapies, the current study aimed to establish an animal model of TD by administering haloperidol to rats and to evaluate the efficacy of fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), in ameliorating TD symptoms. The study compared the behavioral and biochemical parameters of rats that were treated with either fluvoxamine, tetrabenazine, haloperidol, or saline (control group). The biochemical parameters of interest included the brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), superoxide dismutase (SOD), and malondialdehyde (MDA). To achieve the study objectives, 32 male Wistar Albino rats were assigned to four different groups. The control group received physiological saline for six weeks. The haloperidol group received 1 mg/kg/ip haloperidol for the first three weeks, followed by two weeks of saline. The haloperidol+fluvoxamine group received 1 mg/kg/ip haloperidol for the first three weeks, followed by 30 mg/kg/ip fluvoxamine. The haloperidol+tetrabenazine group was administered 1 mg/kg/ip haloperidol for the first three weeks, followed by 5 mg/kg/ip tetrabenazine. Behavioral assessments of the rats were performed by measuring vacuous chewing movements. Subsequently, samples were collected from the hippocampus, striatum, and frontal lobe tissues of the rats, and BDNF, NGF, SOD, and MDA levels were measured. The results of the study demonstrated significant differences between the groups with respect to behavioral observations. Furthermore, SOD levels in the hippocampus, as well as BDNF, NGF, and SOD levels in the striatum of the haloperidol+fluvoxamine group were significantly higher than those observed in the haloperidol group. Conversely, MDA levels in the hippocampus were significantly lower in the haloperidol+fluvoxamine group than in the haloperidol group. These findings provide evidence of the beneficial effects of fluvoxamine, acting as a sigma-1 agonist, in treating TD symptoms induced experimentally. The observed benefits were supported by the biochemical investigations performed on brain tissue samples. Therefore, fluvoxamine may be considered as a potential alternative treatment for TD in clinical practice, although further research is needed to corroborate these findings.

Neuroprotective factors in schizophrenia: BDNF, NGF, NT3, GDNF and their connection to the pathogenesis of schizophrenia. A narrative review

Introduction: There are several hypotheses of schizophrenia pathogenesis, including the neurodegenerative theory, which is supported by evidence for the decrease of neuroprotective factors’ serum levels. The proteins, that exert a protective effect on neurons and are researched concerning schizophrenia pathogenesis, include the brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin 3 (NT3), and glial cell line-derived neurotrophic factor (GDNF). This review aims to discuss the role of neuroprotective factors in the development of schizophrenia and their relevance in clinical trials. Material and methods: This review was performed by search of the PubMed, Google Scholar, and Science Direct databases from December 25th, 2022, through January 31st, 2023, using keywords: ‘schizophrenia’, ‘schizophrenia pathogenesis’, ‘neuroprotection’, ‘neurodegeneration’, ‘BDNF’, ‘NGF’, ‘NT3’, and ‘GDNF’. We considered original research papers and systematic reviews published in English or Polish. Additionally, clinical trials, which included the assessment of neuroprotective factors’ levels in schizophrenia as outcome measures, were searched for on clinicaltrials.gov. Results: Lower levels of serum BDNF have been linked to cognitive impairment in schizophrenia. In clinical trials, the assessment of serum BDNF is used as a clinical outcome measure for novel schizophrenia therapies. Schizophrenia has also been associated with reduced peripheral NGF levels. During remission, lower NGF levels correlate with higher severity of negative symptoms. Decreased NT3 and GDNF levels can also be seen, but literature reports are inconsistent. Conclusions: Neuroprotective factors are most likely related to the pathogenesis of schizophrenia. Assessing the serum level of these proteins may prove to be an invaluable element of schizophrenia management. Keywords: schizophrenia, brain-derived neurotrophic factor, nerve growth factor,neurotrophin 3, glial cell line-derived neurotrophic factor

3, 3’-diindolylmethane enhances macrophage efferocytosis and subsequently relieves visceral pain via the AhR/Nrf2/Arg-1-mediated arginine metabolism pathway

Background3, 3’-diindolylmethane (DIM), a classical aryl hydrocarbon receptor (AhR) agonist, has been shown to relieve neuropathic pain, but few studies have reported the efficacy of DIM in visceral pain under colitis condition. PurposeThis study aimed to investigate the effect and mechanism of DIM on visceral pain under colitis condition. MethodsCytotoxicity was performed using the MTT assay. RT-qPCR and ELISA assays were applied to determine the expression and release of algogenic substance P (SP), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). Flow cytometry was used to examine the apoptosis and efferocytosis. The expression of Arg-1-arginine metabolism-related enzymes was detected using western blotting assays. ChIP assays were used to examine the binding of Nrf2 to Arg-1. Mouse models of dextran sulfate sodium (DSS) were established to illustrate the effect of DIM and validate the mechanism in vivo. ResultsDIM did not directly affect expressions and release of algogenic SP, NGF and BDNF in enteric glial cells (EGCs). However, when co-cultured with DIM-pre-treated RAW264.7 cells, the release of SP and NGF was decreased in lipopolysaccharides-stimulated EGCs. Furthermore, DIM increased the number of PKH67+ F4/80+ cells in the co-culture system of EGCs and RAW264.7 cells in vitro and alleviated visceral pain under colitis condition by regulating levels of SP and NGF as well as values of electromyogram (EMG), abdominal withdrawal reflex (AWR) and tail-flick latency (TFL) in vivo, which was significantly inhibited by efferocytosis inhibitor. Subsequently, DIM was found to down-regulate levels of intracellular arginine, up-regulate levels of ornithine, putrescine and Arg-1 but not extracellular arginine or other metabolic enzymes, and polyamine scavengers reversed the effect of DIM on efferocytosis and release of SP and NGF. Moving forward, Nrf2 transcription and the binding of Nrf2 to Arg-1-0.7 kb was enhanced by DIM, AhR antagonist CH223191 abolished the promotion of DIM on Arg-1 and efferocytosis. Finally, nor-NOHA validated the importance of Arg-1-dependent arginine metabolism in DIM-alleviated visceral pain. ConclusionDIM enhances macrophage efferocytosis in an arginine metabolism-dependent manner via “AhR-Nrf2/Arg-1” signals and inhibits the release of SP and NGF to relieve visceral pain under colitis condition. These findings provide a potential therapeutic strategy for the treatment of visceral pain in patients with colitis.

Serum glial-derived neurotrophic factor and nerve growth factor levels in patients with COVID-19

Serum glial-derived neurotrophic factor and nerve growth factor levels in patients with COVID-19