Mean Brain-derived Neurotrophic Factor Levels Research Articles

The Effect of Electrical Stimulation Therapy on Brain Derived Neurotrophic Factor in Patients with Tinnitus.

Introduction: The aim of this study was to determine the effect of electric stimulation therapy on brain-derived neurotrophic factor (BDNF) in patients with tinnitus. Materials and methods: In this before-after clinical trial study, 45 patients aged 30-80 years old with tinnitus were involved. The hearing threshold, loudness, and frequency of tinnitus were assessed. Tinnitus Handicap Inventory (THI) questionnaire was completed by the patients. Before holding electrical stimulation sessions, the patients were evaluated for serum brain-derived neurotrophic factor (BDNF) level. Patients underwent five electrical stimulation sessions of 20min for 5 consecutive days. After completion of electrical stimulation session, THI questionnaire was re-completed by the patients and they were evaluated for serum BDNF level. Results: Mean BDNF level before and after the intervention was (1238 ± 494.2) and (1148.2 ± 496.7), respectively (P = 0.04). Mean loudness score before and after the intervention was (6.36 ± 1.47) and (5.27 ± 1.68), respectively (P = 0.01). Mean THI score before and after the intervention was (58.21 ± 11.8) and (53.17 ± 15.19), respectively (p = 0.01). In patients with severe THI1, there was a significant difference between serum BDNF level (p = 0.019) and loudness (p = 0.003) before and after the intervention. However, in patients with mild, moderate, and very severe THI1, no such effect was observed (p > 0.05). Conclusion: According to the results of the present study, electrical stimulation therapy significantly decreased the mean plasma BDNF level in patients with tinnitus, especially in patients with severe tinnitus so it can be used as a marker to define the response to treatment and determine the severity of tinnitus in primary evaluations.

Serum brain-derived neurotrophic factor and macular perfusion in type 2 diabetes mellitus using optical coherence tomography angiography

PURPOSE: To investigate the relationship between serum brain-derived neurotrophic factor (BDNF) and changes in macular perfusion in different stages of diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA). MATERIALS AND METHODS: The study was conducted on 72 eyes of people with type 2 diabetes mellitus (DM). They were divided into five groups based on their DR stage: no DR (nDR), mild and moderate nonproliferative DR, severe nonproliferative DR, active proliferative DR (aPDR), and stable PDR. The presence or absence of diabetic maculopathy was also used to categorize the cases. All patients underwent a complete history, ophthalmological examination, OCTA imaging, and evaluation of BDNF and glycated hemoglobin A1c levels. RESULTS: The mean blood BDNF levels in the aPDR group were considerably lower than those in the nDR group (P = 0.023). In comparison to eyes without maculopathy, eyes with maculopathy had considerably decreased mean blood BDNF levels (P = 0.0004). Comparing NPDR and PDR groups to nDR as well as NPDR and PDR, a substantial decrease in average and parafoveal vessel density (VD) of the retina and choriocapillaries was seen (P = 0.02). The Foveal Avascular Zone (FAZ) acircularity index and VD were found to be significantly impacted by deteriorating DR (P = 0.001 and 0.017, respectively). It was discovered that there is a positive correlation between BDNF and the FAZ fractal dimension (P = 0.03). In diabetic eyes, there was a statistically favorable correlation between BDNF levels and best corrected visual acuity (P = 0.002). Furthermore, there was a negative relationship between DM duration and BDNF (P = 0.021). CONCLUSION: Serum BDNF levels decreased with the progression of DR and in patients with maculopathy. BDNF was found to be related to macular perfusion, particularly in the fovea.

Comparison of brain-derived neurotrophic factor among subtypes of exudative age-related macular degeneration.

To compare the levels of brain-derived neurotrophic factor (BDNF) in serum and aqueous humor (AH) in eyes with typical neovascular age-related macular degeneration (tAMD), polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP). This prospective study included 20 patients with tAMD, 20 patients with PCV, 20 patients with RAP, and 20 healthy controls. BDNF levels in the serum and AH were assessed using enzyme-linked immunosorbent assay. Serum and AH BDNF levels were significantly lower in the age-related macular degeneration groups (tAMD, PCV, and RAP) than in the control group (p < 0.05). There was no significant difference in the mean BDNF levels in the serum and AH among the different nAMD subtypes (p = 0.538). We confirmed that serum and AH BDNF levels were independent of the nAMD subtype.

Serum alpha-melanocyte-stimulating hormone (a-MSH), brain-derived neurotrophic factor (BDNF), and agouti-related protein (AGRP) levels in children with Prader-Willi or Bardet-Biedl syndromes.

Although leptin/melanocortin pathway pathologies in hypothalamus are thought to be the main cause of early-onset obesity and hyperphagia in PWS and BBS, the exact mechanism is still not known. To measure serum concentrations of a-MSH, BDNF and AGRP in a group of children with BBS or PWS. We recruited 12 subjects with PWS, 12 subjects with BBS, 28 obese controls (OC) and 26 lean controls (LC) matched for age, sex and puberty. Serum a-MSH, BDNF and AGRP levels were measured by the ELISA method. The mean a-MSH level was lower in PWS than those of OC and LC (3729 ± 1319, 5211 ± 829 and 5681 ± 565pg/ml, respectively, p < 0.001), and mean a-MSH was lower in OC than LC (p < 0.05). The mean BDNF level of PWS was higher than those of OC and LC (565 ± 122, 482 ± 102 and 391 ± 74pg/ml, respectively, p < 0.001). On the other hand, mean a-MSH level of BBS was lower than those of OC and LC (4543 ± 658, 5211 ± 829 and 5681 ± 565pg/ml, respectively, p < 0.001), and mean a-MSH was lower in OC than LC (p < 0.05). The mean BDNF level of BBS was higher than those of OC and LC (583 ± 115, 482 ± 102 and 391 ± 74pg/ml, respectively, p < 0.001). Additionally, both in PWS and BBS, the mean BDNF level was higher in OC than LC (p < 0.01). Regarding AGRP level, there was no difference both in BBS and PWS compared to OC. We found that the serum a-MSH levels of PWS and BBS groups are significantly lower compared to those of obese and lean controls. Therefore, we can speculate that the circulating a-MSH level does properly reflect its central production, and the serum a-MSH level might be a good biomarker to detect a-MSH deficiency in individuals suspected to have BBS or PWS, and also in those with POMC, PCSK1, and LEPR deficiency.

Changes in serum levels of brain-derived neurotrophic factor with electroconvulsive therapy and pharmacotherapy and its clinical correlates in male schizophrenia patients.

It has been postulated that neurotrophin dysregulation leads to disorganisation in neuronal networks, which results in schizophrenia. The current study sets out to evaluate if the finding of lower brain-derived neurotrophic factor (BDNF) levels in schizophrenia patients could be confirmed in an independent cohort and to investigate if the BDNF levels can be altered with different treatment modalities such as electroconvulsive therapy (ECT) and/or antipsychotic pharmacotherapy (PT). A total of 54 male patients with schizophrenia and 35 healthy controls were included in the study. Schizophrenia patients were subdivided into two groups as the ones who underwent ECT+PT and only PT. Clinical and sociodemographic data questionnaire, Positive and Negative Syndrome Scale (PANSS) and blood sample collection for BDNF assessment were applied to all patients (on first and last days of admissions) and healthy participants (on the day of the interview). Then, clinical parameters and blood sample outcomes were statistically analysed. Mean BDNF levels of healthy individuals were significantly higher than mean pre- and post-treatment BDNF levels in both PT only and ECT+PT groups. While serum BDNF levels did not increase after ECT+PT, there was a trend level increase in the PT only group. There was no significant correlation between the changes in serum BDNF levels with total PANSS scores in either group after treatment. We could confirm previously suggested data of lower serum BDNF levels in schizophrenia patients compared to healthy population but we could not find significant increase in serum BDNF levels with ECT+PT or only PT as some previous studies suggested.

Serum and aqueous humor levels of brain-derived neurotrophic factor in patients with primary open-angle glaucoma and normal-tension glaucoma.

This study was designed to compare the levels of brain-derived neurotrophic factor (BDNF) in the serum and aqueous humor (AH) of patients with primary open-angle glaucoma (POAG) and normal-tension glaucoma (NTG). This prospective, observational study consists of 30 patients with POAG, 30 patients with NTG, and 30 healthy controls. The serum and AH BDNF levels were assessed using an enzyme-linked immunosorbent assay. BDNF levels in serum and AH were markedly lower in the glaucoma groups (POAG and NTG) than in the control group (p <0.05). When comparing the NTG and POAG groups, the average serum BDNF level was significantly lower in the NTG group than in the POAG group (p <0.05). The difference in the mean BDNF levels in AH between the POAG and NTG groups was not statistically significant. (p = 0.538). We confirmed that serum BDNF levels were lower in patients with NTG than in those with POAG. BDNF could be a causative systemic biomarker in NTG.

Comparison of brain-derived neurotrophic factor (BDNF) serum level in inflammatory and non-inflammatory acne vulgaris

Background: Acne vulgaris is a chronic and self-limiting inflammation disorder of the pilosebaceous unit, generally manifested in adolescents with polymorphic lesions, such as comedones, papules, nodules, and cyst. Brain-derived neurotrophic factor (BDNF) is a member of neurotrophins that can be downregulated because of stress. It is suspected that a lower BDNF level is induced inflammatory process, although its relationship with acne vulgaris has not been widely studied. This study compared BDNF serum levels in the inflammatory and non-inflammatory type of acne vulgaris.Methods: This is analytical observational research with a cross-sectional design that involved 31 acne vulgaris patients with inflammatory lesions and 31 acne vulgaris patients with non-inflammatory lesions. Each subject was interviewed and going through dermatology examinations, followed by blood sampling to assessed their BDNF serum levels through the ELISA test. The collected data were analyzed statistically using an independent T-test. P&lt;0.05 was significant.Result: The mean BDNF serum levels in acne vulgaris patients were 32,53±6,32 ng/ml. In subjects with inflammatory-type lesions, the mean BDNF level is 27,55±3,31 ng/ml. While, in the non-inflammatory type lesions group, the mean BDNF is 37,51±4,37 ng/ml. The BDNF serum level is significantly lower in inflammatory-type subjects than in non-inflammatory type (p &lt; 0,001).Conclusion: There was a significant difference in serum BDNF levels between the inflammatory and non-inflammatory type acne groups.

Elevated levels of cortisol, brain-derived neurotropic factor and tissue plasminogen activator in male children with autism spectrum disorder.

Several studies demonstrated biological effects of cortisol, brain-derived neurotrophic factor (BDNF) and tissue plasminogen activator (tPA) on human metabolism and central nervous system. Our study investigated the serum levels of tPA along with BDNF and cortisol in children with autism spectrum disorder (ASD). Thirty three male children with ASD ranging in age from 2 to 15 years were selected for the study group and 27 age-matched healthy male children were selected for the control group. The ASD severity was determined by the score on the Autism Behavior Checklist (ABC). The mean cortisol levels for the study group and the control group were 79.1 ± 30.2ng/ml and 60.0 ± 25.1ng/ml, respectively. The mean BDNF levels for the study group and the control group were 5.9 ± 2.8ng/ml and 3.7 ± 1.8ng/ml, respectively. The mean tPA levels for the study group and the control group were 32.9 ± 18.5ng/ml and 25.5 ± 15.1ng/ml, respectively. Cortisol, BDNF and tPA levels were significantly higher in the study group compared to the control group (p < 0.001). There was no statistically significant effect in terms of age, ABC total and subscale scores on serum cortisol, BDNF and tPA levels in the study group (p > 0.05). It may be suggested that elevations may indicate a role in the pathogenesis of ASD or it may be the case that ASD may alter the levels or pathways of these metabolic factors. LAY SUMMARY: The underlying mechanism or a specific metabolic target relevant to autism spectrum disorder (ASD) has not yet been identified. Cortisol, brain-derived neurotrophic factor (BDNF) and tissue plasminogen activator (tPA) have biological effects on neuroplasticity but little is known about the role of cortisol and tPA-BDNF pathway in ASD. In the present study focused on male children with ASD, we have found higher blood levels of cortisol, BDNF and tPA than their healthy peers. This is the first clinical study to evaluate the serum tPA levels along with BDNF and cortisol in ASD. The results suggest that several neurotrophic and other related markers should be born in mind while examining children with ASD.

Exposure to Perfluoroalkyl Substances During Pregnancy and Fetal BDNF Level: A Prospective Cohort Study.

BackgroundHumans are widely exposed to environmental perfluoroalkyl substances (PFAS), which may affect fetal neurodevelopment. Brain-derived neurotrophic factor (BDNF) is an important factor in neurodevelopment, but its role in PFAS-induced neurotoxicity is unclear. We investigated the association between prenatal PFAS exposure and fetal BDNF level in the umbilical cord blood in a large prospective cohort.MethodsA total of 725 pregnant women who participated in the Shanghai Birth Cohort were included. 10 PFAS were measured by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS-MS) in the plasma samples of early pregnancy. The BDNF level was determined by ELISA. The concentration of total mercury (Hg) in the umbilical cord blood was tested by cold vapor atomic absorption spectrometry (AAS) and included as a main confounder, along with other covariates. Multiple linear regression was used to explore the associations between PFAS concentrations and BDNF level. Quantile-based g-computation was applied to explore the joint and independent effects of PFAS on BDNF level.ResultsThe mean BDNF level in the total population was 10797 (±4713) pg/ml. Male fetuses had a higher level than female fetuses (P<0.001). A significant positive association was observed between PFHxS and BDNF level after adjusting for potential confounders [β=1285 (95% CI: 453, 2118, P=0.003)]. No association was observed between other PFAS congeners and BDNF level. Results of the mixed exposure model showed that the joint effects of PFAS mixture were not associated with BDNF [β=447 (95% CI: -83, 978, P=0.10)], while the positive association with PFHxS exposure remained significant after controlling for other PFAS [β=592 (95% CI: 226, 958, P=0.002)]. The above associations were more prominent in male [β=773 (95% CI: 25, 1520, P= 0.04)] than female fetuses [β=105 (95% CI: -791, 1002, P= 0.82)] for the mixed effects.ConclusionsPrenatal exposure to PFHxS was associated with an increased BDNF level in the umbilical blood, especially in male fetuses.

Levels of brain-derived neurotrophic factor in patients with multiple sclerosis.

ObjectiveTo determine the levels of brain‐derived neurotrophic factor (BDNF) in the serum of patients suffering from multiple sclerosis (MS) to evaluate the potential of serum BDNF as a biomarker for MS.MethodsUsing a recently validated enzyme‐linked immunoassay (ELISA) we measured BDNF in patients with MS (pwMS), diagnosed according to the 2001 McDonald criteria and aged between 18 and 70 years, participating in a long‐term cohort study with annual clinical visits, including blood sampling, neuropsychological testing, and brain magnetic resonance imaging (MRI). The results were compared with an age‐ and sex‐matched cohort of healthy controls (HC). Correlations between BDNF levels and a range of clinical and magnetic resonance imaging variables were assessed using an adjusted linear model.ResultsIn total, 259 pwMS and 259 HC were included, with a mean age of 44.42 ± 11.06 and 44.31 ± 11.26 years respectively. Eleven had a clinically isolated syndrome (CIS), 178 relapsing remitting MS (RRMS), 56 secondary progressive MS (SPMS), and 14 primary progressive MS (PPMS). Compared with controls, mean BDNF levels were lower by 8 % (p˂0.001) in pwMS. The level of BDNF in patients with SPMS was lower than in RRMS (p = 0.004).InterpretationWe conclude that while the use of comparatively large cohorts enables the detection of a significant difference in BDNF levels between pwMS and HC, the difference is small and unlikely to usefully inform decision‐making processes at an individual patient level.

Finding prodromal frailty in a community-dwelling healthy older cohort by survey of BDNF or hand grip strength classified by BMI

Introduction : Brain-derived neurotrophic factor (BDNF) which is involved in neurogenesis, phenotypic differentiation, and neuronal survival is gaining traction in the field of gerontology research as a relevant factor in cognition and vitality in the older population. Frailty which is losing body weight or lean body mass, experiencing fatigue and loss of strength or endurance, may easily fall and fracture bones, thus becoming hospitalized and bedridden. We studied a distribution of mean BDNF levels or hand grip strengths in the classified BMI, and found the lowest BMI class of thin category has significantly (p&lt;0.01) lower mean BDNF level or mean hand grip strength than in the normal or obese 1 category of BMI. Therefore we defined the lowest BMI category “thin” as “prodromal frailty”, but not pre-frailty. We will report the findings of “prodromal frailty” and discuss how to prevent this stage from advancing to frailty. Methods : We measured serum BDNF concentrations, BMI and various health parameters in 805 elderly (aged 65–84) regional health examination participants from the Tokyo area. Their serum BDNF levels and grip strengths were divided according to BMI classification. Results : The mean serum BDNF levels increased linearly according to BMI categorization from thin (&lt;18.4 kg/m 2 ) to obese2 (30–34.9 kg/m 2 ) and decreased in the obese3 group (35–39.9 kg/m 2 ). The mean serum BDNF level in the thin category was significantly lower than that in the normal category (p&lt;0.01). The BDNF levels in the obese1 and obese2 categories did not differ significantly from that in the normal category. Mean hand grip strength (kg) was also similarly distributed to the mean BDNF level distribution in the classified BMIs. Conclusions : Elderly people in the thin BMI category had significantly lower serum BDNF levels and weaker hand grip strength than those in the normal or slightly obese categories and the people in this category is so called “prodromal frailty” but not pre-frailty. Keywords: Frailty, body mass index, brain-derived neurotrophic factor, health examination, hand grip strength

Brain-derived neurotrophic factor levels and psychopathology scores in drug-naïve first-episode psychosis.

Brain-derived neurotrophic factor (BDNF) is involved in the regulation of many neuronal processes, including neurogenesis. Therefore, it is thought to be closely associated with many psychopathologies with a neurodevelopmental basis, for example, schizophrenia. The patients admitted to the Psychiatry Department of the Faculty of Medicine with a diagnosis of non-affective drug-naïve first-episode psychosis (FEP) were included in the study. The relationship between laboratory and clinical findings and psychometric data (Positive and Negative Syndrome Scale) was examined. The study population consisted of 34 FEP and 34 healthy control (HC) volunteers. Mean BNDF levels of FEP and HC groups were 14.95 ± 6.13 and 17.89 ± 4.84 pg/ml, respectively. The difference between the groups was statistically significant (t = 2.197; p = .032). There was a negative correlation between mean BDNF levels and PANSS general psychopathology subscale scores (r = .358; p = .038), and total PANSS scores (r = .356; p = .039). There is a consensus on low serum BDNF levels both in FEP and in schizophrenia. However, it is still not clear which clinical findings are associated with lower serum BDNF levels. The relationship between BDNF levels and psychopathologies in schizophrenia has to be investigated.

Association of Serum Biomarker Levels and BDNF Gene Polymorphism with Response to Selective Serotonin Reuptake Inhibitors in Indian Patients with Major Depressive Disorder

Introduction: Depression is a major public health problem. Response to selective serotonin reuptake inhibitor (SSRI) treatment varies considerably between patients. In the context of polygenic diseases like depression, measurement of a panel of biomarkers involved in the pathophysiology of depression might help predict outcome to treatment with SSRIs. Objective: The objective was to establish the relationship between serum biomarker levels and the brain-derived neurotrophic factor (BDNF) val66met polymorphism and response to SSRIs in patients with major depressive disorder. Methods: 50 patients with moderate to severe depression were recruited from the Department of Psychiatry, Sri Ra­machandra Institute of Higher Education and Research. Blood samples were collected, and Hamilton Depression Rating Scale scoring was done at baseline and after 8 weeks of treatment with SSRIs. Baseline and post-treatment levels of high-sensitivity C-reactive protein (hsCRP), BDNF and neuregulin 1β1 (NRG1β1) were analysed using commercially available ELISA kits. Genotyping of the BDNF Val66Met polymorphism was performed using a PCR-RFLP method. Results: Following treatment, there was a significant decrease in the mean hsCRP and NRG1β1 levels and a significant increase in the mean BDNF level. Responders had significantly lower baseline hsCRP and higher baseline BDNF levels when compared to non-responders. Response rates were significantly higher in the Val/Val group when compared to the Val/Met group. Conclusions: Baseline serum levels of hsCRP and BDNF predicted response to SSRIs in major depressive disorder, and Val/Val patients responded better when compared to patients carrying the Met allele.

Association between the novel seizure quality index for the outcome prediction in electroconvulsive therapy and brain-derived neurotrophic factor serum levels

The novel Seizure Quality Index (SQI) could predict the risk of non-response and non-remission as early as after the second electroconvulsive therapy (ECT) session based the extent of several ictal parameters of the seizure in patients with depression. The association between those indices with the peripheral serum levels of brain-derived neurotrophic factor (BDNF) was evaluated in this study. It was proposed that seizure quality reflected by the SQI will be positively correlated with the levels of serum BDNF after ECT in patients with depression. We included 36 patients with a full data set, a completed course of ECT and BDNF levels before and after that ECT course. Baseline serum BDNF levels (2838.9 pg/ml ±1659.9) were lower compared to the mean BDNF levels after ECT (3206.3 pg/ml ±1532.3), but the statistical test did not reach significance (z = 1.96, p = 0.051, r = 0.23). In a sub-group analysis, the BDNF levels after ECT were positively correlated with the SQI sum score for response (rs = 0.62, p = 0.018) and for remission (rs = 0.57, p = 0.033) in patients younger than 65 years, the group, for whom the SQI has been built and validated. This suggests that one link between seizure quality and antidepressant response to ECT could be BDNF.

Evaluation of oxidative stress and brain-derived neurotrophic factor levels related to crack-use detoxification

Crack is a central nervous system stimulant extracted from the Erythroxylum coca plant. It is considered the most potent and addictive form of cocaine, and its euphoric effects are attained within a few seconds after consumption. Alteration of biological markers of oxidative stress and brain-derived neurotrophic factor (BDNF) could be related to the severity of crack withdrawal symptoms in patients undergoing rehabilitation. Thus, the objective of this study was to evaluate if the crack consumption and the drug detoxification process during 14 days in hospitalization regime was able to modify the oxidative status and BDNF levels, in male crack-abstinent patients. The crack detoxification process increased the glutathione (GSH), total thiol content (GST), nitric oxide (NO), and superoxide dismutase (SOD) levels, and reduced the mean BDNF levels. Moreover, a positive correlation was found between the number of hospital admission days and SOD values and between the GST levels and crack-use time after 14 days of detoxification. Furthermore, a negative correlation between the frequency of crack use and NO levels on the first day of hospitalization was also found. In conclusion, the results of this study indicated that crack consumption causes increased oxidative stress in drug users and that the detoxification process during 14 days was sufficient to improve oxidative parameters and antioxidant defenses of the patients, which could positively contribute to rehabilitation process. In addition, we also observed a great variability in the BDNF levels of the patients during the detoxification process, resulting in a reduction in the mean values of this neurotrophin.

Does brain-derived neurotrophic factor play a role in depression in hemodialysis patients?

Background Many end-stage renal disease (ESRD) patients undergoing hemodialysis (HD) suffer from depressive disorders as well as anxiety. These often underdiagnosed conditions not only decrease the quality of life of patients but also increase their mortality. Decrease in brain-derived neurotrophic factor (BDNF) has emerged as a marker of depression that can be used for the diagnosis and follow-up of depression in the general population. Objectives The aim of the present study was to study the role of BDNF in depression in HD patients. Patients and methods A single-center, cross-sectional study was carried out including 50 depressed (group I) and 35 nondepressed (group II) ESRD patients on maintained HD according to the Hospital Anxiety and Depression Scale. BDNF levels were measured in all patients. Result The mean BDNF level was significantly lower in depressed HD patients (2556.0±1498.15 pg/ml) in comparison with group II (9017.14±4249.60 pg/ml), with a P value less than 0.001. Serum BDNF level was also correlated negatively with both the anxiety (rs=−0.440, P Conclusion Anxiety and depression are closely linked in ESRD patients. BDNF is significantly lower in depressed HD patients and correlates negatively with both depression and anxiety. It is a useful biomarker in the detection of depression, a common often undiagnosed and undertreated condition, in ESRD.

Ethanolic extract of the Centella asiatica (L.) Urb. leaf decreases cerebellar brain-derived neurotrophic factor (BDNF) levels in rats after chronic stress

Chronic stress produces glucocorticoid-induced neurotoxicity that may lead to alterations of the brain-derived neurotrophic factor (BDNF) concentration in the brain. Cerebellum is known to be severely affected by glucocorticoids-associated oxidative damage. Centella asiatica (L.) Urb. may protect neurons from oxidative damage. This study aimed to investigate the effect of ethanolic extract of C. asiatica (L.) Urb. leaf on the rat cerebellar BDNF levels following stress. Twenty young-adult male Sprague Dawley rats were randomly assigned into four experimental groups. The stress control group received aquadest, and the other groups were treated with different doses of the C. asiatica (L.) Urb. extract i.e 150 (CeA150), 300 (CeA300) and 600 (CeA600) mg/kg body weight/day orally, respectively and followed by chronic footshock stress for 28 days. Upon completion of the experimental period, all animals were sacrificed and the cerebellar was isolated. The BDNF levels from the cerebellar tissue lysate was measured using ELISA. The mean BDNF levels of the cerebellar tissue in the stress control, CeA150, CeA300 and CeA600 groups were 1217.10±301.40; 771.46±241.45; 757.05±268.29; and 627.00±246.02 pg/mL, respectively. Post-hoc analysis showed a significant difference between the control and treatment groups (p< 0.05). In conclusion, the ethanolic extracts of the C. asiatica (L.) Urb. leaf decrease the cerebellar BDNF levels in rats after chronic stress.

Plasma Brain-Derived Neurotrophic Factor Levels in Newborn Infants with Neonatal Abstinence Syndrome.

Brain-derived neurotrophic factor (BDNF) is a type of growth factor that promotes growth and survival of neurons. Fetal exposure to opiates can lead to postnatal withdrawal syndrome, which is referred as neonatal abstinence syndrome (NAS). Preclinical and clinical studies have shown an association between opiates exposure and alteration in BDNF expression in the brain and serum levels in adult. However, to date, there are no data available on the effects of opiate exposure on BDNF levels in infant who are exposed to opiates in utero and whether BDNF level may correlate with the severity of NAS. To compare plasma BDNF levels among NAS and non-NAS infants and to determine the correlation of BDNF levels and the severity of NAS. This is a prospective cohort study with no intervention involved. Infants ≥35 weeks of gestation were enrolled. BDNF level was measured using enzyme-linked immunosorbent assay technique from blood samples drawn within 48 h of life. The severity of NAS was determined by the length of hospital stay, number of medications required to treat NAS. 67 infants were enrolled, 34 NAS and 33 non-NAS. Mean gestational age did not differ between the two groups. Mean birth weight of NAS infants was significantly lower than the non-NAS infants (3,070 ± 523 vs. 3,340 ± 459 g, p = 0.028). Mean BDNF level in NAS group was 252.2 ± 91.6 ng/ml, significantly higher than 211.3 ± 66.3 ng/ml in the non-NAS group (p = 0.04). There were no differences in BDNF levels between NAS infants that required one medication vs. more than one medication (254 ± 91 vs. 218 ± 106 ng/ml, p = 0.47). There was no correlation between the BDNF levels and length of hospital stay (p = 0.68) among NAS infants. Overall, there were no significant correlations between BDNF levels and NAS scores except at around 15 h after admission (correlation 0.35, p = 0.045). Plasma BDNF level was significantly increased in NAS infants during the first 48 h when compared to non-NAS infants. The correlations between plasma BDNF levels and the severity of NAS warrant further study. These results suggest that BDNF may play a neuromodulatory role during withdrawal after in utero opiate exposure.

Association between serum levels of glutamate and neurotrophic factors and response to clozapine treatment

Clozapine is the only available therapy for about 30% of schizophrenia patients otherwise refractory to antipsychotics. Unfortunately, the mechanism of action of the drug is still unknown and there are no biomarkers that can predict a positive response to clozapine. We aimed to examine serum neurotrophins and glutamate levels as putative biomarkers for clozapine response based on the hypothesized mode-of-action of the compound. Blood samples of 89 chronic schizophrenia patients maintained on clozapine were analyzed in a cross-sectional design. Serum brain derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), neurotrophic growth factor (NGF), glial derived neurotrophic factor (GDNF) and glutamate were determined. Differences between responders and non-responders to clozapine and correlation between clinical and biological measures were analyzed. Our sample consisted of 54 (61%) responders and 35 (39%) non-responders. Responders had higher mean BDNF levels than non-responders (2066±814 vs. 1668±820pg/ml, p<0.05. respectively) and higher serum glutamate levels (1.61±2.2 vs. 0.66±0.9pg/ml, respectively, p<0.05). Furthermore, there was a significant correlation between serum glutamate levels and positive symptoms among the clozapine-responder group (rho=0.47, p<0.005). High serum levels of BDNF and glutamate were associated with response to clozapine, while glutamate levels correlated with the psychosis severity in clozapine responders only. Large-scale, prospective longitudinal studies are needed to support these findings and the assumption that serum glutamate and BDNF can discriminate between clozapine responders and non-responders.

Brain-derived neurotrophic factor in patients with advanced age-related macular degeneration.

To investigate the serum level of the brain-derived neurotrophic factor (BDNF) in age-related macular degeneration (AMD) and healthy control subjects. The disruption in the tight balance of neuroinflammatory and neuroprotective processes in an immune-privileged site like retina is proposed to contribute to the pathogenesis of AMD. One of the main neuroprotective mediators in the central nervous system is BDNF with its serum level notably affected in several neurodegenerative disorders. Thirty-six patients with AMD and 36 age-matched controls were enrolled in this study. The serum level of BDNF was measured using the enzyme-linked immunosorbent assay method. Results were analyzed to compare case and control values. Comparisons were also made between the BDNF level of wet- vs dry-AMD, and male vs female patients and controls. Analysis of variance (ANOVA) and Student's t-test were employed to analyze the data. The mean BDNF levels in AMD group were significantly higher than the control group. Furthermore, our analysis revealed greater BDNF values in all AMD subgroups compared to controls (P=0.004, 0.005, 0.001 and 0.02 for male wet-AMD, male dry-AMD, female wet-AMD and female dry-AMD vs controls, respectively). The BDNF level however did not vary between wet- and dry-AMD patients (P=0.74). While within-group comparisons in males and females of AMD and control groups did not show any difference in BDNF (P=0.16, 0.64 and 0.85 for wet-AMD, dry-AMD and control groups, respectively), between-group data showed a higher mean BDNF in both male and female AMD subjects than their peer controls. This study demonstrated that the serum BDNF level is different in patients with AMD as compared to subjects without AMD. Future attempts should be done to unravel beneficial or deleterious effect of this neurotrophin in the pathogenesis of AMD.