Possible Role Of Brain-derived Neurotrophic Factor Research Articles

Up-regulation of systemic and local BDNF in non-allergic Nasal Polyps in China.

Although the role of brain-derived neurotrophic factor (BDNF) in allergic rhinitis and/or nasal polyps (NPs) development has been studied, the contribution of BDNF in non-allergic NPs has not been evaluated yet. This study was to investigate the possible role of BDNF in non-allergic NPs pathogenesis. The study was carried out at The Second Hospital of Shandong University from December 2020 to November 2021. The non-allergic NPs patients (n=26) and the control group (n=22) were included. Lund-Mackay CT scores, nasal endoscopy scores, and pulmonary function testing were evaluated before surgery. Tissue and serum levels of BDNF, eosinophil cationic protein (ECP), and cytokeratins 5 (CK5) were assessed between different groups. The BDNF level in serum and tissue, CK5 count, and eosinophil infiltration in tissue were higher in non-allergic NPs. The eosinophils infiltration, ECP mRNA expression level, as well as BDNF mRNA level were increased in the BDNFhigh subgroup compared with BDNFlow subgroup. Significantly negative correlations between BDNF count and the situation of airway obstruction were found in non-allergic NPs. BDNF may have both local and systemic effects in non-allergic NPs pathogenesis. BDNF may be a possible therapeutic target or an indicator for eosinophilic NPs management.

Association between NTRK2 Polymorphisms, Hippocampal Volumes and Treatment Resistance in Major Depressive Disorder.

Despite the increasing availability of antidepressant drugs, a high rate of patients with major depression (MDD) does not respond to pharmacological treatments. Brain-derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) signaling is thought to influence antidepressant efficacy and hippocampal volumes, robust predictors of treatment resistance. We therefore hypothesized the possible role of BDNF and neurotrophic receptor tyrosine kinase 2 (NTRK2)-related polymorphisms in affecting both hippocampal volumes and treatment resistance in MDD. A total of 121 MDD inpatients underwent 3T structural MRI scanning and blood sampling to obtain genotype information. General linear models and binary logistic regressions were employed to test the effect of genetic variations related to BDNF and NTRK2 on bilateral hippocampal volumes and treatment resistance, respectively. Finally, the possible mediating role of hippocampal volumes on the relationship between genetic markers and treatment response was investigated. A significant association between one NTRK2 polymorphism with hippocampal volumes and antidepressant response was found, with significant indirect effects. Our results highlight a possible mechanistic explanation of antidepressant action, possibly contributing to the understanding of MDD pathophysiology.

BDNF Val66Met polymorphism is associated with consolidation of episodic memory during sleep

The brain-derived neurotrophic factor (BDNF) is an essential regulator of synaptic plasticity, a candidate neurobiological mechanism underlying learning and memory. A functional polymorphism in the BDNF gene, Val66Met (rs6265), has been linked to memory and cognition in healthy individuals and clinical populations. Sleep contributes to memory consolidation, yet information about the possible role of BDNF in this process is scarce. To address this question, we investigated the relationship between the BDNF Val66Met genotype and consolidation of episodic declarative and procedural (motor) non-declarative memories in healthy adults. The carriers of Met66 allele, as compared with Val66 homozygotes, showed stronger forgetting overnight (24 h after encoding), but not over shorter time (immediately or 20 min after word list presentation). There was no effect of Val66Met genotype on motor learning. These data suggest that BDNF plays a role in neuroplasticity underlying episodic memory consolidation during sleep.

Association of plasma brain-derived neurotrophic factor levels and frailty in community-dwelling older adults

Brain-derived neurotrophic factor (BDNF), an exercise-induced neurotrophin, is an important factor in memory consolidation and cognitive function. This study evaluates the association between plasma BDNF levels and frailty in community-dwelling older adults. Plasma BDNF levels were analyzed in a total of 302 individuals aged 70–84 years from the Korean Frailty and Aging Cohort Study. There were 30 (9.9%) participants with frailty. They were older and had a higher prevalence of dementia and depression than those without frailty. There were no differences in the proportion of male sex between the frail and non-frail groups. Plasma BDNF levels were significantly lower in participants with frailty than in those without frailty. The presence of frailty was significantly associated with plasma BDNF levels (odds ratio 0.508, 95% confidence interval 0.304–0.849) as well as age, hemoglobin, and the presence of dementia, and depression. After adjustment for confounding factors, the significant association between plasma BDNF and frailty was maintained (0.495, 0.281–0.874). This association remained consistent after exclusion of individuals with dementia, depression, stroke, diabetes, and osteoporosis. Plasma BDNF levels were significantly associated with frailty in community-dwelling older adults. Our study may suggest the possible role of BDNF as a novel biomarker of frailty.

Localization of BDNF and Calretinin in Olfactory Epithelium and Taste Buds of Zebrafish (Danio rerio)

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family and it is involved in several fundamental functions in the central and peripheral nervous systems, and in sensory organs. BDNF regulates the chemosensory systems of mammals and is consistently expressed in those organs. In zebrafish, the key role of BDNF in the biology of the hair cells of the inner ear and lateral line system has recently been demonstrated. However, only some information is available about its occurrence in the olfactory epithelium, taste buds, and cutaneous isolated chemosensory cells. Therefore, this study was undertaken to analyze the involvement of BDNF in the chemosensory organs of zebrafish during the larval and adult stages. To identify cells displaying BDNF, we compared the cellular pattern of BDNF-displaying cells with those immunoreactive for calretinin and S100 protein. Our results demonstrate the localization of BDNF in the sensory part of the olfactory epithelium, mainly in the ciliated olfactory sensory neurons in larvae and adult zebrafish. Intense immunoreaction for BDNF was also observed in the chemosensory cells of oral and cutaneous taste buds. Moreover, a subpopulation of olfactory sensory neurons and chemosensory cells of olfactory rosette and taste bud, respectively, showed marked immunopositivity for calcium-binding protein S100 and calretinin. These results demonstrate the possible role of BDNF in the development and maintenance of olfactory sensory neurons and sensory cells in the olfactory epithelium and taste organs of zebrafish during all stages of development.

Brain-derived neurotrophic factor produced long-term synaptic enhancement in the anterior cingulate cortex of adult mice

Previous studies have demonstrated that brain-derived neurotrophic factor (BDNF) is one of the diffusible messengers for enhancing synaptic transmission in the hippocampus. Less information is available about the possible roles of BDNF in the anterior cingulate cortex (ACC). In the present study, we used 64-electrode array field recording system to investigate the effect of BDNF on ACC excitatory transmission. We found that BDNF enhanced synaptic responses in a dose-dependent manner in the ACC in C57/BL6 mice. The enhancement was long-lasting, and persisted for at least 3 h. In addition to the enhancement, BDNF also recruited inactive synaptic responses in the ACC. Bath application of the tropomyosin receptor kinase B (TrkB) receptor antagonist K252a blocked BDNF-induced enhancement. L-type voltage-gated calcium channels (L-VGCC), metabotropic glutamate receptors (mGluRs), but not NMDA receptors were required for BDNF-produced enhancement. Moreover, calcium-stimulated adenylyl cyclase subtype 1 (AC1) but not AC8 was essential for the enhancement. A selective AC1 inhibitor NB001 completely blocked the enhancement. Furthermore, BDNF-produced enhancement occluded theta burst stimulation (TBS) induced long-term potentiation (LTP), suggesting that they may share similar signaling mechanisms. Finally, the expression of BDNF-induced enhancement depends on postsynaptic incorporation of calcium-permeable AMPA receptors (CP-AMPARs) and protein kinase Mζ (PKMζ). Our results demonstrate that cortical BDNF may contribute to synaptic potentiation in the ACC.

Left lateral parietal rTMS improves cognition and modulates resting brain connectivity in patients with Alzheimer’s disease: Possible role of BDNF and oxidative stress

Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive neuromodulation technique which is increasingly used for cognitive impairment in Alzheimer’s Disease (AD). Although rTMS has been shown to modify Brain-Derived Neurotrophic Factor (BDNF) and oxidative stress levels in many neurological and psychiatric diseases, there is still no study evaluating the relationship between memory performance, BDNF, oxidative stress, and resting brain connectivity following rTMS in Alzheimer's patients. Furthermore, there are increasing clinical data showing that the stimulation of strategic brain regions may lead to more robust improvements in memory functions compared to conventional rTMS. In this study, we aimed to evaluate the possible disease-modifying effects of rTMS on the lateral parietal cortex in AD patients who have the highest connectivity with the hippocampus. To fill the mentioned research gaps, we have evaluated the relationships between resting-state Functional Magnetic Resonance Imaging (fMRI), cognitive scores, blood BDNF levels, and total oxidative/antioxidant status to explain the therapeutic and potential disease-modifying effects of rTMS which has been applied at 20 Hz frequencies for two weeks. Our results showed significantly increased visual recognition memory functions and clock drawing test scores which were associated with elevated peripheral BDNF levels, and decreased oxidant status after two weeks of left lateral parietal TMS stimulation. Clinically our findings suggest that the left parietal region targeted rTMS application leads to significant improvement in familiarity-based cognition associated with the network connections between the left parietal region and the hippocampus.

Brain-derived neurotrophic factor in patients with acute coronary syndrome

Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor highly expressed in coronary plaques, particularly in macrophages, and in activated platelets. Thus, a possible role in the pathogenesis of acute coronary syndrome (ACS) has been suggested. We evaluated systemic BDNF levels according to the different clinical presentations of ACS. Moreover, we assessed the relationship between BDNF levels and the presence of optical coherence tomography (OCT)-defined macrophage infiltrates (MØI) and healed plaques along the culprit vessel. We enrolled consecutive patients presenting with ST-elevation myocardial infarction (STEMI) or non-ST-elevation (NSTE)-ACS. Serum BDNF levels were assessed by enzyme-linked immunosorbent assay. Plaque characteristics of the culprit vessel were assessed by OCT. Among 126 ACS patients (median age 68.00, interquartile range [IQR] 59.75-75.25 years, male 74.6%, 71 (56.3%) were NSTE-ACS and 55 (43.7%) were STEMI. BDNF levels were higher in STEMI patients compared to NSTE-ACS. OCT assessment was performed in 53 (42.1%) patients. Patients with MØI (n = 27) had higher BDNF levels compared to patients without MØI. Furthermore, patients with healed plaques (n = 13) had lower BDNF levels than patients without healed plaques. At multivariate regression analysis BDNF levels independently predicted the presence of MØI (odds ratio [OR] = 2.856; 95% confidence interval [CI] [1.151-7.090], P = 0.024) and the absence of healed plaques (OR = 0.438, 95% CI [0.185-0.992], P= 0.050). Among ACS patients, BDNF levels were higher in patients with STEMI. Moreover, BDNF levels were independently associated with MØI and with the absence of healed plaques along the culprit vessel, suggesting a possible role of BDNF in promoting plaque inflammation, destabilization and occlusive thrombosis.

Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer

Brain-derived neurotrophic factor (BDNF) is one of the most distributed and extensively studied neurotrophins in the mammalian brain. BDNF signals through the tropomycin receptor kinase B (TrkB) and the low affinity p75 neurotrophin receptor (p75NTR). BDNF plays an important role in proper growth, development, and plasticity of glutamatergic and GABAergic synapses and through modulation of neuronal differentiation, it influences serotonergic and dopaminergic neurotransmission. BDNF acts as paracrine and autocrine factor, on both pre-synaptic and post-synaptic target sites. It is crucial in the transformation of synaptic activity into long-term synaptic memories. BDNF is considered an instructive mediator of functional and structural plasticity in the central nervous system (CNS), influencing dendritic spines and, at least in the hippocampus, the adult neurogenesis. Changes in the rate of adult neurogenesis and in spine density can influence several forms of learning and memory and can contribute to depression-like behaviors. The possible roles of BDNF in neuronal plasticity highlighted in this review focus on the effect of antidepressant therapies on BDNF-mediated plasticity. Moreover, we will review data that illustrate the role of BDNF as a potent protective factor that is able to confer protection against neurodegeneration, in particular in Alzheimer’s disease. Finally, we will give evidence of how the involvement of BDNF in the pathogenesis of brain glioblastoma has emerged, thus opening new avenues for the treatment of this deadly cancer.

Serum BDNF's Role as a Biomarker for Motor Training in the Context of AR-Based Rehabilitation after Ischemic Stroke.

Background: brain-derived neurotrophic factor (BDNF) may play a role during neurorehabilitation following ischemic stroke. This study aimed to elucidate the possible role of BDNF during early recovery from ischemic stroke assisted by motor training. Methods: fifty patients were included after acute recovery from ischemic stroke: 21 first received classical rehabilitation followed by ‘motor rehabilitation using motion sensors and augmented reality’ (AR-rehabilitation), 14 only received AR-rehabilitation, and 15 were only observed. Serum BDNF levels were measured on the first day of stroke, on the 14th day, before AR-based rehabilitation (median, 45th day), and after the AR-based rehabilitation (median, 82nd day). Motor impairment was quantified clinically using the Fugl–Meyer scale (FMA); functional disability and activities of daily living (ADL) were measured using the Modified Rankin Scale (mRS). For comparison, serum BDNF was measured in 50 healthy individuals. Results: BDNF levels were found to significantly increase during the phase with AR-based rehabilitation. The pattern of the sequentially measured BDNF levels was similar in the treated patients. Untreated patients had significantly lower BDNF levels at the endpoint. Conclusions: the fluctuations of BDNF levels are not consistently related to motor improvement but seem to react to active treatment. Without active rehabilitation treatment, BDNF tends to decrease.

Screening of brain-derived neurotrophic factor (BDNF) single nucleotide polymorphisms and plasma BDNF levels among Malaysian major depressive disorder patients.

BackgroundBrain-derived neurotrophic factor (BDNF) is a neurotrophin found in abundance in brain regions such as the hippocampus, cortex, cerebellum and basal forebrain. It has been associated with the risk of susceptibility to major depressive disorder (MDD). This study aimed to determine the association of three BDNF variants (rs6265, rs1048218 and rs1048220) with Malaysian MDD patients.MethodsThe correlation of these variants to the plasma BDNF level among Malaysian MDD patients was assessed. A total of 300 cases and 300 matched controls recruited from four public hospitals within the Klang Valley of Selangor State, Malaysia and matched for age, sex and ethnicity were screened for BDNF rs6265, rs1048218 and rs1048220 using high resolution melting (HRM).FindingsBDNF rs1048218 and BDNF rs1048220 were monomorphic and were excluded from further analysis. The distribution of the alleles and genotypes for BDNF rs6265 was in Hardy-Weinberg equilibrium for the controls (p = 0.13) but was in Hardy Weinberg disequilibrium for the cases (p = 0.011). Findings from this study indicated that having BDNF rs6265 in the Malaysian population increase the odds of developing MDD by 2.05 folds (95% CI = 1.48–3.65). Plasma from 206 cases and 206 controls were randomly selected to measure the BDNF level using enzyme-linked immunosorbent assay (ELISA). A significant decrease in the plasma BDNF level of the cases as compared to controls (p<0.0001) was observed. However, there was no evidence of the effect of the rs6265 genotypes on the BDNF level indicating a possible role of other factors in modulating the BDNF level that warrants further investigation.ConclusionThe study indicated that having the BDNF rs6265 allele (A) increase the risk of developing MDD in the Malaysian population suggesting a possible role of BDNF in the etiology of the disorder.

BDNF effects on dendritic spine morphology and hippocampal function.

Neurotrophins, including brain-derived neurotrophic factor (BDNF), are expressed in the hippocampus, as well as their precursors, the pro-neurotrophins. The neurotrophins signal through specific tyrosine kinase receptors and the low affinity receptor p75NTR. Moreover, the pro-neurotrophins are considered to be biologically active by signaling through specific receptors. The neurotrophins, especially BDNF, are involved in processes related to learning and memory. Furthermore, it is thought that BDNF also plays a crucial role in major depression. This points to a role of BDNF as a central regulator of neuronal plasticity within the postnatal hippocampus. Morphological correlates of neuronal plasticity are changes on the level of the dendritic spines and, at least in the dentate gyrus of the hippocampus, on the level of adult neurogenesis. Specific changes in dendritic spines as well as in adult hippocampal neurogenesis can be seen in the context of several forms of learning and memory, and it is known that depression is accompanied by declines in the rate of adult neurogenesis and in spine densities. The possible roles of BDNF in neuronal plasticity within the hippocampus are highlighted in this review by focusing on the morphological components of neuronal plasticity.

LOW SERUM BRAIN-DERIVED NEUROTROPHIC FACTOR BUT NOT BRAIN-DERIVED NEUROTROPHIC FACTOR GENE VAL66MET POLYMORPHISM IS ASSOCIATED WITH DIABETIC RETINOPATHY IN CHINESE TYPE 2 DIABETIC PATIENTS.

The aim of our research was to investigate the potential role of brain-derived neurotrophic factor (BDNF) in diabetic retinopathy (DR). Measurement of serum circulating levels of BDNF and analysis of polymorphism of BDNF gene (Val66Met) were applied and compared with diabetic patients without DR. From February 2014 and March 2015, all eligible patients with Type 2 diabetic mellitus at our hospital were consecutively recruited (N = 404). Their serum BDNF levels were detected by enzyme-linked immunosorbent assay. BDNF val66met polymorphism genotyping was conducted according to the laboratory's standard protocol. At baseline, demographic and clinical data were taken. The relationship of BDNF with DR was investigated with the use of logistic regression models. Receiver operating characteristic curves were used to test the overall accuracy of BDNF and other markers. Diabetic patients with DR and vision-threatening DR had significantly lower BDNF levels on admission (P < 0.0001 both). The BDNF genotyping results showed that there was no difference between the diabetic patients with DR and those without DR. Multivariate logistic regression analysis adjusted for common risk factors showed that serum BDNF levels were independent risk factors for DR (odds ratio = 0.86; 95% confidence interval [CI]: 0.80-0.92; P < 0.0001) and vision-threatening DR (odds ratio = 0.79; 95% CI: 0.75-0.85; P < 0.0001). Brain-derived neurotrophic factor improved the area under the receiver operating characteristic curve of the diabetes duration for DR from 0.69 (95% CI: 0.60-0.76) to 0.85 (95% CI: 0.79-0.90; P < 0.01) and for vision-threatening DR from 0.77 (95% CI: 0.67-0.87) to 0.86 (95% CI: 0.80-0.92; P < 0.01). The present study demonstrated that, rather than Val66Met polymorphism, decreased serum levels of BDNF were associated with DR and vision-threatening DR in Chinese Type 2 diabetic patients, suggesting a possible role of BDNF in the pathogenesis of DR complications.

BDNF pro-peptide: a novel synaptic modulator generated as an N-terminal fragment from the BDNF precursor by proteolytic processing

Most growth factors are initially synthesized as precursors and it was cleaved into bioactive mature domain and pro-domain. However, compared with the expression and function of bioactive mature domain, the biological role of the pro-domain is poorly understood. Unexpectedly, we found that the pro-domain (or pro-peptide) of brain-derived neurotrophic factor (BDNF), which is well-known neurotrophic factor in brain, has a potential ability to facilitate hippocampal long-term depression. Furthermore, a BDNF polymorphism Val66Met, which substitute valine into methionine at 66 amino acid, impacted the biological activity of the BDNF pro-peptide. We lastly discuss the possible roles of BDNF and its pro-peptide in the generation of neural stem cells and progress of ischemia.

Low brain-derived neurotrophic factor levels are associated with active disease and poor prognosis in childhood acute leukemia.

Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related receptor kinase B (TrkB) are involved in the maturation of B lymphocytes in the bone marrow (BM), promote cell differentiation in B-cell malignancies, and are associated with poor prognosis in adults with acute leukemia (AL). However, the role of BDNF in pediatric AL remains poorly understood. We carried out a cohort observational study to evaluate BDNF levels in BM or peripheral blood (PB) samples from children with AL. BM or PB samples were collected from 57 children and adolescents with acute lymphoid leukemia (ALL), 14 children and adolescents with acute myeloid leukemia (AML), and 44 healthy individuals (HI) of the same age range. BDNF levels at diagnosis in AL patients were significantly lower when compared to HI. Samples from patients in complete remission from disease had higher levels of BDNF compared to those obtained from patients with malignant cells. Moreover, BDNF levels at diagnosis in patients who died were significantly lower compared to those found in survivors. These findings provide the first evidence for a possible role of BDNF as a marker of active disease and poor prognosis in pediatric AL.

Elevated Brain-Derived Neurotrophic Factor Correlates Negatively with Severity and Duration of Major Depressive Episodes

Major depressive disorder is a neuropsychiatric condition associated with neurochemical changes that alter levels of neurotrophins. We aimed to measure serum levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in patients experiencing their first episode of major depression and to examine those levels in relation to the severity and duration of the depressive episode. We recruited 85 participants: 44 drug-free patients with major depression (35 women, 9 men) and 41 healthy controls (32 women, 9 men). We used the Hamilton Rating Scale for Depression to assess the severity of the patients' depression. We assessed the controls' mental health according to Diagnostic and Statistical Manual of Mental Disorders, 4th ed, criteria. To assess all participants' stress levels, we used the Holmes and Rahe stress scale. We measured all participants' serum BDNF and NGF levels via enzyme-linked immunosorbent assay. The mean stress score was significantly higher in the patients than the controls (P=0.03). The patients had higher serum BDNF than the controls (P=0.001), but similar NGF levels. BDNF levels correlated negatively with symptom severity (r=-0.33, P=0.03) and duration (r=-0.2, P=0.06). NGF levels did not correlate with stress or with severity or duration of depressive episode. These findings suggest that an elevated serum BDNF level may contribute to the pathophysiology of major depressive disorder. The findings also indicate a possible role for BDNF in altering the clinical course of the condition.

Contribution of capsaicin-sensitive primary afferents to mechanical hyperalgesia induced by ventral root transection in rats: the possible role of BDNF

Objective: A recent study showed that brain-derived neurotrophic factor (BDNF) may play a role in the development of the neuropathic pain resulting from injury to motor efferent fibres, such as that in the ventral root transection (VRT) model. Capsaicin stimulation of afferent fibres was also shown to result in the release of BDNF into the spinal cord. Here, the effects of ablation of capsaicin-sensitive primary afferents (CSPAs) by local application of capsaicin on the sciatic nerve on VRT-induced mechanical hyperalgesia were observed.Methods: The paw withdrawal mechanical threshold (PWMT) was measured before and then 1 and 3 days and 1, 2, 3, 4 and 6 weeks after VRT.Results: The results showed that local application of capsaicin significantly inhibited the decrease in the PWMT induced by VRT, suggesting the inhibitory effect of locally delivered capsaicin. Furthermore, intrathecal administration of exogenous BDNF not only produced mechanical hyperalgesia but also significantly blocked the inhibitory effect of capsaicin.Conclusion: Taken together, the results of this study suggest that CSPA fibres may contribute to mechanical hyperalgesia in the VRT model.

Low plasma levels of brain derived neurotrophic factor are potential risk factors for diabetic retinopathy in Chinese type 2 diabetic patients

Previous studies suggested that neurotrophins play a role in the diabetic retinopathy (DR). We therefore evaluated the role of plasma brain derived neurotrophic factor (BDNF) levels in Chinese type 2 diabetic patients with and without diabetic retinopathy (DR). Plasma levels of BDNF were determined in type 2 diabetic patients (N=344). At baseline, the demographical and clinical data were taken. Multivariate analyses were performed using logistic regression models. Receiver operating characteristic curves (ROC) was used to test the overall predict accuracy of BDNF and other markers. Diabetic patients with DR and vision-threatening diabetic retinopathy (VTDR) had significantly lower BDNF levels on admission (P<0.0001 both). BDNF improved the area under the receiver operating characteristic curve of the diabetes duration for DR from 0.76 (95% confidence interval [CI], 0.71–0.82) to 0.89 (95% CI, 0.82–0.95; P<0.01) and for VDTR from 0.84 (95% CI, 0.78–0.92) to 0.95 (95% CI, 0.90–0.98; P<0.01). Multivariate logistic regression analysis adjusted for common risk factors showed that plasma BDNF levels≤12.4 ng/mL(1rd quartiles) was an independent marker of DR (OR=3.92; 95%CI: 2.31–6.56) and VTDR (OR=4.88; 95%CI: 2.21–9.30). The present study demonstrated that decreased plasma levels of BDNF were independent markers for DR and VDTR in Chinese type 2 diabetic patients, suggesting a possible role of BDNF in the pathogenesis of DR complications.

Differential Regulation of Brain-Derived Neurotrophic Factor in Term and Preterm Preeclampsia

Our earlier studies in preeclampsia (PE) suggest a causal relationship between altered angiogenic factors and birth outcomes. Recent studies suggest that brain-derived neurotrophic factor (BDNF) can stimulate angiogenesis. The present study examines the levels of maternal and cord BDNF in women with PE (n = 106; full term [n = 60] and preterm [n = 46]) and normotensive women (n = 95; control) delivering at term. Maternal BDNF levels were lower (P < .05) in women with PE when compared to normotensive women. Cord BDNF levels were higher (P < .01) in women with PE delivering at term, while it was lower (P < .01) in women delivering preterm. Maternal BDNF levels were negatively associated with systolic and diastolic blood pressure (P < .01 for both). Our data for the first time suggest a possible role for BDNF in the pathophysiology of PE. Differential regulation of cord BDNF levels in preterm PE suggests a need to follow-up children to assess the neurodevelopmental effects in later life.

Diabetes Impairs Synaptic Plasticity in the Superior Cervical Ganglion: Possible Role for BDNF and Oxidative Stress

The majority of diabetics develop serious disorders of the autonomic nervous system; however, there is no clear understanding on the causes of these complications. In this study, we examined the effect of streptozocin (STZ)-induced diabetes on activity-dependent synaptic plasticity, associated levels of brain-derived neurotrophic factor (BDNF) and antioxidant biomarkers in the rat sympathetic superior cervical ganglion. Diabetes (STZ-induced) was achieved by a single intraperitoneal injection of streptozocin (55mg/kg).Compound action potentials were recorded from isolated ganglia before (basal) and after repetitive stimulation, or trains of paired pulses to express ganglionic long-term potentiation (gLTP) or long-term depression (gLTD). The input/output curves of ganglia from STZ-treated animals showed a marked rightward shift along most stimulus intensities, compared to those of ganglia from control animals, indicating impaired basal synaptic transmission in ganglia from STZ-induced diabetic animals. Repetitive stimulation induced robust gLTP and gLTD in ganglia isolated from control animals; the same protocols failed to induce gLTP or gLTD in ganglia from STZ-induced diabetic animals, indicating impairment of activity-dependent synaptic plasticity in these animals. Molecular analysis revealed significant reduction in the levels of BDNF and the ratio of glutathione/oxidized glutathione. Additionally, the activity of glutathione peroxidase, glutathione reductase, catalase, and the levels of thiobarbituric acid-reactive substances were increased in ganglia from STZ-treated animals. In conclusion, impaired basal synaptic transmission and synaptic plasticity are associated with reduced BDNF and altered oxidative stress biomarkers in the sympathetic ganglia from STZ-induced diabetic animals, suggesting a possible correlation of these factors with the manifestations of STZ-induced diabetes in the peripheral nervous system.