Research Progress on Brain-Derived Neurotrophic Factor (BDNF) in the Sequelae of Stroke

The research progress of brain-derived neurotrophic factor (BDNF) in the treatment of sequelae of stroke is an important topic. Stroke is among the diseases with the highest mortality and disability rates among the elderly in China. BDNF plays an important role in the development and functional maintenance of the nervous system. In recent years, the application value of BDNF in rehabilitation therapy has gradually received attention. This study has adopted a systematic literature review method, searched Chinese and English databases, screened relevant studies, and conducted data extraction and quality evaluation. This review systematically introduced the research progress of BDNF in the correlation with post-stroke sequelae, with special attention to its application in post-stroke depression, motor dysfunction, and cognitive dysfunction. The results showed that a decrease in BDNF levels is closely related to the exacerbation of depressive symptoms, limited recovery of motor dysfunction, and the occurrence of cognitive dysfunction. BDNF, as a key neurobiological factor, has shown significant potential in the rehabilitation treatment of stroke. By exploring the potential of BDNF as a therapeutic target to prevent and treat sequelae of ischemic stroke, the current research bottlenecks, and the development trends of future treatment strategies.

Brain-derived neurotrophic factor induces neuron-like cellular differentiation of mesenchymal stem cells derived from human umbilical cord blood cells in vitro

Human umbilical cord blood was collected from full-term deliveries scheduled for cesarean section. Mononuclear cells were isolated, amplified and induced as mesenchymal stem cells. Isolated mesenchymal stem cells tested positive for the marker CD29, CD44 and CD105 and negative for typical hematopoietic and endothelial markers. Following treatment with neural induction medium containing brain-derived neurotrophic factor for 7 days, the adherent cells exhibited neuron-like cellular morphology. Immunohistochemical staining and reverse transcription-PCR revealed that the induced mesenchymal stem cells expressed the markers for neuron-specific enolase and neurofilament. The results demonstrated that human umbilical cord blood-derived mesenchymal stem cells can differentiate into neuron-like cells induced by brain-derived neurotrophic factor in vitro.

Human umbilical cord blood stem cells and brainderived neurotrophic factor for optic nerve injury: a biomechanical evaluation

Treatment for optic nerve injury by brain-derived neurotrophic factor or the transplantation of human umbilical cord blood stem cells has gained progress, but analysis by biomechanical indicators is rare. Rabbit models of optic nerve injury were established by a clamp. At 7 days after injury, the vitreous body received a one-time injection of 50 μg brain-derived neurotrophic factor or 1 × 10^6 human umbilical cord blood stem cells. After 30 days, the maximum load, maximum stress, maximum strain, elastic limit load, elastic limit stress, and elastic limit strain had clearly improved in rabbit models of optical nerve injury after treatment with brain-derived neurotrophic factor or human umbilical cord blood stem cells. The damage to the ultrastructure of the optic nerve had also been reduced. These findings suggest that human umbilical cord blood stem cells and brain-derived neurotrophic factor effectively repair the injured optical nerve, improve biomechanical properties, and contribute to the recovery after injury.

Human umbilical cord blood-derived stem cells and brain-derived neurotrophic factor protect injured optic nerve:viscoelasticity characterization

The optic nerve is a viscoelastic solid-like biomaterial.Its normal stress relaxation and creep properties enable the nerve to resist constant strain and protect it from injury.We hypothesized that stress relaxation and creep properties of the optic nerve change after injury.Moreover,human brain-derived neurotrophic factor or umbilical cord blood-derived stem cells may restore these changes to normal.To validate this hypothesis,a rabbit model of optic nerve injury was established using a clamp approach.At 7 days after injury,the vitreous body received a one-time injection of 50 μg human brain-derived neurotrophic factor or 1 × 106 human umbilical cord blood-derived stem cells.At 30 days after injury,stress relaxation and creep properties of the optic nerve that received treatment had recovered greatly,with pathological changes in the injured optic nerve also noticeably improved.These results suggest that human brain-derived neurotrophic factor or umbilical cord blood-derived stem cell intervention promotes viscoelasticity recovery of injured optic nerves,and thereby contributes to nerve recovery.

Adenovirus-mediated human brain-derived neurotrophic factor gene-modified bone marrow mesenchymal stem cell transplantation for spinal cord injury

Rat bone marrow mesenchymal stem cells expressing brain-derived neurotrophic factor were successfully obtained using a gene transfection method, then intravenously transplanted into rats with spinal cord injury. At 1,3, and 5 weeks after transplantation, the expression of brain-derived neurotrophic factor and neurofilament-200 was upregulated in the injured spinal cord, spinal cord injury was alleviated, and Basso-Beattie-Bresnahan scores of hindlimb motor function were significantly increased. This evidence suggested that intravenous transplantation of adenovirus- mediated brain-derived neurotrophic factor gene-modified rat bone marrow mesenchymal stem cells could play a dual role, simultaneously providing neural stem cells and neurotrophic factors.

EXPRESSING HUMAN MATURED BRAIN-DERIVED NEUROTROPHIC FACTOR GENE IN E.Coli AND DETERMINING ITS BIOACTIVITY

Objective Expressing the human matured brain-derived neurotrophic factor (mBDNF) gene in E. Coli and determining its bioactivity. Methods The resulting gene of mBDNF was subcloned into the EcoRI-BamHI site or the expression vector plasmid pBV220. The ligation products were used to transform the competent E. Coli DH5a. The proteins or mBDNF were experessed by temperature inducing. The expression products were dealed with solubilizing inclusion bodies and refolding protein. It was introduced into the embryonic chicken DRG to test whether the expressed mBDNF is a biologically active protein. Results The recombinant plasmid pBV/mBDNF was success- fully constructed. By temperature inducing, under the control of the bacteriophage λPL promoter, the experessed mBDNF protein was a 14Kd non-fusion protein,which existed in E. Coli as inclusion bodies. The size or expressed mBDNF is identical to the prediction. Bioactivity of the products was proved that it could support the cell survival and neurite growth in the primary cultures of embryonic 8-day-old chicken DRG neurons as compared to control. Conclusion Tke mBDNF gene can be expressed bioactively in E. Coli.

Construction of a plasmid for human brain-derived neurotrophic factor and its effect on retinal pigment epithelial cell viability

Several studies have investigated the protective functions of brain-derived neurotrophic factor（BDNF） in retinitis pigmentosa. However, a BDNF-based therapy for retinitis pigmentosa is not yet available. To develop an efficient treatment for fundus disease, an eukaryotic expression plasmid was generated and used to transfect human 293 T cells to assess the expression and bioactivity of BDNF on acute retinal pigment epithelial-19（ARPE-19） cells, a human retinal epithelial cell line. After 96 hours of co-culture in a Transwell chamber, ARPE-19 cells exposed to BDNF secreted by 293 T cells were more viable than ARPE-19 cells not exposed to secreted BDNF. Western blot assay showed that Bax levels were downregulated and that Bcl-2 levels were upregulated in human ARPE-19 cells exposed to BDNF. Furthermore, 293 T cells transfected with the BDNF gene steadily secreted the protein. The powerful anti-apoptotic function of this BDNF may be useful for the treatment of retinitis pigmentosa and other retinal degenerative diseases.

Are the changes in the peripheral brain-derived neurotrophic factor levels due to platelet activation?

Brain-derived neurotrophic factor(BDNF) plays an important role in central nervous system development, neurogenesis and neuronal plasticity. BDNF is also expressed in several non-neuronal tissues, and it could play an important role in other processes, such as cancer, angiogenesis, etc. Platelets are the major source of peripheral BDNF. However, platelets also contain high amounts of serotonin; they express specific surface receptors during activation, and a multitude of pro-inflammatory and immunomodulatory bioactive compounds are secreted from the granules. Until recently, there was insufficient knowledge regarding the relationship between BDNF and platelets. Recent studies showed that BDNF is present in two distinct pools in platelets, in α-granules and in the cytoplasm, and only the BDNF in the granules is secreted following stimulation, representing 30% of the total BDNF in platelets. BDNF has an important role in the pathophysiology of depression. Low levels of serum BDNF have been described in patients with major depressive disorder, and BDNF levels increased with chronic antidepressant treatment. Interestingly, there is an association between depression and platelet function. This review analyzed studies that evaluated the relationship between BDNF and platelet activation and the effect of treatments on both parameters. Only a few studies consider this possible confounding factor, and it could be very important in diseases such as depression, which show changes in both parameters.

Relationship between brain—derived neurotrophic factor and cognitive function of obstructive sleep apnea/hypopnea syndrome patients

Objective:To determine the relationship between the blood serum brain-derived neurotrophic factor（BDNF） level and cognitive function deterioration in patients with obstructive sleep apnea/ hypopnea syndrome（OSAHS）,and to explore the possible mechanism of cognitive impairment. Methods:Twenty-eight male OSAHS patients and 14 normal males（as controls） were enrolled in the study.Polysomnography and the Montreal cognitive assessment（MoCA） were conducted. The blood serum BDNF levels were measured using ELISA.Results:The OSAHS group had significantly decreased blood serum BDNF levels compared with the control group（t=-10.912, P=0.000）.The blood serum BDNF level of the subjects was significantly positively associated with the MoCA score（r=0.544,P=0.000）,significantly negatively associated with the apneahypopnea index（AHI） and shallow sleep（S1+S2）（AHI:r=-0.607,P=0.000;S1+S2:r =-0.768,P= 0.000）,and significantly positively associated with the lowest SaO2（LSO）,slow wave sleep（S3+S4）, and rapid eye movement sleep（REM）（LSO:r=0.566,P = 0.000;S3+S4:r=0.778,P=0.000;REM: r=0.575,P=0.000）.Conclusions:OSAHS patients have significantly decreased blood serum BDNF levels compared with the control.Nocturnal hypoxia as well as the deprivation of slow wave sleep and REM may lead to the decreased serum BDNF level of OSAHS patients.This decreased blood serum BDNF level may contribute to the cognitive impairment in OSAHS.

Increased expression of brain-derived neurotrophic factor is correlated with visceral hypersensitivity in patients with diarrheapredominant irritable bowel syndrome

BACKGROUND Visceral hypersensitivity is considered to play a vital role in the pathogenesis of irritable bowel syndrome(IBS). Neurotrophins have drawn much attention in IBS recently. Brain-derived neurotrophic factor(BDNF) was found to mediate visceral hypersensitivity via facilitating sensory nerve growth in pre-clinical studies. We hypothesized that BDNF might play a role in the pathogenesis of diarrhea-predominant IBS(IBS-D).AIM To investigate BDNF levels in IBS-D patients and its role in IBS-D pathophysiology.METHODS Thirty-one IBS-D patients meeting the Rome IV diagnostic criteria and 20 ageand sex-matched healthy controls were recruited. Clinical and psychological assessments were first conducted using standardized questionnaires. Visceral sensitivity to rectal distension was tested using a high-resolution manometry system. Colonoscopic examination was performed and four mucosal pinch biopsies were taken from the rectosigmoid junction. Mucosal BDNF expression and nerve fiber density were analyzed using immunohistochemistry. Mucosal BDNF mRNA levels were quantified by quantitative real-time polymerase chain reaction. Correlations between these parameters were examined.RESULTS The patients had a higher anxiety score [median(interquartile range), 6.0(2.0-10.0) vs 3.0(1.0-4.0), P = 0.003] and visceral sensitivity index score [54.0(44.0-61.0)vs 21.0(17.3-30.0), P < 0.001] than controls. The defecating sensation threshold[60.0(44.0-80.0) vs 80.0(61.0-100.0), P = 0.009], maximum tolerable threshold[103.0(90.0-128.0) vs 182.0(142.5-209.3), P < 0.001] and rectoanal inhibitory reflex threshold [30.0(20.0-30.0) vs 30.0(30.0-47.5), P = 0.032] were significantly lower in IBS-D patients. Intestinal mucosal BDNF protein [3.46 E-2(3.06 E-2-4.44 E-2) vs3.07 E-2(2.91 E-2-3.48 E-2), P = 0.031] and mRNA [1.57(1.31-2.61) vs 1.09(0.74-1.42), P = 0.001] expression and nerve fiber density [4.12 E-2(3.07 E-2-7.46 E-2) vs1.98 E-2(1.21 E-2-4.25 E-2), P = 0.002] were significantly elevated in the patients.Increased BDNF expression was positively correlated with abdominal pain and disease severity and negatively correlated with visceral sensitivity parameters.CONCLUSION Elevated mucosal BDNF may participate in the pathogenesis of IBS-D via facilitating mucosal nerve growth and increasing visceral sensitivity.

New insight in expression, transport, and secretion of brain-derived neurotrophic factor: Implications in brainrelated diseases

Brain-derived neurotrophic factor(BDNF) attracts increasing attention from both research and clinical fields because of its important functions in the central nervous system. An adequate amount of BDNF is critical to develop and maintain normal neuronal circuits in the brain. Given that loss of BDNF function has beenreported in the brains of patients with neurodegenerative or psychiatric diseases, understanding basic properties of BDNF and associated intracellular processes is imperative. In this review, we revisit the gene structure, transcription, translation, transport and secretion mechanisms of BDNF. We also introduce implications of BDNF in several brain-related diseases including Alzheimer's disease, Huntington's disease, depression and schizophrenia.

Effects of “Nourishing Liver and Kidney” Acupuncture Therapy on Expression of Brain Derived Neurotrophic Factor and Synaptophysin after Cerebral Ischemia Reperfusion in Rats

The aim of the present study was to investigate the effect of ＂nourishing liver and kidney＂ acupuncture therapy on motor and cognitive deficits,and the underlying mechanism following cerebral ischemia-reperfusion（I/R） via increasing the expression of brain derived neurotrophic factor（BDNF） and synaptophysin（SYN） in the hippocampus.Healthy adult male SD rats were randomly divided into sham operation group（n=51）,model group（n=51）,acupuncture group（n=51） and acupuncture control group（n=51）.The middle cerebral I/R model was established.Acupunctures were performed in the acupuncture group and acupuncture control group at acupoints of Taixi（K103）,Taichong（ST09） of both sides,for 30 min once daily every morning.The animals in the sham operation group and model group were conventionally fed in the cage,without any intervention therapy.The rats of each group were assessed with modified neurological severity scores（m NSS）.The expression of BDNF and SYN in the hippocampus was detected by immunohistochemical SP method and the synaptic structure in hippocampus area was assessed morphologically and quantitatively at the 3rd,7th and 14 th day.The Morris water Maze（MWM） test was used to evaluate the rats＇ learning and memory abilities on the 15 th day after acupuncture.The animals in the acupuncture control group and sham operation group presented no neurological deficit.In the acupuncture group,the nerve functional recovery was significantly better than that in the model group at the 7th and 14 th day after modeling.The average MWM escape latency in the acupuncture group was shorter than that in the model group at the 3rd,4th and 5th day.The number of crossings of the platform quadrant in the acupuncture group was significantly more than that in the model group.At the each time point,the expression levels of BDNF and SYN in the hippocampal regions increased significantly in the model group as compared with the sham operation group and the acupuncture control group.In the acupuncture group,the expression levels of BDNF at the 7th and 14 th day increased more significantly than those in the model group.In the acupuncture group,the expression levels of SYN at the each time point increased more significantly than those in the model group.The post-synaptic density（PSD） was significantly increased and the synapse cleft width was narrowed in the acupuncture group as compared with other groups.The synaptic curvatures were improved obviously in the acupuncture group in contrast to the model group.It was concluded that the ＂nourishing liver and kidney＂ acupuncture therapy has positive effects on behavioral recovery,as well as learning and memory abilities,probably by promoting the expression of BDNF and SYN,and synaptic structure reconstruction in the ipsilateral hippocampus after I/R in rats.The ＂nourishing liver and kidney＂ acupuncture therapy can promote the functional recovery in rats after cerebral ischemia injury.

Role of brain-derived neurotrophic factor during the regenerative response after traumatic brain injury in adult zebrafish

Several mammalian animal models of traumatic brain injury have been used, mostly rodents. However, reparative mechanisms in mammalian brain are very limited, and newly formed neurons do not survive for long time. The brain of adult zebrafish, a teleost fish widely used as vertebrate model, possesses high regenerative properties after injury due to the presence of numerous stem cells niches. The ventricular lining of the zebrafish dorsal telencephalon is the most studied neuronal stem cell niche because its dorso-lateral zone is considered the equivalent to the hippocampus of mammals which contains one of the two constitutive neurogenic niches of mammals. To mimic TBI, stab wound in the dorso-lateral telencephalon of zebrafish was used in studies devoted to fish regenerative properties. Brain-derived neurotrophic factor, which is known to play key roles in the repair process after traumatic brain lesions, persists around the lesioned area of injured telencephalon of adult zebrafish. These results are extensively compared to reparative processes in rodent brain. Considering the complete repair of the damaged area in fish, it could be tempting to consider brain-derived neurotrophic factor as a factor contributing to create a permissive environment that enables the establishment of new neuronal population in damaged brain.

Brain-derived neurotrophic factor mediates macrophage migration inhibitory factor to protect neurons against oxygen-glucose deprivation

Macrophage migration inhibitory factor(MIF)is a chemokine that plays an essential role in immune system function.Previous studies suggested that MIF protects neurons in ischemic conditions.However,few studies are reported on the role of MIF in neurological recovery after ischemic stroke.The purpose of this study is to identify the molecular mechanism of neuroprotection mediated by MIF.Human neuroblastoma cells were incubated in Dulbecco’s modified Eagle’s medium under oxygen-glucose deprivation(OGD)for 4 hours and then returned to normal aerobic environment for reperfusion(OGD/R).30 ng/mL MIF recombinant(30 ng/mL)or ISO-1(MIF antagonist;50μM)was administered to human neuroblastoma cells.Then cell cultures were assigned to one of four groups:control,OGD/R,OGD/R with MIF,OGD/R with ISO-1.Cell viability was analyzed using WST-1 assay.Expression levels of brain-derived neurotrophic factor(BDNF),microtubule-associated protein 2(MAP2),Caspase-3,Bcl2,and Bax were detected by western blot assay and immunocytochemistry in each group to measure apoptotic activity.WST-1 assay results revealed that compared to the OGD/R group,cell survival rate was significantly higher in the OGD/R with MIF group and lower in the OGD/R with ISO-1 group.Western blot assay and immunocytochemistry results revealed that expression levels of BDNF,Bcl2,and MAP2 were significantly higher,and expression levels of Caspase-3 and Bax were significantly lower in the MIF group than in the OGD/R group.Expression levels of BDNF,Bcl2,and MAP2 were significantly lower,and expression levels of Caspase-3 and Bax were significantly higher in the ISO-1 group than in the OGD/R group.MIF administration promoted neuronal cell survival and induced high expression levels of BDNF,MAP2,and Bcl2(anti-apoptosis)and low expression levels of Caspase-3 and Bax(pro-apoptosis)in an OGD/R model.These results suggest that MIF administration is effective for inducing expression of BDNF and leads to neuroprotection of neuronal cells against hypoxic injury.

Three important components in the regeneration of the cavernous nerve： brain-derived neurotrophic factor, vascular endothelial growth factor and the JAK/STAT signaling pathway

Retroperitoneal operations, such as radical prostatectomy, often damage the cavernous nerve, resulting in a high incidence of erectile dysfunction. Although improved nerve-sparing techniques have reduced the incidence of nerve injury, and the administration of phosphodiesterase type 5 inhibitors has revolutionized the treatment of erectile dysfunction, this problem remains a considerable challenge. In recent years, scientists have focused on brain-derived neurotrophic factor and vascular endothelial growth factor in the treatment of cavernous nerve injury in rat models. Results showed that both compounds were capable of enhancing the regeneration of the cavernous nerve and that activation of the Janus kinase （JAK）/signal transducer and activator of transcription （STAT） pathway played a major role in the process.

Effect of Transcranial Magnetic Stimulation on the Expression of c-Fos and Brain-derived Neurotrophic Factor of the Cerebral Cortex in Rats with Cerebral Infarct

The effect of transcranial magnetic stimulation （TMS） on the neurological functional recovery and expression of c-Fos and brain-derived neurotrophic factor （BDNF） of the cerebral cortex in rats with cerebral infarction was investigated. Cerebral infarction models were established by using left middle cerebral artery occlusion （MCAO） and were randomly divided into a model group （n=40） and a TMS group （n=40）. TMS treatment （2 times per day, 30 pulses per time） with a frequency of 0.5 Hz and magnetic field intensity of 1.33 Tesla was carried out in TMS group after MCAO. Modified neurological severity score （NSS） were recorded before and 1, 7, 14, 21, and 28 day（s） after MCAO. The expression of c-Fos and BDNF was immunohistochemically detected 1, 7, 14, 21, and 28 day（s） after infarction respectively. Our results showed that a significant recovery of NSS （P〈0.05） was found in animals treated by TMS on day 7, 14, 21, and 28 as compared with the animals in the model group. The positive expression of c-Fos and BDNF was detected in the cortex surrounding the infarction areas, while the expression of c-Fos and BDNF increased significantly in TMS treatment group in comparison with those in model group 7, 14, 21, and 28 days （P〈0.05） and 7 14, 21 days （P〈0.01） after infarction, respectively. It is concluded that TMS has therapeutic effect on cerebral infarction and this may have something to do with TMS＇s ability to promote the expression of c-Fos and BDNF of the cerebral cortex in rats with cerebral infarction.

Role of brain-derived neurotrophic factor and neuronal nitric oxide synthase in stress-induced depression

BACKGROUND： Accumulated evidence indicates an important role for hippocampal dendrite atrophy in development of depression, while brain-derived neurotrophic factor （BDNF） participates in hippocampal dendrite growth. OBJECTIVE： To discuss the role of BDNF and neuronal nitric oxide synthase （nNOS） in chronic and unpredictable stress-induced depression and the pathogenesis of depression. DESIGN, TIME AND SETTING： Randomized, controlled animal experiment. The experiment was carded out from October 2006 to May 2007 at the Department of Animal Physiology, College of Life Science, Shaanxi Normal University. MATERIALS： Thirty-seven male Sprague-Dawley rats weighing 250-300 g at the beginning of the experiment were obtained from Shaanxi Provincial Institute of Traditional Chinese Medicine （Xi＇an, China）. BDNF antibody and nNOS antibody were provided by Santa Cruz （USA）. K252a （BDNF inhibitor） and 7-NI （nNOS inhibitor） were provided by Sigma （USA）. METHODS： Animals were randomly divided into five groups： Control group, chronic unpredicted mild stress （CUMS） group, K252a group, K252a＋7-NI group and 7-NI＋CUMS group. While the Control, K252a and K252a＋7-NI groups of rats not subjected to stress had free access to food and water, other groups of rats were subjected to nine stressors randomly applied for 21 days, with each stressor applied 2-3 times. On days 1, 7, 14 and 21 during CUMS, rats received microinjection of 1 μL of physiological saline in the Control and CUMS groups, 1 ~ L of K252a in the K252a group, 1 μL of K252a and 7-NI in the K252a＋7-NI group, and 1 μL of 7-NI in the 7-NI＋CUMS group. We observed a variety of alterations in sucrose preference, body weight change, open field test and forced swimming test, and observed the expression of BDNF and nNOS in rat hippocampus by immunohistochemistry; MAIN OUTCOME MEASURES： ① A variety.of behavioral alterations of rats; ② The expression of BDNF and nNOS in rat hippocampus. RESULTS： Compared with the Control group, the behavior of the CUMS rats was significantly depressed, the expression of BDNF decreased （P 〈 0.01） but the expression of nNOS increased （P 〈 0.01）. The behavior of rats given intra-hippocampal injection of BDNF inhibitor was significantly depressed and the expression of nNOS was significantly increased （P 〈 0.01）. Intra-hippocampal injections of an nNOS inhibitor reversed the depression-like behavioral changes induced by CUMS or intra-hippocampal injection of BDNF inhibitor. CONCLUSION： CUMS induced a decrease in expression of BDNF and an increase in expression of NO in the hippocampus, which may lead to depression.

Effects of lateral ventricular transplantation of bone marrow-derived mesenchymal stem cells modified with brain-derived neurotrophic factor gene on cognition in a rat model of Alzheimer's disease

In the present study, transplantation of bone marrow-derived mesenchymal stem cells modified with brain-derived neurotrophic factor gene into the lateral ventricle of a rat model of Alzheimer＇s disease, resulted in significant attenuation of nerve cell damage in the hippocampal CA1 region. Furthermore, brain-derived neurotrophic factor and tyrosine kinase B mRNA and protein levels were significantly increased, and learning and memory were significantly improved. Results indicate that transplantation of bone marrow-derived mesenchymal stem cells modified with brain-derived neurotrophic factor gene can significantly improve cognitive function in a rat model of Alzheimer＇s disease, possibly by increasing the levels of brain-derived neurotrophic factor and tyrosine kinase B in the hippocampus.

Post-traumatic stress disorder risk and brain-derived neurotrophic factor Val66Met

Brain-derived neurotrophic factor(BDNF), which regulates neuronal survival, growth differentiation, and synapse formation, is known to be associated with depression and post-traumatic stress disorder(PTSD). However, the molecular mechanism for those mental disorders remains unknown. Studies have shown that BDNF is associated with PTSD risk and exaggerated startle reaction(a major arousal manifestation of PTSD) in United States military service members who were deployed during the wars in Iraq and Afghanistan. The frequency of the Met/Met in BDNF gene was greater among those with PTSD than those without PTSD. Among individuals who experienced fewer lifetime stressful events, the Met carriers have significantly higher total and startle scores on the PTSD Checklist than the Val/Val carriers. In addition, subjects with PTSD showed higher levels of BDNF in their peripheral blood plasma than the non-probable-PTSD controls. Increased BDNF levels and startle response were observed in both blood plasma and brain hippocampus by inescapable tail shock in rats. In this paper, we reviewed these data to discuss BDNF as a potential biomarker for PTSD risk and its possible roles in the onset of PTSD.

Brain-derived neurotrophic factor plasma levels and premature cognitive impairment/dementia in type 2 diabetes

AIM To assess the relationship of brain-derived neurotrophic factor(BDNF) with cognitive impairment in patients with type 2 diabetes. METHODS The study included 40 patients with diabetes mellitus type 2(DM2), 37 patients with chronic kidney disease in hem dialysis hemodialysis therapy(HD) and 40 healthy subjects. BDNF in serum was quantified by ELISA. The Folstein Mini-Mental State Examination was used to evaluate cognitive impairment.RESULTS The patients with DM2 and the patients in HD were categorized into two groups, with cognitive impairment and without cognitive impairment. The levels of BDNF showed significant differences between patients with DM2(43.78 ± 9.05 vs 31.55 ± 10.24, P = 0.005). There were no differences between patients in HD(11.39 ± 8.87 vs 11.11 ± 10.64 P = 0.77); interestingly, ferritin levels were higher in patients with cognitive impairment(1564 ± 1335 vs 664 ± 484 P = 0.001). The comparison of BDNF values, using a Kruskal Wallis test, between patients with DM2, in HD and healthy controls showed statistical differences(P < 0.001).CONCLUSION Low levels of BDNF are associated with cognitive impairment in patients with DM2. The decrease of BDNF occurs early and progressively in patients in HD.