Expression Levels Of Brain-derived Neurotrophic Factor Research Articles

Prenatal stress differentially alters brain-derived neurotrophic factor expression and signaling across rat strains

Psychiatric illness and anxiety disorders have strong neurodevelopmental components. Environmental insults such as prenatal exposure to stress and genetic differences in stress responses may affect brain development. A rat model of random variable prenatal stress was used to study the expression and processing of hippocampal brain-derived neurotrophic factor (BDNF) in the offspring of the stressed rat dams. To account for unknown genetic influences that may play a role in the outcome of this prenatal stress paradigm, three different rat strains with known differences in stress responsivity were studied: Fischer, Sprague-Dawley, and Lewis rats (n=132). Multiple disparities in mRNA expression levels of BDNF, and transcripts related to its processing and signaling were found in the three strains. Of the numerous splice variants transcribed from the BDNF gene, the transcript containing BDNF exon VI was most aberrant in the prenatally stressed animals. Protein levels of both uncleaved proBDNF and mature BDNF were also altered, as was intra-cellular signaling by phosphorylation of the neurotrophic tyrosine kinase receptor type 2 (NTRK2, TrkB) and mitogen-activated protein kinase (Erk 1/2). Changes were not only dependent on prenatal stress, but were also strain dependent, demonstrating the importance of genetic background. BDNF signaling provides both positive neurotrophic support for neurons and negative apoptotic effects, both of which may contribute to behavioral or neurochemical outcomes after prenatal exposure to stress. Differential processing of BDNF after prenatal stress in the three rat strains has implications for human subjects where genetic differences may protect or exacerbate the effects of an environmental stressor during fetal development.

Electrical stimulation promotes BDNF expression in spinal cord neurons through Ca(2+)- and Erk-dependent signaling pathways.

Brief electrical stimulation has been shown to be effective in promoting neuronal regeneration following peripheral nerve injury. These effects are thought to be mediated largely by the upregulation of the expression of brain-derived neurotrophic factor (BDNF) in spinal cord neurons. However, the molecular mechanisms by which electrical stimulation can promote BDNF expression are not known. The mechanism involved in BDNF expression after electrical stimulation was explored in this study. Immunohistochemistry and Western blotting were used to test BDNF expression. Confocal microscopy was utilized to study intracellular Ca(2+) volume. Immunohistochemistry and Western blotting confirmed that brief electrical stimulation increased BDNF expression in spinal cord neurons both in vivo and in vitro. Treatment of cultured neurons with nifedipine, an inhibitor of voltage-gated calcium channels, significantly reduced the BDNF increase produced by electrical stimulation, and an inhibitor of Erk completely abolished the effect of electrical stimulation. Levels of BDNF expression in the presence of the Erk inhibitor were lower that in unstimulated and untreated controls, indicating that Erk activation is required to maintain baseline levels of BDNF. Confocal microscopy using a Ca(2+)-sensitive fluorochrome revealed that electrical stimulation is accompanied by an increase in intracellular Ca(2+) levels; the increase was partly blocked by nifedipine. These findings argue that electrical stimulation increases BDNF expression in spinal cord neurons by activating a Ca(2+)- and Erk-dependent signaling pathways.

Effect of brain-derived neurotrophic factor on environmental nutrition and neural differentiation of the transplanted stem cells under hypothermia

Objective To study the effect of brain-derived neurotrophic factor （BDNF） on the environmental nutrition and neural differentiation of the transplanted stem cells under hypothermia.Methods The BDNF gene mediated by liposome was transfected into 293T cell line, and ELISA assay was applied to find the peak time of BDNF expression. When BDNF was highly expressed, the supernatant was collected for establishment of SD rat models of brain injury. The rats were divided into Group A （stem cell transplantation group） and Group B （stem cell transplantation and BDNF group）. Rats in both groups were under hypothermia treatment for five days. Four and eight days later （ three days from rewarming）, rat brain tissues were obtained to detect the expressions of proliferating cell nuclear antigen （PCNA）, nestin, neuron-specific enolase （NSE） and glial fibrillary acidic protein （GFAP） by immunohistochemical method and to detect the apoptosis by in situ hybridization. Finally, the nerve function scores were obtained for evaluation of the nerve function. Results The ELISA showed that the high level of BDNF expression was at 48 to 60 hours after gene transfection. PCNA and nestin were highly expressed, while NES and GFAP showed nil or low level of expression in both groups at the fourth day after hypothermia, with little apoptotic cells especially in the Group B （P 〈0.05）. The expressions of PCNA and nestin were decreased, but the expressions of NSE and GFAP were increased at the third day after rewarming. The positive rate of NSE expression in the Group B was much higher and the apoptotic cells were much less compared with the Group A （ P 〈 0. 05 ）. A better nerve score was obtained in the Group B. Conclusion BDNF can enhance the survival rate of the transplanted stem cells and induce their differentiation into neurons under hypothermia. Key words: Craniocerebral trauma; Stem cells; Brain-derived neurotrophic factor; Hypothermia

Antidepressant Effects of a Plant-Derived Flavonoid Baicalein Involving Extracellular Signal-Regulated Kinases Cascade

Depression and related mood disorders are among the world's greatest public health problems. Previous studies have demonstrated that baicalein (Bai), one plant-derived active flavonoid, exhibits neuroprotection against ischemic brain injury and stimulates the levels of phosphorylation of extracellular signal-regulated kinase (pERK) and brain-derived neurotrophic factor (BDNF) expression in vivo. In this study, the antidepressant-like effects of baicalein was investigated using acute and chronic animal models of depression. The results showed that acute application of Bai at doses of 1, 2 and 4 mg/kg by intraperitoneal injection (i.p.) significantly reduced the immobility time in the forced swimming test (FST) and tail suspending test (TST) of mice. In addition, the chronic application of Bai by i.p. for 21 d also reduced the immobility time and improved locomotor activity in chronic unpredictable mild stress (CMS) model rats. Furthermore, it was shown that Bai reversed the reduction of extracellular ERKs phosphorylation and the level of BDNF expression in the hippocampus of CMS model rats. These results suggest that Bai produce an antidepressant-like effect and this effect is at least partly mediated by hippocampal ERK-mediated neurotrophic action.

Proliferative Retinopathy Is Associated with Impaired Increase in BDNF and RANTES Expression Levels after Preterm Birth

Background: Extremely preterm delivery is, amongst other complications, associated with retinopathy of prematurity (ROP). Untreated, ROP can progress to visual impairment and blindness due to an overgrowth of new vessels in the retina and vitreous cavity. Objective: The aim of this study was to identify cytokine markers within the first weeks of life that could be used to predict the risk for development of ROP later in life. Methods: Serum levels of 27 different cytokines in infants born at gestational weeks 23–30 were analyzed using a multiplex immunoassay method and compared between infants who did not develop ROP and infants who later developed proliferative ROP. In addition, mRNA levels of brain-derived neurotrophic factor (BDNF) in retinas from mice exposed to hyperoxia were analyzed using quantitative real-time PCR. Results: At birth, serum levels of IL-5 were higher in infants with no ROP compared to infants with proliferative ROP. 10–14 days after birth, serum levels of BDNF and RANTES were lower in infants who later developed proliferative ROP compared to infants who did not develop ROP. Furthermore, mRNA expression levels of BDNF in retinas from mice exposed to hyperoxia were significantly lower at postnatal day 15 compared to retinas from mice in room air. Conclusions: These results indicate that BDNF and RANTES may be important factors in the selective vulnerability of ROP development in preterm infants.

Chronic antidepressant administration alleviates frontal and hippocampal BDNF deficits in CUMS rat

Stress activates the hypothalamo–pituitary–adrenal (HPA) axis, regulates the expression of brain-derived neurotrophic factor (BDNF) in the brain, and mediates mood. Antidepressants alleviate stress and up-regulate BDNF gene expression. In this study, we investigated the effect of chronic unpredictable mild stress (CUMS) and the different kinds of antidepressant treatments on the HPA axis and the BDNF expression in the rat brain. Adult Wistar male rats were exposed to a six-week CUMS procedure and received different antidepressant treatments including venlafaxine, mirtazapine, and fluoxetine. Immunohistochemistry and real-time PCR were used to measure BDNF expression levels in the rat brain, and ELISAs were used to investigate the plasma corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels. CUMS significantly decreased the BDNF protein level in the DG, CA1, and CA3 of the hippocampus and increased plasma CORT level. Chronic antidepressant treatments all significantly increased BDNF protein levels in the hippocampus and the pre-frontal cortex. In addition, venlafaxine and mirtazapine inhibited the increase of plasma CORT level. These results suggested that an increase in the BDNF level in the brain could be a pivotal mechanism of various antidepressants to exert their therapeutic effects.

Expression of brain-derived neurotrophic factor in mature spermatozoa from fertile and infertile men

Background Neurotrophins, a family of growth factor, are not only required for the survival and differentiation of the nervous system but also important for the development of reproductive tissues. We identified the expression of brain-derived neurotrophic factor (BDNF) transcript and protein in human spermatozoa. Methods The presence of BDNF in human spermatozoa was investigated using RT-PCR, immunofluorescence and Western blotting. Real-time PCR and ELISA were employed to determine expression levels of BDNF. Results BDNF mRNA and protein were detected in human spermatozoa. Immunofluorescence staining showed that BDNF protein was localized in the head, neck, and tail of human spermatozoa. The amount of BDNF mRNA expressed in spermatozoa of oligoasthenozoospermic group was lower than that of fertile group ( P < 0.05). The concentration of BDNF in seminal plasma from oligoasthenozoospermic group (2.8 ± 0.7 ng/ml) was both lower than that from fertile group (3.6 ± 0.4 ng/ml) and asthenozoospermic group (3.4 ± 0.5 ng/ml) ( P < 0.05). Conclusions The data showed that the decrease in BDNF transcript and protein in oligoasthenozoospermic group may be associated with pathogenesis in some types of male infertility.

Differential expression of brain derived neurotrophic factor (BDNF) and its receptor TrkB in luteinized human mural and cumulus granulosa cells

OBJECTIVE: Characterization of human luteinized mural and cumulus granulosa cell expression of neurotrophins nerve growth factor (NGF) and (BDNF) and their receptors TrkA, TrkB and p75NTR. DESIGN: Prospective clinical and laboratory study. MATERIALS AND METHODS: Mural and cumulus granulosa cells were collected from 23 women (age range: 26-46) undergoing controlled ovarian hyperstimulation (COH) in preparation for ART. Fifteen women with male or tubal factor infertility and 8 women with diminished ovarian reserve (DOR, diagnosed by day 3 FSH>10IU/L) were included. Mural and cumulus cell mRNA was isolated and gene expression of NGF, BDNF, TrkA, TrkB and p75NTR was quantified and normalized to GAPDH by qRT-PCR. Data were analyzed using correlation analysis as appropriate, Student t–test and expressed as Mean ± SEM. RESULTS: BDNF mRNA expression was almost 2-fold higher in cumulus than in mural cells (6.4 ± 0.9 vs 3.5 ± 0.5, p=0.004). Similarly, expression of the BDNF receptor TrkB was almost 3–fold higher in cumulus than in mural cells (71.6 ± 8.9 vs 25.4 ± 4.5, p<0.0001). Conversely, expression of NGF, its receptor TrkA, and the common low affinity receptor p75NTR was not different in mural and cumulus granulosa cells. BDNF and TrkB expression levels were not associated with the maximum historical FSH, AMH or number of oocytes retrieved during COH-ART cycles. CONCLUSION: We demonstrate for the first time that expression of BDNF and its receptor TrkB is significantly increased in cumulus vs mural granulosa cells. We also demonstrate a lack of association between BDNF/TrkB mRNA levels and clinical indicators of DOR. Further experiments are needed to determine whether BDNF and TrkB are important in cumulus granulosa cell differentiation.

Mismatch between changes in baicalein-induced memory-related biochemical parameters and behavioral consequences in mouse

Baicalein is one of the major flavonoids originally isolated from the roots of Scutellaria baicalensis Georgi (Labiatae). Reports on baicalein-induced changes in memory-related biochemical parameters including extracellular signal-regulated kinases (ERK), Akt, cAMP response element-binding protein (CREB), and brain-derived neurotrophic factor (BDNF) have been scarce, and the action of baicalein is controversial. Baicalein promotes phosphorylation of ERK under normal conditions; on the other hand, it inhibits phosphorylation of ERK extracellularly under oxidative conditions. In the present study, we observed that baicalein (20 mg/kg, p.o.) as compared to vehicle significantly increased the expression of phosphorylated ERK (pERK), phosphorylated CREB (pCREB), and BDNF but did not increase phosphorylated Akt expression in the hippocampus of naive mice. Baicalein also significantly increased the expression of pERK and BDNF in the cortex of naive mice. However, baicalein had no effect on memory acquisition in the step-through passive avoidance task. On the contrary, baicalein (20 mg/kg, p.o.) co-injected with flumazenil (10 mg/kg, i.p.) significantly increased the retention latency in the passive avoidance task in comparison to the flumazenil-treated group, baicalein-treated group, and vehicle-treated control group. In addition, the number of platform crossings in the Morris water maze test during the probe trial session was significantly increased by co-administration of baicalein with flumazenil. Furthermore, the expressions level of BDNF was significantly increased in the baicalein with flumazenil-treated group compared to the baicalein- or flumazenil-treated groups in the hippocampus after an acquisition trial. These results suggest that the reasons why baicalein does not exert cognitive enhancement although it enhances the expression levels of pERK, pCREB, and BDNF are, in part, derived from its GABA A receptor agonistic property which is antagonized by flumazenil.

Antidepressant-like activity of the aqueous extract of Allium macrostemon in mice

Aim of the study The aim of this study was to identify the effects of water extracts of Allium macrostemon Bunge (AM-W), a traditional herb, in mice. Materials and methods The antidepressant-like activities of AM-W were evaluated through behavioral despair in forced swimming test and tail suspension test. To elucidate the mode of action of the antidepressant-like effects of AM-W, new born cells in the subgranular zone and the granule cell layer were analyzed by immunostaining for incorporation of 5-bromo-2-deoxyuridine (BrdU). In addition, the effects of AM-W on the expression levels of brain-derived neurotrophic factor (BDNF) were investigated by western blotting and immunohistochemistry. Results The administration of AM-W reduced the immobility duration in the forced swimming test and tail suspension test (100 or 200 mg/kg, P < 0.05). Sub-chronic administration of AM-W (100 or 200 mg/kg, p.o., for 14 days) increased the number of BrdU-incorporating cells. The percentage of BrdU-incorporating cells co-localized with NeuN was significantly increased after AM-W administration (100 or 200 mg/kg, P < 0.05). Moreover, the expression levels of BDNF which is reported to be associated with neurogenesis were significantly increased in the hippocampus after administration of AM-W. Conclusions These results suggest that AM-W may be a good antidepressant, and that its mechanism of action may be related to its positive effects on neurogenesis and BDNF release.

Anxiolytic effect of music exposure on BDNF Met/Met transgenic mice

Brain-derived neurotrophic factor (BDNF) has been reported to play important roles in the modulation of anxiety, mood stabilizers, and pathophysiology of affective disorders. Recently, a single nucleotide polymorphism (SNP) in the BDNF gene (Val66Met) has been found to be associated with depression and anxiety disorders. The humanized BDNF Met/Met knock-in transgenic mice exhibited increased anxiety-related behaviors that were unresponsive to serotonin reuptake inhibitors, fluoxetine. Music is known to be able to elicit emotional changes, including anxiolytic effects. In this study, we found that music treatment could significantly decrease anxiety state in BDNF Met/Met mice, but not in BDNF +/ −, mice compared with white noise exposure in open field and elevated plus maze test. Moreover, in contrast to white noise exposure, BDNF expression levels in the prefrontal cortex (PFC), amygdala and hippocampus were significantly increased in music-exposed adult BDNF Met/Met mice. However, music treatment could not upregulate BDNF levels in the PFC, amygdala, and hippocampus in BDNF +/ − mice, which suggests the essential role of BDNF in the anxiolytic effect of music. Together, our results imply that music may provide an effective therapeutic intervention for anxiety disorders in humans with this genetic BDNF Met variant.

Chronic Administration of Cyclosporine A Changes Expression of BDNF and TrkB in Rat Hippocampus and Midbrain

Neurotrophins, including the brain-derived neurotrophic factor (BDNF), are essential for regulating neuronal differentiation in developing brains. BDNF and its receptor tyrosine kinase receptor B (TrkB) are involved in neuronal signaling, survival and plasticity. Cyclosporine A (CsA) is a potent immunosuppressive agent which prevents allograft rejection in organ transplantation and various immunological diseases. We investigated whether chronic administration of CsA decreases BDNF gene expression in rats, and the influence of CsA on mRNA levels of TrkB receptors was also examined. For 30 days of CsA (10 mg/kg/day) administration, the expression of BDNF and TrkB mRNA was significantly decreased in the hippocampus and midbrain, but there was no significant difference in the cortex. CsA (0, 1, 5 10, 15 ug/ml) down-regulated BDNF and TrkB gene expression through cultured SH-SY5Y cells, as did all-trans retinoic acid (ATRA), and there was no effect on cell viability. These experimental results indicate that suppression of the BDNF and TrkB mRNA, protein level of BDNF expression in the hippocampus and midbrain may be related to altered behavior observed following chronic administration of CsA. A common mechanism of adverse effects of CsA induced depressive symptoms may involve neurotoxicity mediated by down-regulation of brain BDNF and TrkB.

Spatial Learning and Expression Patterns of PP1 mRNA in Mouse Hippocampus

Background: Synaptic plasticity is believed to be the major cellular basis for learning and memory. Protein phosphorylation is a key process involved in changes in the efficacy of neurotransmission. In long-term changes synaptic plasticity is followed by structural plasticity and protein de novo synthesis. Such mechanisms are believed to build the basis of hippocampal learning and memory investigated in the Morris water maze (MWM) task. To examine the role of dephosphorylation during that model for spatial learning, we analyzed protein phosphatase 1 (PP1) expression in the hippocampus of mice at various stages of the task and in two groups with different learning abilities. Methods: Mice were trained for 4 days with four trials each day in the MWM. For gene expression hippocampi were prepared 1, 6 and 24 h after the last trial of each day. PP1 and brain-derived neurotrophic factor (BDNF) mRNA levels were determined by quantitative real-time PCR. Results: The task requirements themselves affected expression levels of both PP1 and BDNF. In contrast to BDNF, PP1 was differentially expressed during learning. Poorly and well performing mice differed significantly. When performance was poor the expression level of PP1 was higher. Conclusion: Present results add further in vivo evidence that not only phosphorylation but also dephosphorylation is a major mechanism involved in learning and memory. Therefore, inhibition of hippocampal phosphatase activity might improve learning and memory.

Effects of Yiqi Huayu Decoction on brain-derived neurotrophic factor expression in rats with lumbar nerve root injury

To observe the effects of Yiqi Huayu Decoction, a compound traditional Chinese herbal medicine, on brain-derived neurotrophic factor (BDNF) expression in lumbar nerve root and soleus of rats after lumbar nerve root compression injury. A total of 120 male SD rats were randomly allocated into sham-operated group, untreated group, methycobal injection group and Yiqi Huayu Decoction group. Surgery were performed on rats of untreated group, methycobal injection group and Yiqi Huayu Decoction group by placing a micro-silica gel on right L(4) dorsal root ganglia, while rats in sham-operated group received skin and paravertebral muscle incision only. Rats in the methycobal injection group and the Yiqi Huayu Decoction group were given intramuscular injection of methycobal and intragastric administration of Yiqi Huayu Decoction respectively. Rats in the sham-operated group and the untreated group received intragastric administration of normal saline of equal volume as Yiqi Huayu Decoction. The compressed nerve roots and right soleus were harvested after 10-, 30- and 60-day treatment. Microstructure of the compressed nerve roots were revealed under a transmission electron microscope. BDNF protein expression in the compressed nerve roots and mRNA expression in right solues were detected with enzyme-linked immunosorbent assay (ELISA) and real-time quantitative reverse transcription-polymerase chain reaction respectively. The protein expression level of BDNF in compressed nerve root in the untreated group was slightly changed with no significance as compared with sham-operated group. BDNF protein expression in the Yiqi Huayu Decoction group was gradually increased and reached the peak level after 60-day treatment with significant difference as compared with the untreated group (P<.01). The expression of BDNF mRNA in soleus was significantly up-regulated 10 days after nerve root injury (P<0.01), and was slowly decreased to the normal level at day 60 (P>0.05). Compared with the untreated group, BDNF mRNA expression in soleus muscle in the Yiqi Huayu Decoction group was significantly down-regulated after 10-day treatment (P<0.01), while was increased after 60-day treatment (P<0.01). Yiqi Huayu Decoction can inhibit the increase of BDNF expression at the early phase after nerve injury, which may have something to do with alleviation of neuropathic pain, and increase BDNF expression at the late phase to promote nerve regeneration.

Synergistic Increase of BDNF Release from Rat Primary Cortical Neuron by Combination of Several Medicinal Plant-Derived Compounds

Abstract － Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor involved in neuronal differentiation, plasticity, survival and regeneration. BDNF draws massive attention mainly due to the potential as a therapeutic target in neurological diseases such as depression and Alzheimer’s disease. In a primary screening for the natural compounds enhancing BDNF release from cultured rat primary cortical neuron, we found that compounds such as baicalein, tanshinone IIa, cinnamic acid, epiberberine, genistein and wogonin among many others increased BDNF release. All the compounds at 0.1 μM of concentration barely showed stimulatory effect on BDNF induction, however, their combination (mixture 1; baicalein, tanshinone IIa and cinnamic acid, mixture 2; epiberberine, genistein and wogonin) showed synergistic increase in BDNF release as well as mRNA and protein expression. The level of BDNF expression was comparable to the maximum BDNF stimulation attainable by a positive control oroxylin A (20 μM) without cell toxicity as determined by MTT analysis. Both mixtures synergistically increased the phosphorylation of extracellular signal-regulated kinase (ERK) as well as cAMP response element binding protein (CREB), an immediate and essential regulator of BDNF expression. Similar to these results, mixture of these compounds synergistically inhibited the up-regulation of inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide treatments in rat primary astrocytes. These results suggest that the combinatorial treatment of natural compounds in lower concentration might be a useful strategy to obtain sufficient BDNF stimulation in neurological disease condition such as depression, while minimizing potential side effects and toxicity of higher concentration of a single compound.Keywords: BDNF, Cortical neuron, CREB, ERK, Synergism

Neonatal caffeine treatment does not induce long-term consequences on TrkB receptors or BDNF expression in chemosensory organs of adult rats

Chronic treatment with caffeine during the neonatal period (neonatal caffeine treatment, NCT, 15 mg/kg/day from P3 to P12, oral gavage) has long-lasting consequences on respiratory control development. In adult male (but not female) rats, prior exposure to NCT results in a greater respiratory frequency response to hypoxia. This sex-specific effect of NCT was accompanied by an augmented expression of adenosine A 2A receptors (A 2AR) in the carotid body (CB) but not in the nucleus tractus solitarius (NTS). Since activation of adenosine A 2AR can directly stimulate synthesis of tyrosine kinase B receptor (TrkBR) and brain-derived neurotrophic factor (BDNF), we determined whether NCT increases TrkBR and BDNF expression levels in the CB and NTS using both RT-PCR and western blot analyses. CB, NTS, and superior cervical ganglion were collected from adult male and female rats (10–12 weeks old) previously subjected to NCT or to control (neonatal water treatment, NWT). In male rats, when NCT tended to decrease TrkBR mRNA transcript levels by about 32% in the CB and to reduce BDNF transcripts in the NTS by 22%, western blot analyses showed no parallel changes in final protein expression. NCT had no effects on TrkBR or BDNF mRNA and protein levels in the CB and NTS of female rats. Neither gene was altered by NCT in the superior cervical ganglion of male and female rats. These data suggest that NCT has no long-term effects on trophic factor BDNF and TrkBR expression at peripheral and central level of chemosensory organs involved in respiratory control.

Brain-derived Neurotrophic Factor Enhances the Basal Rate of Protein Synthesis by Increasing Active Eukaryotic Elongation Factor 2 Levels and Promoting Translation Elongation in Cortical Neurons

The constitutive and activity-dependent components of protein synthesis are both critical for neural function. Although the mechanisms controlling extracellularly induced protein synthesis are becoming clear, less is understood about the molecular networks that regulate the basal translation rate. Here we describe the effects of chronic treatment with various neurotrophic factors and cytokines on the basal rate of protein synthesis in primary cortical neurons. Among the examined factors, brain-derived neurotrophic factor (BDNF) showed the strongest effect. The rate of protein synthesis increased in the cortical tissues of BDNF transgenic mice, whereas it decreased in BDNF knock-out mice. BDNF specifically increased the level of the active, unphosphorylated form of eukaryotic elongation factor 2 (eEF2). The levels of active eEF2 increased and decreased in BDNF transgenic and BDNF knock-out mice, respectively. BDNF decreased kinase activity and increased phosphatase activity against eEF2 in vitro. Additionally, BDNF shortened the ribosomal transit time, an index of translation elongation. In agreement with these results, overexpression of eEF2 enhanced protein synthesis. Taken together, our results demonstrate that the increased level of active eEF2 induced by chronic BDNF stimulation enhances translational elongation processes and increases the total rate of protein synthesis in neurons.

Comparison of the Temporary Dynamics of NGF and BDNF Gene Expression in Rat Hippocampus, Frontal Cortex, and Retina Under Semax Action

Neurotrophins are a family of structurally related proteins that regulate the survival, differentiation, and maintenance of function of different neuron populations. Some peptides are able to affect the production and activity of neurotrophins. One of these synthetic peptides is heptapeptide Semax, an analog of the N-terminal adrenocorticotropic hormone fragment 4-10. It is known that Semax has effects on learning and memory formation and exerts some neuroprotective effects in rodents and humans. Male Wistar rats were treated for 20 min, 40 min, 90 min, 3 h, 8 h, and 24 h with Semax. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) gene expression in rat brain and retina was analyzed by real-time polymerase chain reaction. It was revealed that after Semax administration the multidirectional activation of the expression of the genes under investigation in the hippocampus, frontal cortex, and retina was observed. The expression of both neurotrophin genes was decreased in rat hippocampus and retina 20 min after Semax administration and was increased in the frontal cortex. The expression levels of NGF remained practically constant in the retina at the initial stage, whereas the expression levels of BDNF were significantly increased 90 min after Semax administration.

Cumulus gene expression as a predictor of human oocyte fertilisation, embryo development and competence to establish a pregnancy

The close relationship between cumulus cell function and oocyte developmental competence indicates that analysis of cumulus gene expression is a potential non-invasive method to aid embryo selection and IVF outcome. Cumulus was isolated from 674 oocytes from 75 women undergoing ICSI and gene expression analysed by quantitative RT-PCR. Cumulus expression of cyclooxygenase 2 (PTGS2) was higher with mature oocytes, whereas brain-derived neurotrophic factor (BDNF) was lower when fertilisation was normal. Expression levels of gremlin (GREM1) and BDNF were weak positive and negative predictors of embryo quality respectively. Ranking of GREM1 expression within cohorts of oocytes showed that oocytes associated with the highest GREM1 expression were more likely to be transferred or cryopreserved than discarded (49 vs 33%, P<0.02), although the clinical pregnancy rate was not significantly different. This study demonstrates both the feasibility and difficulties of this method of analysis in the largest such group studied thus far. Novel relationships between BDNF expression and fertilisation were identified, and the potential value of GREM1 expression as a marker of embryo quality supports the further assessment of GREM1 analysis in the context of embryo selection.

BDNF is not associated with schizophrenia: Data from a Japanese population study and meta-analysis

A variety of evidence suggests brain-derived neurotrophic factor ( BDNF) as a candidate gene for schizophrenia, and several genetic studies have shown a significant association between the disease and certain SNPs within BDNF (specifically, Val66Met and C270T). According to a recent study, the functional microsatellite marker BDNF-LCPR ( BDNF-linked complex polymorphic region), which affects the expression level of BDNF, is associated with bipolar disorder. The goals of our current study were to 1) evaluate the quality of HapMap-based linkage disequilibrium (LD) tagging of BDNF-LCPR, 2) examine whether these tagging SNPs are associated with schizophrenia in a Japanese population, and 3) conduct a meta-analysis of the two most extensively studied polymorphisms: Val66Met and C270T. We genotyped eight tagging SNPs, including Val66Met and C270T. Our LD evaluation showed that BDNF-LCPR could be represented by these tagging SNPs in controls (with 73.5% allelic coverage). However, the functional A1 allele was not captured due to its low minor allele frequency (2.2%). In a case-control study (1117 schizophrenics and 1102 controls), no association was found in single-marker or multimarker analysis. Moreover, in a meta-analysis, the Val66Met polymorphism was not associated with schizophrenia, whereas C270T showed a trend for association in a fixed model ( p = 0.036), but not in a random model ( p = 0.053). From these findings, we conclude that if BDNF is indeed associated with schizophrenia, the A1 allele in BDNF-LCPR would be the most promising candidate. Further LD evaluation, as well as an association study in which BDNF-LCPR is genotyped directly, would be required for a more conclusive result.