Higher Brain-derived Neurotrophic Factor Levels Research Articles

Additive clinical value of serum brain-derived neurotrophic factor for prediction of chronic heart failure outcome.

The importance of the central nervous system in cardiovascular events has been recognized. Recently, brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, is involved in depression mechanisms and also in stress and anxiety. Because BDNF is reported about cardioprotective role, we elucidated whether BDNF is associated with cardiovascular events in patients with chronic heart failure (CHF). We examined serum BDNF levels in 134 patients with CHF and 23 control subjects. The patients were followed to register cardiac events for a median of 426 days. BDNF was significantly lower in CHF patients than in control subjects (25.8 ± 8.4 vs 14.7 ± 8.4, P < 0.0001). Serum BDNF was also lower in patients with cardiac events than in event-free patients (16.1 ± 8.0 vs 12.5 ± 8.5, P < 0.0001). The cutoff value of BDNF was determined by performing receiver operating characteristic curve analysis. Kaplan-Meier analysis demonstrated that patients with low levels of BDNF experienced higher rates of cardiac events than those with high levels of BDNF. Multivariate Cox hazard analysis demonstrated that low BDNF levels (≤12.4 ng/mL) were an independent prognostic factor for cardiac events (hazard ratio 2.932, 95 % confidence interval 1.622-5.301; P = 0.0004). Adding levels of BDNF to the model with BNP levels, age, and eGFR for the prediction of cardiac events yielded significant net reclassification improvement of 0.429 (P < 0.001) and an integrated discrimination improvement of 0.101 (P < 0.001). Low serum BDNF levels were found in patients with CHF, and these levels were found to be independently associated with an increased risk of cardiac events.

Serum BDNF: A Potential Biomarker for Major Depressive Disorder and Antidepressant Response Prediction

Background: The neurotrophin hypothesis of depression emphasizes the role of down-regulation of Brainderived Neurotrophic Factor (BDNF) in the pathophysiology of Major Depressive Disorder (MDD). Patients with MDD may have reduced serum BDNF levels and treatment with antidepressants may stimulate the expression of BDNF resulting in normalization of BDNF after successful treatment. Objective: To determine whether serum BDNF in MDD patients is lower than in healthy control (HC) subjects, whether all MDD patients show lower than normal levels and whether MDD patients with comparatively higher BDNF levels will respond better to antidepressant therapy. Method: Ninety medically healthy outpatients diagnosed with MDD were enrolled in one of two studies. In Study-1 patients were treated with escitalopram and in Study-2 with quetiapine. The main outcome measure was the 17-item Hamilton Depression Scale (HAM-D) scores. Of the 90 enrolled patients 54 had baseline BDNF values. Thirteen HC subjects for whom serum BDNF values were available were included for comparison. Results: Mean baseline serum BDNF did not differ between MDD and HC subjects. When the median BDNF value was used as a “cut score” to subdivide the MDD group into an above median (high) and a below median (low) subgroup, significant differences emerged. Both subgroups differed significantly from the HC mean and from each other. Depressive episodes of greater than 6 months’ duration correlated significantly with higher BDNF levels (p=0.03). Higher BDNF levels predicted a high probability of a positive treatment response (p=0.02) to either of the two pharmacologic agents used. Conclusions: Serum BDNF levels can be higher or lower in MDD subjects when compared to healthy controls. A high baseline BDNF level may predict a positive treatment response to antidepressant drug therapy, suggesting a possible future role of serum BDNF level as a useful biomarker for subtyping MDD and predicting antidepressant treatment response.

Protective Effects of BDNF against C-Reactive Protein-Induced Inflammation in Women.

Background. Since high sensitivity C-reactive protein (hsCRP) is predictive of cardiovascular events, it is important to examine the relationship between hsCRP and other inflammatory and oxidative stress markers linked to cardiovascular disease (CVD) etiology. Previously, we reported that hsCRP induces the oxidative stress adduct 8-oxo-7,8-dihydro-2′deoxyguanosine (8-oxodG) and that these markers are significantly associated in women. Recent data indicates that brain-derived neurotrophic factor (BDNF) may have a role in CVD. Methods and Results. We examined BDNF levels in 3 groups of women that were age- and race-matched with low (<3 mg/L), mid (>3–20 mg/L), and high (>20 mg/L) hsCRP (n = 39 per group) and found a significant association between hsCRP, BDNF, and 8-oxodG. In African American females with high hsCRP, increases in BDNF were associated with decreased serum 8-oxodG. This was not the case in white women where high hsCRP was associated with high levels of BDNF and high levels of 8-oxodG. BDNF treatment of cells reduced CRP levels and inhibited CRP-induced DNA damage. Conclusion. We discovered an important relationship between hsCRP, 8-oxodG, and BDNF in women at hsCRP levels >3 mg/L. These data suggest that BDNF may have a protective role in counteracting the inflammatory effects of hsCRP.

Differences in BDNF Serum Levels in Patients with AlzheimerÂ’s Disease and Mild Cognitive Impairment

Objectives: A great deal of research has been conducted into the possible involvement of neurotrophins such as brain-derived neurotrophic factor (BDNF) in the pathogenesis of Alzheimer’s disease (AD). We hypothesized that lower BDNF serum levels may be associated with cognitive decline. To test this hypothesis, we examined the differences in the serum BDNF levels in patients with AD and mild cognitive impairment (MCI) and normal controls. Method: We enrolled 56 subjects with AD, 29 subjects with MCI, and 24 healthy control subjects in the study. A total of 109 subjects agreed to blood sampling to evaluate serum BDNF levels. Serum levels of BDNF were measured using an enzyme-linked immunosorbent assay (ELISA) method. Results: The MCI group had higher BDNF levels as compared to the AD group (p=0.027). However, there were no significant differences between either the AD group or the MCI group and the control group. A significant correlation was observed between MMSE-K score and serum BDNF level. However, BDNF serum concentrations did not significantly correlate with age or level of education in the AD, MCI, and control groups. Conclusion: Our data suggest that BDNF serum levels are increased in subjects with MCI, supporting the hypothesis of an upregulation of BDNF in preclinical stages. BDNF levels might be involved in the pathophysiology of cognitive decline in elderly people.

Effect of spontaneous seizures on GABAA receptor α4 subunit expression in an animal model of temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is frequently medically intractable and often progressive. Compromised inhibitory neurotransmission due to altered γ-aminobutyric acid (GABA)A receptor α4 subunit (GABAA Rα4) expression has been emphasized as a potential contributor to the initial development of epilepsy following a brain insult (primary epileptogenesis), but the regulation of GABAA Rα4 during chronic epilepsy, specifically, how expression is altered following spontaneous seizures, is less well understood. Continuous video-electroencephalography (EEG) recordings from rats with pilocarpine-induced TLE were used to capture epileptic animals within 3h of a spontaneous seizure (SS), or >24h after the last SS, to determine whether recent occurrence of a seizure was associated with altered levels of GABAA Rα4 expression. We further evaluated whether this GABAA Rα4 plasticity is regulated by signaling mechanisms active in primary epileptogenesis, specifically, increases in brain-derived neurotrophic factor (BDNF) and early growth response factor 3 (Egr3). Elevated levels of GABAA Rα4 messenger RNA (mRNA) and protein were observed following spontaneous seizures, and were associated with higher levels of BDNF and Egr3 mRNA. These data suggest that spontaneous, recurrent seizures that define chronic epilepsy may influence changes in GABAA Rα4 expression, and that signaling pathways known to regulate GABAA Rα4 expression after status epilepticus may also be activated after spontaneous seizures in chronically epileptic animals.

Serum brain-derived neurotrophic factor and cognitive functioning in underweight, weight-recovered and partially weight-recovered females with anorexia nervosa.

Several studies support the assumption that the brain-derived neurotrophic factor (BDNF) plays an important role in the pathophysiology of eating disorders. In the present cross-sectional and longitudinal study, we investigated BDNF levels in patients with anorexia nervosa (AN) at different stages of their illness and the association with cognitive functioning. We measured serum BDNF in 72 acutely underweight female AN patients (acAN), 23 female AN patients who successfully recovered from their illness (recAN), and 52 healthy control women (HCW). Longitudinally, 30 acAN patients were reassessed after short-term weight gain. The association between BDNF levels and psychomotor speed was investigated using the Trail Making Test. BDNF serum concentrations were significantly higher in recAN participants if compared to acAN patients and increased with short-term weight gain. In acAN patients, but not HCW, BDNF levels were inversely associated with psychomotor speed. AcAN patients with higher BDNF levels also had lower life time body mass indexes. Taken together, our results indicate that serum BDNF levels in patients with AN vary with the stage of illness. Based on the pleiotropic functions of BDNF, changing levels of this neurotrophin may have different context-dependent effects, one of which may be the modulation of cognitive functioning in acutely underweight patients.

Sign-tracking to an appetitive cue predicts incubation of conditioned fear in rats

Although post-traumatic stress disorder (PTSD) and addiction are very different disorders, both are characterized by hyperreactivity to trauma- or drug-related cues, respectively. We investigated whether an appetitive conditioning task, Pavlovian conditioned approach, which predicts vulnerability to reinstatement of cocaine-seeking, also predicts fear incubation, which may be a marker for vulnerability to PTSD. We classified rats based on whether they learned to approach and interact with a food predictive cue (sign-trackers), or, whether upon cue presentation they went to the location of impending food delivery (goal-trackers). Rats were then exposed to extensive Pavlovian tone-shock pairings, which causes the fear response to increase or “incubate” over time. We found that the fear incubation effect was only present in sign-trackers. The behavior of goal-trackers was more consistent with a normal fear response–it was most robust immediately after training and decayed slowly over time. Sign-trackers also had lower levels of brain-derived neurotrophic factor (BDNF) protein in the prefrontal cortex than goal-trackers. These results indicate that, while many factors likely contribute to the disproportionate co-occurrence of PTSD and substance abuse, one such factor may be a core psychological trait that biases some individuals to attribute excessive motivational significance to predictive cues, regardless of the emotional valence of those cues. High levels of BDNF in the prefrontal cortex may be protective against developing excessive emotional and motivational responses to salient cues.

Increased levels of neurotrophins in the cerebrospinal fluid of children with Epstein–Barr virus meningoencephalitis

The aim of this study was to evaluate the expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in the cerebrospinal fluid (CSF) of children with Epstein-Barr virus (EBV)-induced meningoencephalitis (ME) in order to establish a possible correlation with laboratory findings and neurological manifestations. A prospective observational clinical study was performed on 10 children with viral ME, five of them with EBV-induced ME. As controls, we used CSF samples collected from children admitted with febrile seizures. Neurotrophin levels were measured using an enzyme immunoassay. Significantly higher levels of BDNF and NGF were detected in all patients with viral ME compared to controls. Moreover, in patients with EBV-induced ME, the neurotrophin levels were higher than in those with other viral ME. Of note, in children with EBV-induced ME, we found a significant correlation between neurotrophic factor levels and the number of lymphocytes in the CSF (p<0.001). In these patients we also found a significant correlation between BDNF expression and the blood platelet count (p<0.001). Interestingly, two patients with EBV-induced ME showed a correlation between neurotrophin increase and persistent brain abnormalities, such as prolonged alteration of mental status, psychomotor agitation, and athetosis. Viral ME induces an early and strong increased biosynthesis of neurotrophic factors. This neurotrophin over-expression is likely to play a key role in the mechanisms of neuronal inflammation and in the severity of brain damage, particularly in EBV-induced ME.

Brain-derived neurotrophic factor plasma levels in patients with Turner syndrome

Introduction: Brain-derived neurotrophic factor (BDNF) plays a key role in neural development and synaptic plasticity. BDNF is known to circulate in plasma and its levels are strictly linked to the sex hormones.Aim: The aim of this study was to assess the plasma BDNF concentration in patients with Turner syndrome (TS). This is a first of such study in TS women.Methods: 31 TS patients were enrolled to the study and compared with a control group (10 healthy, ovulatory women). We collected blood for measurement of BDNF plasma concentration, estradiol (E2) and gonadotrophins serum levels. The blood was taken after overnight fasting, in menstruating women in follicular phase.Results: We found that BDNF plasma concentration was significantly higher in the group of TS patients compared to the control group (mean 768.5 ± 194.9 pg/ml versus 407.2 ± 25.7 pg/ml; p < 0.0001). What is more, the BDNF levels in TS were not correlated to E2 levels, whereas in the control group, positive and strong correlation with E2 was found (r = 0.92; p < 0.0001). The testosterone concentration correlated strongly with BDNF levels in TS patients.Conclusions: In this study, we showed for the first time that TS patients has a higher BDNF levels than healthy ones and BDNF is not correlated with E2 concentration but tend to be related to testosterone. This study brings interesting insights to BDNF physiology.

High BDNF Levels May Offer Protection Against Alzheimer’s

Back to table of contents Next article Clinical & ResearchFull AccessHigh BDNF Levels May Offer Protection Against Alzheimer’sJoan Arehart-TreichelJoan Arehart-TreichelSearch for more papers by this authorPublished Online:7 Feb 2014https://doi.org/10.1176/appi.pn.2014.1a11AbstractIf BDNF is a factor that helps blocks development of Alzheimer’s and other dementias, then boosting BDNF levels might someday be a way to treat or prevent them.It appears that higher blood levels of brain-derived neurotrophic factor (BDNF) may be able to protect people against development of Alzheimer’s disease and other types of dementia, according to a study published online November 25 in JAMA Neurology.BDNF is widely expressed throughout the central nervous system, especially in the cerebral cortex and in the brain’s memory seat—the hippocampus. Moreover, researchers found a link between low blood levels of BDNF and a smaller hippocampus and poorer memory in older dementia-free adults. In light of these previous findings, Sudha Seshadri, M.D., a professor of neurology at Boston University, and colleagues conducted a study to see whether blood levels of BDNF might influence the risk for Alzheimer’s or other types of dementia.Their study included more than 2,000 individuals aged 60 or older (average age 72) in whom blood levels of BDNF were measured. Subjects were then followed for a decade to determine whether any of them developed Alzheimer’s disease or another type of dementia.A total of 117 subjects developed Alzheimer’s, while 23 developed another type of dementia. The researchers then assessed whether there were any correlations between subjects’ BDNF levels and their risk for Alzheimer’s or other types of dementia, while taking potential confounders—for example, age, gender, education, blood pressure, history of cardiovascular disease, diabetes, smoking status, and APOE-e4 status—into consideration.Such correlations did in fact appear. Each standard-deviation increment in BDNF was associated with a 33 percent lower risk for developing Alzheimer’s or another dementia. Compared with the bottom quintile, BDNF levels in the top quintile were associated with less than half the risk for Alzheimer’s or dementia. However, these links were restricted to men and women over age 80, women under age 80, and individuals with a college education or graduate degree.Thus, the researchers concluded, “Higher serum BDNF levels may protect against future occurrence of dementia and Alzheimer’s.”“This is a potentially important study from the perspective of reducing the risk of dementia,” Dilip Jeste, M.D., chair in aging at the University of California, San Diego, and immediate past APA president, told Psychiatric News. “BDNF has been previously shown to be related to lifestyle factors and interventions. One study even reported an increase in BDNF in individuals with schizophrenia who received cognitive enhancement therapy. Continued research on BDNF and related neurotrophic factors in people at risk of dementia is necessary to help develop interventions to treat and prevent cognitive deficits in older adults,” Jeste said.“This study highlights the beneficial neuroprotective effects of BDNF, especially for women, individuals with college degrees, or those who have lived past 80 years, and the possibility that serum BDNF could one day be a ‘blood test’ biomarker for the risk for developing dementia and Alzheimer’s disease,” geriatric psychiatrist Mohit Chopra, M.D., a lecturer in psychiatry at Harvard Medical School, said in an interview.This is indeed an eventuality, Seshadri agreed. Giving BDNF to older people might prevent or counter Alzheimer’s symptoms, she suggested. “We need to study the benefits and potential side effects of giving BDNF to people. Ways of doing this—such as using agonists that would cross the blood-brain barrier into the brain—are being studied. “Interestingly, lithium, long used in the treatment of bipolar disorder, has been found to increase BDNF levels in individuals with Huntington’s disease, Seshadri pointed out. So there is reason to believe that if lithium increases BDNF levels, then it might also possess some effectiveness against Alzheimer’s, she indicated. Preliminary evidence reported in the May 2012 Drugs and Aging bolsters this possibility.Finally, there is something that people can do on their own to increase their BDNF levels and possibly, as a result, lower their risk for Alzheimer’s, Seshadri and colleagues suggested in their study report. And that is to exercise, because “BDNF levels can be elevated through simple lifestyle measures such as increased physical activity.”She and her team will continue to conduct research in this domain, Seshadri said. “We plan to look at BDNF in younger individuals, average age 45, to see if it affects cognition at that age as well. And we will explore the mechanisms, genetic and otherwise, that may underlie BDNF’s impact on Alzheimer’s and dementia.”The study was funded by the National Institutes of Health. ■An abstract of “Serum Brain-Derived Neurotrophic Factor and the Risk for Dementia” is posted at http://archneur.jamanetwork.com/article.aspx?articleid=1779513. ISSUES NewArchived

A BDNF/TrKB autocrine loop stimulated by HBZ is involved in HTLV-1-infected cell-survival

Brain-Derived Neurotrophic Factor (BDNF) is a neurotrophin that generally promotes neuronal proliferation, survival and plasticity. These effects occur through cellular secretion and subsequent binding of BDNF to its cognate receptor, TrkB, which promotes paracrine and autocrine signaling cascades. A BDNF/TrkB autocrine loop has been implicated in the survival of cells representing several human cancers and is associated with poor prognosis. The HTLV-1 protein, HBZ, is localized to the nucleus where it is capable of deregulating gene expression. In this study, we found that HBZ increases expression of BDNF. There are a variety of transcriptional variants of BDNF, and HBZ increased expression of several of these. Furthermore, multiple transcriptional variants of BDNF were upregulated in HTLV-1-infected cells compared to normal CD4 cells. Expression of the TrkB receptor was also higher in HTLV-1-infected cells than in normal CD4 cells. This trend similarly occurred when comparing ATL patient and healthy donor specimens, with patient cells exhibiting higher levels of BDNF and TrkB expression. TrkB appeared to localize to the cytoplasmic membrane of HTLV-1-infected cells, suggesting a BDNF/TrkB loop contributes to the survival of these cells. This hypothesis was confirmed by chemically blocking the binding of BDNF to TrkB or by inhibiting TrkB signaling, as both treatments led to a significant increase in apoptosis. Together these results suggest that HBZ activates a BDNF/TrkB autocrine loop that enhances survival of HTLV-1-infected cells. This mechanism may ultimately facilitate the survival of ATL cells.

Physical training and hypertension have opposite effects on endothelial brain-derived neurotrophic factor expression

Changes in circulating brain-derived neurotrophic factor (BDNF) levels were reported in patients with or at risk for cardiovascular diseases associated with endothelial dysfunction, suggesting a link between BDNF and endothelial functionality. However, little is known on cardiovascular BDNF. Our aim was to investigate levels/localization, function, and relevance of cardiovascular BDNF. BDNF levels (western blotting) and localization (immunostaining) were assessed in the heart and aorta from rats with impaired (spontaneously hypertensive rats [SHR]), normal (Wistar Kyoto rats [WKY]), and improved (SHR and WKY subjected to physical training) endothelial function. BDNF levels were also measured in cultured endothelial cells (CECs) subjected to low and high shear stress. The cardiovascular effects of BDNF were investigated in isolated aortic rings and hearts. The results showed high BDNF levels in the heart and aorta, the expression being prominent in endothelial cells as compared with other cell types. Exogenous BDNF vasodilated aortic rings but changed neither coronary flow nor cardiac contractility. Hypertension was associated with decreased expression of BDNF in the endothelium, whereas physical training led to endothelial BDNF up-regulation not only in WKY but also in SHR. Exposure of CECs to high shear stress stimulated BDNF production and secretion. Cardiovascular BDNF is mainly localized within endothelial cells in which its expression is dependent on endothelial function. These results open new perspectives on the role of endothelial BDNF in cardiovascular health.

Serum Brain–Derived Neurotrophic Factor and Vascular Endothelial Growth Factor Levels Are Associated With Risk of Stroke and Vascular Brain Injury

Background and Purpose— Brain-derived neurotrophic factor (BDNF), a major neurotrophin and vascular endothelial growth factor (VEGF) have a documented role in neurogenesis, angiogenesis, and neuronal survival. In animal experiments, they impact infarct size and functional motor recovery after an ischemic brain lesion. We sought to examine the association of serum BDNF and VEGF with the risk of clinical stroke or subclinical vascular brain injury in a community-based sample. Methods— In 3440 Framingham Study participants (mean age, 65±11 years; 56% women) who were free of stroke/transient ischemic attack (TIA), we related baseline BDNF and logVEGF to risk of incident stroke/TIA. In a subsample with brain MRI and with neuropsychological tests available (n=1863 and 2104, respectively; mean age, 61±9 years, 55% women, in each), we related baseline BDNF and logVEGF to log-white matter hyperintensity volume on brain MRI, and to visuospatial memory and executive function tests. Results— During a median follow-up of 10 years, 193 participants experienced incident stroke/TIA. In multivariable analyses adjusted for age, sex, and traditional stroke risk factors, lower BDNF and higher logVEGF levels were associated with an increased risk of incident stroke/TIA (hazard ratio comparing BDNF Q1 versus Q2–Q4, 1.47; 95% confidence interval, 1.09–2.00; P =0.012 and hazard ratio/SD increase in logVEGF, 1.21; 95% confidence interval, 1.04–1.40; P =0.012). Persons with higher BDNF levels had less log-white matter hyperintensity volume (β±SE=−0.05±0.02; P =0.025), and better visual memory (β±SE=0.18±0.07; P =0.005). Conclusions— Lower serum BDNF and higher VEGF concentrations were associated with increased risk of incident stroke/TIA. Higher levels of BDNF were also associated with less white matter hyperintensity and better visual memory. Our findings suggest that circulating BDNF and VEGF levels modify risk of clinical and subclinical vascular brain injury.

Differential effects of exercise intensities in hippocampal BDNF, inflammatory cytokines and cell proliferation in rats during the postnatal brain development

It has been established that low intensities of exercise produce beneficial effects for the brain, while high intensities can cause some neuronal damage (e.g. exacerbated inflammatory response and cell death). Although these effects are documented in the mature brain, the influence of exercise intensities in the developing brain has been poorly explored. To investigate the impact of exercise intensity in developing rats, we evaluated the hippocampal level of brain derived neurotrophic factor (BDNF), inflammatory cytokines (TNFα, IL6 and IL10) and the occurrence of hippocampal cell degeneration and proliferation at different stages of postnatal brain development of rats submitted to two physical exercise intensities. To this point, male rats were divided into different age groups: P21, P31, P41 and P51. Each age group was submitted to two exercise intensities (low and high) on a treadmill over 10 consecutive days, except the control rats. We verified that the density of proliferating cells was significantly higher in the dentate gyrus of rats submitted to low-intensity exercise from P21 to P30 compared with high-intensity exercise and control rats. A significant increase of proliferative cell density was found in rats submitted to high-intensity exercise from P31 to P40 when compared to low-intensity exercise and control rats. Elevated hippocampal levels of IL6 were detected in rats submitted to high-intensity exercise from P21 to P30 compared to control rats. From P41 to P50 period, higher levels of BDNF, TNFα and IL10 were found in the hippocampal formation of rats submitted to high-intensity exercise in relation to their control rats. Our data show that exercise-induced neuroplastic effects on BDNF levels and cellular proliferation in the hippocampal region are dependent on exercise intensity and developmental period. Thus, exercise intensity is an inflammation-inducing factor and exercise-induced inflammatory response during the postnatal brain development is also related to developmental stage. Our findings indicate that neuroplastic changes induced by exercise in developing rats depend on both age and training intensity.

Progesterone, compared to medroxyprogesterone acetate, to C57BL/6, but not 5α-reductase mutant, mice enhances object recognition and placement memory and is associated with higher BDNF levels in the hippocampus and cortex

Progesterone (P4) may influence cognition in part through actions of its 5α-reduced metabolite, allopregnanolone. Ovariectomized mice that were C57BL/6 wildtype (WT), or deficient in the 5α-reductase Type 1 enzyme (5α-reductase knockout; 5αRKO), were administered vehicle, P4, allopregnanolone, or medroxyprogesterone acetate (MPA) after training in the object recognition or placement tasks. WT mice administered P4 or allopregnanolone performed significantly better in the object recognition and placement tasks than did WT mice administered vehicle or MPA. 5αRKO mice administered allopregnanolone, but not P4, MPA, or vehicle showed enhanced performance in the object recognition and placement tasks. Levels of brain-derived neurotrophic factor (BDNF) in the prefrontal cortex and hippocampus were lowest among mice administered MPA. Thus, some of P4s effects to enhance cognitive performance may be incumbent upon its 5α-reduction.

Transcription Factor SCIRR69 Involved in the Activation of Brain-Derived Neurotrophic Factor Gene Promoter II in Mechanically Injured Neurons

The spinal cord injury and regeneration-related gene #69 (SCIRR69), which was identified in our screen for genes upregulated after spinal cord injury, encode a protein belonging to the cAMP response element-binding protein (CREB)/ATF family of transcription factors. Our previous study showed that SCIRR69 functions as a transcriptional activator. However, the target gene regulated by SCIRR69 and its roles in injured neurons remain unknown. In this study, we showed that SCIRR69 is widely distributed in the central nervous system. Full-length SCIRR69 is an endoplasmic reticulum-bound protein. Following mechanical injury to neurons, SCIRR69 was induced and proteolytically cleaved by site-1 and site-2 proteases, and the proteolytically cleaved SCIRR69 (p60-SCIRR69) was translocated to the nucleus where it bound to brain-derived neurotrophic factor (BDNF) gene promoter II. In addition, loss- and gain-of-function studies confirmed that SCIRR69 is involved in the regulation of BDNF expression in injured neurons. As expected, the culture supernatants of PC12 cells stably expressing p60-SCIRR69 contained higher levels of BDNF, and more remarkably promoted neurite outgrowth in a spinal cord slice culture model in vitro than the supernatants of control cells. These results suggest that SCIRR69 is a novel regulator of the BDNF gene and may play an important role in the repair and/or regeneration of damaged neural tissues by specifically activating BDNF promoter II.

Peripheral toxicity in crack cocaine use disorders

A growing body of evidence suggests that crack cocaine misuse has widespread systemic and cognitive consequences, but little attention has been given to its systemic pathophysiology. We report here changes in inflammation markers, oxidative damage and brain derived neurotrophic factor in a sample of outpatients with crack cocaine use disorders. Fifty-three outpatients were recruited for this cross-sectional study and matched with fifty control subjects. The focus of this report is in between group differences in cytokines, oxidative damage and brain-derived neurotrophic factor (BDNF). Crack cocaine use was associated with higher BDNF levels when compared to controls, present only in those who used crack cocaine in the last month. Patients also had higher circulating levels of IL-1β, TNF-α and IL-10 when compared to controls. There were no significant differences in oxidative damage between patients and controls. These results represent a first demonstration that crack cocaine use disorders entail an activation of the reward, immune and inflammatory systems.

Reduced cocaine-seeking behavior in heterozygous BDNF knockout rats

Cocaine generates drug-seeking behavior by creating long-lasting changes in the reward pathway. The role of the growth factor, brain-derived neurotrophic factor (BDNF) in facilitating these changes was investigated in the present report with a genetic rat model. Using conditioned place preference, the current study investigated the hypothesis that a partial knockout of the BDNF gene in rats (BDNF+/−) would attenuate the rewarding effects of cocaine. Wildtype rats exposed to cocaine exhibited normal cocaine-seeking responses one day after conditioning and cocaine-seeking behavior was reinstated with drug priming following drug abstinence. In contrast, BDNF+/− rats did not show cocaine-seeking behavior one day after conditioning, nor did they respond to drug priming. A median split of rats based on BDNF levels in sera collected prior to behavioral procedures revealed that wildtype rats with high BDNF levels showed stronger conditioned place preference and reinstatement to cocaine. Together, the results support the hypothesis that a partial knockout of the BDNF gene attenuates the rewarding properties of cocaine. Additionally, individual differences in BDNF levels may predict future cocaine-seeking behavior. An underlying mechanism of these effects may be a reduction of the amount of synaptic changes made in the reward pathway.

Neural Stem-Like Cells Derived from Human Amnion Tissue are Effective in Treating Traumatic Brain Injury in Rat

Although human amnion derived mesenchymal stem cells (AMSC) are a promising source of stem cells, their therapeutic potential for traumatic brain injury (TBI) has not been widely investigated. In this study, we evaluated the therapeutic potential of AMSC using a rat TBI model. AMSC were isolated from human amniotic membrane and characterized by flow cytometry. After induction, AMSC differentiated in vitro into neural stem-like cells (AM-NSC) that expressed higher levels of the neural stem cell markers, nestin, sox2 and musashi, in comparison to undifferentiated AMSC. Interestingly, the neurotrophic factors, brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin 3 (NT-3), glial cell derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF) were markedly upregulated after neural stem cell induction. Following transplantation in a rat TBI model, significant improvements in neurological function, brain tissue morphology, and higher levels of BDNF, NGF, NT-3, GDNF and CNTF, were observed in the AM-NSC group compared with the AMSC and Matrigel groups. However, few grafted cells survived with minimal differentiation into neural-like cells. Together, our results suggest that transplantation of AM-NSC promotes functional rehabilitation of rats with TBI, with enhanced expression of neurotrophic factors a likely mechanistic pathway.

Alcohol, Brain Derived Neurotrophic Factor and Obesity among People Living with HIV.

IntroductionIn an expanding HAART era, obesity has become a health problem among persons living with HIV (PLWH). Whereas the rising level of obesity has been largely attributed to poor nutrition and exercise habits, differences in biological factors may explain why some individuals gain more weight than others. Thus, our main goal is to prospectively determine in PLWH whether plasma brain-derived neurotrophic factor (BDNF), and hazardous alcohol use (HAU), two overlooked but highly prevalent conditions among PLWH, correlate with an adverse anthropometric profile. Also to test whether these relationships varied in men and womenMethodsThe Platelets mediating Alcohol and HIV Damage Study (PADS) is an ongoing multiethnic study of 400 PLWH receiving regular medical care in South Florida (37% females and 63% males). Semi-annual visits consisted of a medical exam, including anthropometrics to assess both general (body mass index: BMI) and central obesity (waist and hip circumferences). Participants also completed health history questionnaires, and provided a fasting blood sample to obtain BDNF and immune and biochemical assessments.ResultsA sizable proportion of participants met the National Institutes of Health definition of overweight (BMI = 25–29.9 kg/m2; 26%) and obese (BMI ≥ 30 kg/m2; 35%). Women were more likely to be obese than men (OR=4.9, 95% CI=2.9–8.2, p=0.0001). Compared to men, women also exhibited the highest mean plasma BDNF levels (9,959 ± 6,578 vs. 7,470 ± 6,068 pg/ml, p=0.0001). Additional analyses indicated that HAU, particularly heavy drinkers, had the smallest waist and hip circumferences if they were males, but the opposite if they were females. High BDNF levels were positively correlated with BMI. Linear regression analysis revealed that gender, BDNF, and HAU were the best predictors of BMI.ConclusionIn summary, our findings offer novel insights into the relationships between BDNF, and alcohol use among overweight and obese PLWH. Our results also suggest that these relationships may be inherently different by gender.