A Novel Mutation in the MAP7D3 Gene in Two Siblings with Severe Intellectual Disability and Autistic Traits: Concurrent Assessment of BDNF Functional Polymorphism, X-Inactivation and Oxidative Stress to Explain Disease Severity.

Intellectual disabilities (ID) and autism spectrum disorders (ASD) are characterized by extreme genetic and phenotypic heterogeneity. However, understanding this heterogeneity is difficult due to the intricate interplay among multiple interconnected genes, epigenetic factors, oxidative stress, and environmental factors. Employing next-generation sequencing (NGS), we revealed the genetic cause of ID and autistic traits in two patients from a consanguineous family followed by segregation analysis. Furthermore, in silico prediction methods and 3D modeling were conducted to predict the effect of the variants. To establish genotype-phenotype correlation, X-chromosome inactivation using Methylation-specific PCR and oxidative stress markers were also investigated. By analyzing the NGS data of the two patients, we identified a novel frameshift mutation c.2174_2177del (p.Thr725MetfsTer2) in the MAP7D3 gene inherited from their mother along with the functional BDNF Val66Met polymorphism inherited from their father. The 3D modeling demonstrated that the p.Thr725MetfsTer2 variant led to the loss of the C-terminal tail of the MAP7D3 protein. This change could destabilize its structure and impact kinesin-1's binding to microtubules via an allosteric effect. Moreover, the analysis of oxidative stress biomarkers revealed an elevated oxidative stress in the two patients compared to the controls. To the best of our knowledge, this is the first report describing severe ID and autistic traits in familial cases with novel frameshift mutation c.2174_2177del in the MAP7D3 gene co-occurring with the functional polymorphism Val66M in the BDNF gene. Besides, our study underlines the importance of investigating combined genetic variations, X-chromosome inactivation (XCI) patterns, and oxidative stress markers for a better understanding of ID and autism etiology.

Assessment of suberoylanilide hydroxamic acid on a Alzheimer's disease model induced by ß-amyloid(1-42) in aged female mice: Neuromodulatory and epigenetic effect.

Alzheimer's disease (AD) is a neurodegenerative disease that affects several elderly people per years. AD is a pathology of multifactorial etiology, resulting from multiple environmental and genetic determinants. However, there is no effective pharmacological alternative for the treatment of this illness. In this sense, the purpose of current study was to characterize the mechanisms by which Aß1-42 injection via intracerebroventricular induces neurobehavioral changes in a time-course curve. In addition, suberoylanilide hydroxamic acid (SAHA) inhibitor of histone deacetylase (HDAC) was used to investigate the involvement of epigenetic modifications Aß1-42-caused in aged female mice. In general manner, Aß1-42 injection induced a major neurochemical disturbance in hippocampus and prefrontal cortex of animals and a serious impairment of memory. Overall, SAHA treatment attenuated neurobehavioral changes caused by Aß1-42 injection in aged female mice. The subchronic effects presented of SAHA were through modulation of HDAC activity, regulation of brain-derived neurotrophic factor (BDNF) levels and expression of BDNF mRNA, accompanied by unlocking cAMP/PKA/pCREB pathway in hippocampus and prefrontal cortex of animals.

Assessment of the relationship between Val66Met BDNF polymorphism and the effectiveness of gait rehabilitation in children and adolescents with cerebral palsy.

Cerebral palsy (CP) is associated with the non­progressive damage of upper motor neurons, which is manifested by a variety of symptoms, particularly motor and functional deficits. During the rehabilitation of patients with CP, attention is paid to improving mobility which can have a significant impact on the child's development. The effectiveness of rehabilitation depends on the plasticity of the nervous system, which may be genetically determined. Of importance are the various polymorphisms of the brain derived neurotrophic factor (BDNF) gene. It has been shown that the Val/Val genotype may predispose children to greater improvements in function and its maintenance. However, subjects with the Met allele showed a reduced tendency to improve their motor functions but had significantly better results on indirect tests assessing gait function. Fifty subjects with CP participated in this study. They were divided into two groups by genotype and examined on their rehabilitation progress in terms of improved gait function. The results correlated with other studies describing the relationship between the BDNF genotype and learning motor functions in CP, and with numerous studies on the relationship between BDNF genotype and neuroplasticity in stroke patients. This research provides a basis for the identification of genetic biomarkers in patients with CP which can be used to predict the effects of rehabilitation therapy and help with the development of personalized treatments.

Biochemical Mechanisms and Translational Relevance of Hippocampal Vulnerability to Distant Focal Brain Injury: The Price of Stress Response.

Focal brain injuries (in particular, stroke and traumatic brain injury) induce with high probability the development of delayed (months, years) cognitive and depressive disturbances which are frequently comorbid. The association of these complications with hippocampal alterations (in spite of the lack of a primary injury of this structure), as well as the lack of a clear dependence between the probability of depression and dementia development and primary damage severity and localization served as the basis for a new hypothesis on the distant hippocampal damage as a key link in the pathogenesis of cognitive and psychiatric disturbances. According to this hypothesis, the excess of corticosteroids secreted after a focal brain damage, in particular in patients with abnormal stress-response due to hypothalamic-pituitary-adrenal axis (HPAA) dysfunction, interacts with corticosteroid receptors in the hippocampus inducing signaling pathways which stimulate neuroinflammation and subsequent events including disturbances in neurogenesis and hippocampal neurodegeneration. In this article, the molecular and cellular mechanisms associated with the regulatory role of the HPAA and multiple functions of brain corticosteroid receptors in the hippocampus are analyzed. Functional and structural damage to the hippocampus, a brain region selectively vulnerable to external factors and responding to them by increased cytokine secretion, forms the basis for cognitive function disturbances and psychopathology development. This concept is confirmed by our own experimental data, results of other groups and by prospective clinical studies of post-stroke complications. Clinically relevant biochemical approaches to predict the risks and probability of post-stroke/post-trauma cognitive and depressive disturbances are suggested using the evaluation of biochemical markers of patients' individual stress-response. Pathogenetically justified ways for preventing these consequences of focal brain damage are proposed by targeting key molecular mechanisms underlying hippocampal dysfunction.

Assessment of genes involved in behavior, learning, memory, and synaptic plasticity following status epilepticus in rats.

OBJECTIVE: In this study, it was aimed to evaluate cognitive and behavioral changes after status epilepticus (SE) induced by pentylenetetrazole in immature rats via Morris water maze and open-field area tests and to assess alterations in expression of 84 key genes involved in synaptic plasticity after SE. METHOD: The study was conducted on 30 immature rats (12-days old). The rats were assigned into groups as control and experiment (SE) groups. The SE was induced by pentylenetetrazole in 12-days old rats. In addition, experiment group was divided into two groups as mature (n = 8) and immature SE (n = 8) subgroups. Again, the control group was divided into two groups as mature (n = 7) and immature control (n = 7) subgroups. Hippocampal tissue samples were prepared, and expression of 84 key genes involved in synaptic plasticity was assessed in Genome and Stem Cell Center of Erciyes University before behavioral tests in immature rats (22-days old) and after open-filed area and Morris water maze tests in mature rats (72-days old) in both experiment and control groups. RESULTS: No significant difference was detected in behavioral tests assessing spatial memory and learning among groups. Significant differences were detected, ARC (activity-regulated cytoskeleton-associated protein), BDNF (brain-derived neurotrophic factor), MAPK1 (mitogen-activated protein kinase 1), NR4A1 (nuclear receptor subfamily 4 group A member 1), PPP3CA (protein phosphatase 3 catalytic subunit alpha), RGS2 (regulator of G protein signaling 2), and TNF (tumor necrosis factor) gene expressions between control and experiment groups in immature rats whereas in ADCY8 (adenylate cyclase 8), BDNF (brain-derived neurotrophic factor), EGR4 (early growth response 4), and KIF17 (kinesin family member 17) gene expressions between control and experiment groups in mature rats. DISCUSSION: In this study, differences detected in gene expressions of synaptic plasticity after SE indicate in which steps of synaptic plasticity may be problematic in epileptogenesis. The gene expressions in this study may be considered as potential biomarkers; however, epileptogenesis is a dynamic process and cannot be explained through a single mechanism. Future studies on epileptogenesis and studies specifically designed to evaluate genes detected in our study will further elucidate synaptic plasticity in epilepsy and epileptogenesis.

Chaihu-Shugan-San and absorbed meranzin hydrate induce anti-atherosclerosis and behavioral improvements in high-fat diet ApoE-/- mice via anti-inflammatory and BDNF-TrkB pathway.

The comorbidity of coronary heart disease (CHD) and depression in patients is extremely prevalent, with a rate from 20 to 50%, while depression-like behaviors exist in a larger percentage of patients. Therefore, the study of comorbidities is particularly urgent. Chaihu-Shugan-San (CSS), a classical traditional Chinese medicine formula, has been used to treat CHD with depression for hundreds of years. However, the mechanism of its action on comorbidities remains unclear. Here, we focused on the behavioral changes in ApoE-/- mice fed a high-fat diet (HFD) and elucidated the mechanism of CSS and its main absorbed component, meranzin hydrate (MH), as an anti-atherosclerosis and anti-depression agent. In the present study, mice were fed an HFD for 16 weeks and were intragastrically administered high and low doses of CSS and MH. Depressive-like behaviors were evaluated by the sucrose preference test, the open-field test, the light-dark test and the tail-suspension test, after which atherosclerotic plaques, plasma lipids, inflammatory cytokine levels and the expression of BDNF/TrkB were measured. We demonstrated that the atherosclerosis model group exhibited significant depressant behaviors. Moreover, CSS inhibited depressive-like behavioral changes, reduced atherosclerotic plaque areas, plasma total cholesterol, triglycerides, LDL-cholesterol levels and inflammatory cytokines including TNF-α, IL-1ß, and IL-6 in plasma and hippocampi, increased the protein and mRNA expression of BDNF and TrkB in the aorta and the hippocampus. Interestingly, MH, the main component in CSS that is absorbed in the plasma and hippocampus, exerted effects similar to those of CSS. In addition, MH increased the protein and mRNA expression of BDNF and TrkB in human umbilical vein endothelial cells (HUVECs) induced by LPS. Collectively, these results suggest that MH represents the CSS decoction, induces anti-atherosclerosis effects and improves depression-like behaviors in HFD-fed ApoE-/- mice. Moreover, the regulation of proinflammatory factors and BDNF-TrkB signaling are possibly involved in this process. Our findings indicate that MH is a potential phytochemical compound for the prevention of the comorbidity of atherosclerosis and depression.

Assessment of the key regulatory genes and their Interologs for Turner Syndrome employing network approach.

Turner Syndrome (TS) is a condition where several genes are affected but the molecular mechanism remains unknown. Identifying the genes that regulate the TS network is one of the main challenges in understanding its aetiology. Here, we studied the regulatory network from manually curated genes reported in the literature and identified essential proteins involved in TS. The power-law distribution analysis showed that TS network carries scale-free hierarchical fractal attributes. This organization of the network maintained the self-ruled constitution of nodes at various levels without having centrality-lethality control systems. Out of twenty-seven genes culminating into leading hubs in the network, we identified two key regulators (KRs) i.e. KDM6A and BDNF. These KRs serve as the backbone for all the network activities. Removal of KRs does not cause its breakdown, rather a change in the topological properties was observed. Since essential proteins are evolutionarily conserved, the orthologs of selected interacting proteins in C. elegans, cat and macaque monkey (lower to higher level organisms) were identified. We deciphered three important interologs i.e. KDM6A-WDR5, KDM6A-ASH2L and WDR5-ASH2L that form a triangular motif. In conclusion, these KRs and identified interologs are expected to regulate the TS network signifying their biological importance.

Assessment of Brain Derived Neurotrophic Factor in hair to study stress responses: A pilot investigation.

To study pathogenic stress-effects in health and disease, it is paramount to define easy access parameters for non-invasive analysis of biological change in response to stress. Hair samples successfully provide this access for the study of hypothalamus-pituitary-adrenal axis (HPA) changes. In this study, we assess the hair expression and corresponding epigenetic changes of a neurotrophin essential for autonomic nervous system function and mental health: brain derived neurotrophic factor (BDNF). In three independent studies in healthy academic volunteers (study I: German students, N=36; study II, German academic population sample, N=28; study III: Mexican students, N=115), BDNF protein expression or BDNF gene (BDNF) histone acetylation was determined. Simultaneously, mental distress and distress-associated somatic complaints were assessed by self-report. In study I, we found a negative correlation between hair-BDNF protein level and hair-cortisol as well as between hair-BDNF and somatic complaints, while hair-cortisol correlated positively with mental distress. In study II, we found a negative correlation between H4 histone acetylation at the BDNF gene P4-promoter and somatic complaints. Regression analysis confirmed confounder stability of associations in both studies. In study III, we confirmed study I and found lower hair-BDNF protein level in volunteers with high somatic complaints, who also reported higher mental distress during the end of term exams. The results indicate that BDNF protein levels can be detected in clipped hair and are associated with somatic complaints and stress in life. In addition, we concluded that plucked hair can provide material for the study of epigenetic changes in stress-affected tissues. These tools can prove valuable for future studies on distress, both under experimental and field conditions.

Exploring the association between BDNF Val66Met polymorphism and suicidal behavior: Meta-analysis and systematic review.

Suicide is a serious worldwide health problem of critical consequences. Nowadays genetic factors are considered to be an important cause of suicide. The association between Val66Met (rs6265) polymorphism of the BDNF gene and suicide behavior has been increasingly studied. The aim of this study was to perform a meta-analysis in order to unravel the possible association between BDNF gene Val66Met polymorphism and suicide behavior. These meta-analysis and systematic review were performed using 23 articles that searched for a genetic association between Val66Met and suicide behavior, including 4532 cases and 5364 control subjects. The association was analyzed following the models: allelic, homozygous, heterozygous, dominant and recessive. Also, analyses by ethnicity (Caucasian and Asian populations) were done following the same four models. When the overall population was evaluated, we found no evidence of association between the polymorphism Val66Met of BDNF (rs6265) and suicide behavior (Met vs. Val: OR: 1.01; 95% CI = 0.92-1.10). However, a significant increased risk was found in the subgroup analysis by ethnicity in Caucasian populations (Met-Met vs. Met-Val + Val-Val: OR: 1.96; 95% CI = 1.58-2.43) and Asian populations (Val-Val vs. Val-Met + Met: OR: 1.36; 95% CI = 1.04-1.78). Our results suggest there is no association between the BDNF gene Val66Met (rs6265) and suicide behavior in the overall population. However, ethnic differences can be observed and the BDNF Val66Met might increase the risk for suicide behavior in Asian and Caucasian populations. Further studies with larger samples are necessary in order to have conclusive outcomes.

First Insights into Human Fingertip Regeneration by Echo-Doppler Imaging and Wound Microenvironment Assessment.

Fingertip response to trauma represents a fascinating example of tissue regeneration. Regeneration derives from proliferative mesenchymal cells (blastema) that subsequently differentiate into soft and skeletal tissues. Clinically, conservative treatment of the amputated fingertip under occlusive dressing can shift the response to tissue loss from a wound repair process towards regeneration. When analyzing by Immunoassay the wound exudate from occlusive dressings, the concentrations of brain-derived neurotrophic factor (BDNF) and leukemia inhibitory factor (LIF) were higher in fingertip exudates than in burn wounds (used as controls for wound repair versus regeneration). Vascular endothelial growth factor A (VEGF-A) and platelet-derived growth factor (PDGF) were highly expressed in both samples in comparable levels. In our study, pro-inflammatory cytokines were relatively higher expressed in regenerative fingertips than in the burn wound exudates while chemokines were present in lower levels. Functional, vascular and mechanical properties of the regenerated fingertips were analyzed three months after trauma and the data were compared to the corresponding fingertip on the collateral uninjured side. While sensory recovery and morphology (pulp thickness and texture) were similar to uninjured sides, mechanical parameters (elasticity, vascularization) were increased in the regenerated fingertips. Further studies should be done to clarify the importance of inflammatory cells, immunity and growth factors in determining the outcome of the regenerative process and its influence on the clinical outcome.

Association of Brain-Derived Neurotrophic Factor G196A and Attempted Suicide: A Case-Control Study in Rural China.

BACKGROUND: Suicide is an important public problem, the mechanism of which has not been clarified. Many studies have focused on the molecular, biological and genetic mechanisms of suicide. Brain-derived neurotrophic factor (BDNF) G196A is one of the most leading loci in recent studies, but the results are inconsistent. METHODS: We conducted a 1:1 age- and sex-matched case-control study in rural areas of Shandong Province, China. A total of 365 pairs of cases and controls were finally recruited into our study. The adjusted odds ratios (AORs) of BDNF 196G/G and their 95% confidence intervals (CIs) were calculated by multivariate conditional logistic regression models. RESULTS: No association between BDNF polymorphisms and attempted suicide was found in the overall population. However, the BDNF 196G/G genotype was significantly related to attempted suicide in the elderly population (AOR = 7.85, 95% CI: 1.12-54.90, p = 0.038), while the associations were not significant in young and middle-aged groups. CONCLUSION: Our study suggests that the BDNF 196G/G genotype increases the risk of attempted suicide in elderly people.

Development of a cost-efficient novel method for rapid, concurrent genotyping of five common single nucleotide polymorphisms of the brain derived neurotrophic factor (BDNF) gene by tetra-primer amplification refractory mutation system.

Brain derived neurotrophic factor (BDNF) is a molecular trophic factor that plays a key role in neuronal survival and plasticity. Single nucleotide polymorphisms (SNPs) of the BDNF gene have been associated with specific phenotypic traits in a large number of neuropsychiatric disorders and the response to psychotherapeutic medications in patient populations. Nevertheless, due to study differences and occasionally contrasting findings, substantial further research is required to understand in better detail the association between specific BDNF SNPs and these psychiatric disorders. While considerable progress has been made recently in developing advanced genotyping platforms of SNPs, many high-throughput probe- or array-based detection methods currently available are limited by high costs, slow processing times or access to advanced instrumentation. The polymerase chain reaction (PCR)-based, tetra-primer amplification refractory mutation system (T-ARMS) method is a potential alternative technique for detecting SNP genotypes efficiently, quickly, easily, and cheaply. As a tool in psychopathology research, T-ARMS was shown to be capable of detecting five common SNPs in the BDNF gene (rs6265, rs988748, rs11030104, 11757G/C and rs7103411), which are all SNPs with previously demonstrated clinical relevance to schizophrenia and depression. The present technique therefore represents a suitable protocol for many research laboratories to study the genetic correlates of BDNF in psychiatric disorders. Copyright Copyright © 2015 John Wiley & Sons, Ltd.

Discrete BDNF Neurons in the Paraventricular Hypothalamus Control Feeding and Energy Expenditure.

Brain-derived neurotrophic factor (BDNF) is a key regulator of energy balance; however, its underlying mechanism remains unknown. By analyzing BDNF-expressing neurons in paraventricular hypothalamus (PVH), we have uncovered neural circuits that control energy balance. The Bdnf gene in the PVH was mostly expressed in previously undefined neurons, and its deletion caused hyperphagia, reduced locomotor activity, impaired thermogenesis, and severe obesity. Hyperphagia and reduced locomotor activity were associated with Bdnf deletion in anterior PVH, whereas BDNF neurons in medial and posterior PVH drive thermogenesis by projecting to spinal cord and forming polysynaptic connections to brown adipose tissues. Furthermore, BDNF expression in the PVH was increased in response to cold exposure, and its ablation caused atrophy of sympathetic preganglionic neurons. Thus, BDNF neurons in anterior PVH control energy intake and locomotor activity, whereas those in medial and posterior PVH promote thermogenesis by releasing BDNF into spinal cord to boost sympathetic outflow.

[Animal Models of Depression: Behavior as the Basis for Methodology, Assessment Criteria and Classifications].

Analysis of the current state modeling of depression in animals is presented. Criteria and classification systems of the existing models are considered as well as approaches to the assessment of model validity. Though numerous approaches to modeling of depressive states based on disturbances of both motivational and emotional brain mechanisms have been elaborated, no satisfactory model of stable depression state has been developed yet. However, the diversity of existing models is quite positive since it allows performing targeted studies of selected neurobiological mechanisms and laws of depressive state development, as well as to investigate mechanisms of action and predict pharmacological profiles of potential antidepressants.

Altered DNA methylation status of human brain derived neurotrophis factor gene could be useful as biomarker of depression.

Brain-derived neurotrophic factor (BDNF) is involved in the survival, development, and synaptic plasticity of neurons. BDNF is believed to be associated with the pathophysiology of psychiatric disorders. Several studies have suggested the relevance of DNA methylation in its promoter region with depression. Here, we report different methylation statuses in groups with different depressive scores or undergoing different levels of job-stress. DNA samples were extracted from the saliva of 774 Japanese workers, and the methylation status was determined using the Illumina HumanMethylation 450 K Microarray. Depressive symptoms were measured using the Kessler's K6 questionnaire. Job-stress scales were assessed via a self-administered questionnaire. Independent DNA pools were formed based on K6 and job-strain scores, and the methylation levels were compared among these pools. The average DNA methylation rate was significantly decreased in the highest K6 score group compared to the lowest group (methylated signals, 14.2% vs. 16.5%, P = 2 · 16 × 10(-198)). This difference remained for the CpG island in the promoter region (10.4% vs. 5.8%, P = 3 · 67 × 10(-133)). Regarding the job-strain score, there was a slight increase in the methylation level of the whole gene in the group with the highest score compared to that with the lowest score; however, these groups showed no difference in the promoter region. Our results revealed significant changes in the DNA methylation status of the complete human BDNF gene in persons with depression compared to normal individuals, especially in the promoter region of exon 1. This indicates that DNA methylation in this gene is a promising biomarker for diagnosing depression.

Reducing aggression and impulsivity through school-based prevention programs: a gene by intervention interaction.

A variety of school-based, universal preventive interventions have been developed to address behavioral and mental health problems. Unfortunately, few have been evaluated within the context of randomized controlled trials with long-term follow-up. Even fewer still have examined the potential genetic factors that may drive differential impact of the intervention. In the present analysis, we examine the extent to which the longitudinal effects of two elementary school-based interventions were moderated by the brain-derived neurotrophic factor (BDNF) gene, which has been linked with aggression and impulsive behaviors. The sample included 678 urban, primarily African American children who were randomly assigned along with their teachers to one of three first grade classroom conditions: classroom-centered (CC) intervention, Family School Partnership (FSP), or a control condition. The teacher ratings of the youth's aggressive and impulsive behavior were obtained at baseline and in grades 6-12. Single-nucleotide polymorphisms (SNPs) from the BDNF gene were extracted from the genome-wide data. Longitudinal latent trait-state-error models indicated a significant interaction between a particular profile of the BDNF SNP cluster (46 % of sample) and CC intervention on impulsivity (ß = -.27, p < .05). A similar interaction was observed for the BDNF SNP cluster and the CC intervention on aggression (ß = -.14, p < .05). The results suggest that the impacts of preventive interventions in early elementary school on late adolescent outcomes of impulsivity and aggression can be potentially modified by genetic factors, such as BDNF. However, replication of these results is necessary before firm conclusions can be drawn.

A unified GMDR method for detecting gene-gene interactions in family and unrelated samples with application to nicotine dependence.

Gene-gene and gene-environment interactions govern a substantial portion of the variation in complex traits and diseases. In convention, a set of either unrelated or family samples are used in detection of such interactions; even when both kinds of data are available, the unrelated and the family samples are analyzed separately, potentially leading to loss in statistical power. In this report, to detect gene-gene interactions we propose a generalized multifactor dimensionality reduction method that unifies analyses of nuclear families and unrelated subjects within the same statistical framework. We used principal components as genetic background controls against population stratification, and when sibling data are included, within-family control were used to correct for potential spurious association at the tested loci. Through comprehensive simulations, we demonstrate that the proposed method can remarkably increase power by pooling unrelated and offspring's samples together as compared with individual analysis strategies and the Fisher's combining p value method while it retains a controlled type I error rate in the presence of population structure. In application to a real dataset, we detected one significant tetragenic interaction among CHRNA4, CHRNB2, BDNF, and NTRK2 associated with nicotine dependence in the Study of Addiction: Genetics and Environment sample, suggesting the biological role of these genes in nicotine dependence development.

BDNF Val(66)Met genotype is associated with drug-seeking phenotypes in heroin-dependent individuals: a pilot study.

Brain-derived neurotrophic factor (BDNF) Val(66)Met genotype has been associated with neurobehavioral deficits. To examine its relevance for addiction, we examined BDNF genotype differences in drug-seeking behavior. Heroin-dependent volunteers (n = 128) completed an interview that assessed past-month naturalistic drug-seeking/use behaviors. In African Americans (n = 74), the Met allele was uncommon (carrier frequency 6.8%); thus, analyses focused on European Americans (n = 54), in whom the Met allele was common (carrier frequency 37.0%). In their natural setting, Met carriers (n = 20) reported more time- and cost-intensive heroin-seeking and more cigarette use than Val homozygotes (n = 34). BDNF Val(66)Met genotype predicted 18.4% of variance in 'weekly heroin investment' (purchasing time × amount × frequency). These data suggest that the BDNF Met allele may confer a 'preferred drug-invested' phenotype, resistant to moderating effects of higher drug prices and non-drug reinforcement. These preliminary hypothesis-generating findings require replication, but are consistent with pre-clinical data that demonstrate neurotrophic influence in drug reinforcement. Whether this genotype is relevant to other abused substances besides opioids or nicotine, or treatment response, remains to be determined.

[The preparation and bioactivity assessment of gene recombinant fibrin-binding brain derived neurotrophic factor].

Using the E. coli, we fabricated the gene reconstructed brain derived neurotrophic factor with a fibrin binding domain (FBD-BDNF). We then tested the neurotrophic bioactivity and fibrin-binding ability of the FBD-BDNF. The E. coli was used to express the recombinant protein. The inclusion body was purified with column chromatography and renaturated to construct the right 3D formation. In this study, we successfully fabricated the FBD-BDNF and tested the binding ability and neurotrophic activity. The results demonstrated that FBD-BDNF had special binding ability of fibrin and significant neurotrophic activity for DRG cells. FBD-BDNF could have a promising application prospect in nerve tissue engineering.

The study of candidate genes related to the neurodevelopmental hypothesis of anorexia nervosa: classical association study versus decision tree.

In this research, we conducted a study of genes connected with the neurodevelopmental hypothesis of anorexia nervosa, using classical statistical and data-mining methods to establish a relationship with disease risk and algorithms to identify the best genetic predictors of anorexia nervosa.