Investigating neurotrophin genetics and hippocampal volume

As individuals get older, the structural integrity of brain regions becomes progressively diminished. Neurotrophic function might aid in preventing such losses through increased synaptogenesis and neurogenesis, particularly in the hippocampus, a brain structure relevant for cognitive function. However, the carriage of certain genetic alleles for genes involved in neurotrophic function might restrain the effectiveness of neurotrophin signalling, hindering neuroprotection. Yet, research on the contribution of single nucleotide polymorphisms (SNPs) within genes coding for neurotrophins and their receptors to hippocampal volumes is scarce, with the exception of rs6265 within the brain-derived neurotrophic factor gene. Therefore, the aim of this study was to identify SNPs within genes involved neurotrophic function that are associated with hippocampal volume in a sample of 23,776 cognitively normal older adults from the UK Biobank. We found that, in individuals older than 50, homozygote carriage of the major alleles rs4839435-A within nerve growth factor gene and rs56405676-T within the neurotrophic receptor tyrosine kinase 2 gene, were associated with increase hippocampal volumes, compared to carriage of 1 or 2 copies of the minor alleles. However, only rs56405676-T was significantly associated with greater hippocampal volumes in individuals older than 60. Hence this study might serve to identify populations at higher risk of hippocampal attrition and cognitive decline.

A R2R3-MYB Transcription Factor Gene, BpMYB123, Regulates BpLEA14 to Improve Drought Tolerance in Betula platyphylla

Drought stress causes various negative impacts on plant growth and crop production. R2R3-MYB transcription factors (TFs) play crucial roles in the response to abiotic stress. However, their functions in Betula platyphylla haven’t been fully investigated. In this study, a R2R3 MYB transcription factor gene, BpMYB123, was identified from Betula platyphylla and reveals its significant role in drought stress. Overexpression of BpMYB123 enhances tolerance to drought stress in contrast to repression of BpMYB123 by RNA interference (RNAi) in transgenic experiment. The overexpression lines increased peroxidase (POD) and superoxide dismatase (SOD) activities, while decreased hydrogen peroxide (H2O2), superoxide radicals (O2–), electrolyte leakage (EL) and malondialdehyde (MDA) contents. Our study showed that overexpression of BpMYB123 increased BpLEA14 gene expression up to 20-fold due to BpMYB123 directly binding to the MYB1AT element of BpLEA14 promoter. These results indicate that BpMYB123 acts as a regulator via regulating BpLEA14 to improve drought tolerance in birch.

The effect of brain neurotrophic factor gene polymorphism on the effectiveness of therapeutic and rehabilitation measures in patients with psychostimulant dependence

Justification. Along with the rising consumption of psychostimulants, the number of patients with dependence on psychostimulants is increasing all over the world and in Russia in particular. At the same time, the number of patients with dependence on drug combinations is increasing, most of which are psychostimulants. Aim. The aim of the work is to develop a personalized approach to the therapy of patients with dependence on psychostimulants, taking into account the polymorphism of the neurotrophic factor gene of the brain. Material and methods. 305 patients with dependence on psychostimulants, men and women from 18 to 50 years old, were studied. Depending on the drug used and their combinations, as well as the presence of comorbid psychiatric pathology, all patients were divided into 6 groups. Research methods: molecular-genetic, clinical-psychopathological, catamnestic, statistical (parametric and nonparametric methods using Statistica 10.0 programs of STAT Soft Inc., USA). The effect of polymorphism of the neurotrophic factor gene of the brain on the effectiveness of therapeutic and rehabilitation measures in patients in different groups was evaluated. Results. It was found that patients who use only psychostimulants and psychostimulants with cannabinoids, having a homozygous (GG) genotype of the neurotrophic factor gene of the brain, are longer in the rehabilitation program and have the longest remissions. Conclusion. Polymorphism of the neurotrophic factor gene of the brain affects the effectiveness of therapeutic and rehabilitation measures in patients with dependence on psychostimulants.

Cognitive Development and Brain Gray Matter Susceptibility to Prenatal Adversities: Moderation by the Prefrontal Cortex Brain-Derived Neurotrophic Factor Gene Co-expression Network

Background: Previous studies focused on the relationship between prenatal conditions and neurodevelopmental outcomes later in life, but few have explored the interplay between gene co-expression networks and prenatal adversity conditions on cognitive development trajectories and gray matter density.Methods: We analyzed the moderation effects of an expression polygenic score (ePRS) for the Brain-derived Neurotrophic Factor gene network (BDNF ePRS) on the association between prenatal adversity and child cognitive development. A score based on genes co-expressed with the prefrontal cortex (PFC) BDNF was created, using the effect size of the association between the individual single nucleotide polymorphisms (SNP) and the BDNF expression in the PFC. Cognitive development trajectories of 157 young children from the Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN) cohort were assessed longitudinally in 4-time points (6, 12, 18, and 36 months) using the Bayley-II mental scales.Results: Linear mixed-effects modeling indicated that BDNF ePRS moderates the effects of prenatal adversity on cognitive growth. In children with high BDNF ePRS, higher prenatal adversity was associated with slower cognitive development in comparison with those exposed to lower prenatal adversity. Parallel-Independent Component Analysis (pICA) suggested that associations of expression-based SNPs and gray matter density significantly differed between low and high prenatal adversity groups. The brain IC included areas involved in visual association processes (Brodmann area 19 and 18), reallocation of attention, and integration of information across the supramodal cortex (Brodmann area 10).Conclusion: Cognitive development trajectories and brain gray matter seem to be influenced by the interplay of prenatal environmental conditions and the expression of an important BDNF gene network that guides the growth and plasticity of neurons and synapses.

von Willebrand Factor Gene Polymorphism in Preeclampsia Pregnant at Medan, Indonesia

BACKGROUND: von Willebrand Factor (vWF) is a large glycoprotein mediating hemostasis and thrombosis. The roles of vWF are platelets adhesion to sites of vascular damage and stabilization of coagulation factor VIII. AIM: This study aimed to analyze the polymorphism of the vWF gene on preeclampsia (PE) in pregnancy in Medan, Indonesia. MATERIALS AND METHODS: DNA was amplified using the polymerase chain reaction and was electrophoresed in agarose 2%. Electrophoresis results were detected using Gel Doc 1000 (Biorad, USA). The sequencing method was used to identify polymorphism from vWF gene. RESULTS: From 50 samples of PE patients, the g.93308C>T vWF gene polymorphism was found with the percentage of TT, CT, and CC genotypes as 50%, 42%, and 8%, respectively. CONCLUSION: The c.93308C>T vWF gene polymorphism was found in the genotype percentage of homozygous TT, and heterozygote CT was greater than wild-type CC.

Transcription Factor Gene Pea3 Regulates Erectile Function in Mice

Background: Male mice with homozygous loss of function mutations of the ETS transcription factor gene Pea3 (Pea3 null) are infertile due to their inability to deposit semen plugs, however the specific deficits in male sexual behaviors that drive this phenotype are unknown. Aim: To investigate the regulatory role of the Pea3 gene in organizing gross sexual behaviors and erectile functioning during active copulation. Methods: The copulatory behavior of male mice (Pea3 null and control) with hormonally primed ovariectomized females was monitored via high-speed and high-resolution digital videography to assess for differences in female-directed social behaviors, gross sexual behaviors (mounting, thrusting), and erectile and ejaculatory function. Outcomes: Pea3 null male mice have dramatically reduced erectile function during sexual intercourse, however other aspects of male sexual behaviors are largely intact. Results: Pea3 null male mice exhibit greatly reduced erectile function, with 44% of males displaying no visible erections during mounting behaviors, and none achieving sustained erections. As such, Pea3 null males are incapable of intromission, and semen plug deposition, despite displaying largely normal female-directed social behaviors, mounting behaviors, and ejaculatory grasping behavior. Additionally, the coordination of the timing of thrusting trains is impaired in Pea3 null males. Clinical Implications: The identification of the transcription factor Pea3 in regulating erectile function in mice may provide a useful target for understanding the genetics of male sexual dysfunction in human patients. Strengths and Limitations: High-speed and high-resolution videography allows for a detailed analysis of male sexual behaviors and erectile functioning in Pea3 null and control mice. How disruption of the Pea3 gene translates to erectile dysfunction is still unknown. Conclusion: The transcription factor gene Pea3 regulates the ability to achieve and maintain erections in male mice.

OsIAA18, an Aux/IAA Transcription Factor Gene, Is Involved in Salt and Drought Tolerance in Rice

Auxin/indoleacetic acid (Aux/IAA) proteins play an important regulatory role in the developmental process of plants and their responses to stresses. A previous study has shown that constitutive expression of OsIAA18, an Aux/IAA transcription factor gene of rice improved salt and osmotic tolerance in transgenic Arabidopsis plants. However, little work is known about the regulatory functions of the OsIAA18 gene in regulating the abiotic stress tolerance of rice. In this study, the OsIAA18 gene was introduced into the rice cultivar, Zhonghua 11 and the OsIAA18 overexpression in rice plants exhibited significantly enhanced salt and drought tolerance compared to the wild type (WT). Moreover, overexpression of OsIAA18 in rice increased endogenous levels of abscisic acid (ABA) and the overexpression of OsIAA18 in rice plants showed hypersensitivity to exogenous ABA treatment at both the germination and postgermination stages compared to WT. Overexpression of OsIAA18 upregulated the genes involved in ABA biosynthesis and signaling pathways, proline biosynthesis pathway, and reactive oxygen species (ROS)-scavenging system in the overexpression of OsIAA18 in rice plants under salt and drought stresses. Proline content, superoxide dismutase (SOD), and peroxidase (POD) activities were significantly increased, whereas malonaldehyde (MDA), hydrogen peroxide (H2O2), and superoxide anion radical (O2–) content were significantly decreased in the transgenic plants under salt and drought stresses. Taken together, we suggest that OsIAA18 plays a positive role in drought and salt tolerance by regulating stress-induced ABA signaling. The OsIAA18 gene has a potential application in genetically modified crops with enhanced tolerance to abiotic stresses.