Striatal Dopamine Level Contributes to Hydroxyl Radical Generation and Subsequent Neurodegeneration in the Striatum in 3-nitropropionic Acid-Induced Huntington’s Disease in Rats

We tested the hypothesis that dopamine contributes significantly to the hydroxyl radical (�OH)-induced striatal neurotoxicity caused by 3-nitropropionic acid (3-NP) in a rat model of Huntington’s disease. Dopamine (10–100 mM) or 3-NP (10–1000 mM) individually caused a significant increase in the generation of hydroxyl radical (�OH) in themitochondria, which was synergistically enhanced when the lowest dose of the neurotoxin (10 mM) and dopamine (100 mM) were present together. Similarly, systemic administration of L-DOPA (100–250 mg/kg) and a low dose of 3-NP (10 mg/kg) potentiated �OH generation in the striatum, and the rats exhibited significant decrease in stride length, a direct indication of neuropathology. The pathology was also evident in striatal sections subjected to NeuN immunohistochemistry. The significant changes in stride length, the production of striatal �OH and neuropathological features due to administration of a toxic dose of 3-NP (20 mg/kg) were significantly attenuated by treating the rats with tyrosine hydroxylase inhibitor a-methyl-p-tyrosine prior to 3-NP administration. These results strongly implicate a major contributory role of striatal dopamine in increased generation of �OH, which leads to striatal neurodegeneration and accompanied behavioral changes, in 3-NP model of Huntington’s disease

Attention deficit-hyperactivity disorder suffers from mitochondrial dysfunction

Background: Pathophysiology of attention-deficit hyperactivity disorder (ADHD) is not known, and therefore the present study investigated mitochondrial defects, if any in cybrids created from patients and control population. Methods: To investigate mitochondrial pathology in ADHD, cybrids cell lines were created from ADHD probands and controls by fusing their platelets with ρ0-cells prepared from SH-SY5Y neuroblastoma cell line. Cellular respiration, oxidative stress, mitochondrial membrane potential and morphology were evaluated employing oxygraph, mitochondria-specific fluorescence staining and evaluation by FACS, and immunocytochemistry. HPLC-electrochemical detection, quantitative RT-PCR and Blue Native PAGE were employed respectively for assays of serotonin, mitochondrial ATPase 6/8 subunits levels and complex V activity. Results: Significantly low cellular and mitochondrial respiration, ATPase6/8 transcripts levels, mitochondrial complex V activity and loss of mitochondrial membrane potential and elevated oxidative stress were observed in ADHD cybrids. Expression of monoamine oxidizing mitochondrial enzymes, MAO-A and MAO-B levels remained unaffected. Two-fold increase in serotonin level was noted in differentiated cybrid-neurons. Conclusions: Since cybrids are shown to replicate mitochondrial defects seen in post-mortem brains, these observed defects in ADHD cybrids strongly suggest mitochondrial pathology in this disorder. General significance: Mitochondrial defects are detected in ADHD cybrids created from patients' platelets, implying bioenergetics crisis in the mitochondria could be a contributory factor for ADHD pathology and/or phenotypes

Serotonin transporter promoter variants: analysis in Indian autistic and control population

Serotonin transporter (5-HTT) is a transmembrane protein belonging to Na<SUP>+</SUP>/Cl<SUP>−</SUP> dependent membrane transporter family and transports 5-HT across the membranes of presynaptic neurons. 5-HTT-linked polymorphic region (5-HTTLPR) gained much interest because of the differential regulation of expression and activity of 5-HTT by its various genotypes. A population-based study has been conducted on 5-HTTLPR with 358 individuals, which included 79 autistic probands, 136 parents, and 143 controls from two subpopulations of east and northeast regions of India. The genotypic frequencies of all the groups conform to Hardy–Weinberg equilibrium. With the finding of efficacy of serotonin reuptake inhibitors in ameliorating ritualistic behavior in autistic disorder, 5-HTT emerged as a putative candidate gene for autism and association studies have been carried out in different ethnic populations. But these studies were inconclusive due to conflicting results on association. Because such a study has never been performed in the Indian population, we have tested the possible involvement of 5-HTTLPR polymorphism with autism. The present study failed to establish any association or linkage of 5-HTTLPR with autism in the Indian population by case–control studies (&#x03A7;<SUP>2</SUP> = 1.314, P = 0.63) and family-based approaches (TDT &#x03A7;<SUP>2</SUP> = 0.22, P = 0.64 and HHRR-&#x03A7;<SUP>2</SUP> = 0.25, P = 0.61). However, when a meta-analysis of all the available TDT data, inclusive of the present study is carried out, we observed a significant preferential transmission of S-allele from parents to the affected offspring (&#x03A7;<SUP>2</SUP> = 7.51, P = 0.006) indicating an association of 5-HTTLPR with autism

Pilot study indicate role of preferentially transmitted monoamine oxidase gene variants in behavioral problems of male ADHD probands

Abstract Background Attention deficit hyperactivity disorder (ADHD) is an etiologically complex childhood onset neurobehavioral disorder characterized by age-inappropriate inattention, hyperactivity, and impulsivity. Symptom severity varies widely and boys are diagnosed more frequently than girls. ADHD probands were reported to have abnormal transmissions of dopamine, serotonin, and/or noradrenaline. Monoamine oxidase A (MAOA) and B (MAOB), mitochondrial outer membrane bound two isoenzymes, mediate degradation of these neurotransmitters and thus regulating their circulating levels. Case-control analyses in different populations, including Indians, suggested involvement of MAOA and MAOB genes in the etiology of ADHD. Due to high heritability rate of ADHD, we tested familial transmission of MAOA and MAOB variants to ADHD probands in 190 nuclear families having ADHD probands from Indo-Caucasoid ethnicity. Methods Subjects were recruited following the Diagnostic and Statistical Manual of Mental Disorders-4th edition (DSM-IV). Appropriate scales were used for measuring the behavioral traits in probands. Genotyping was performed through PCR-based amplification of target sites followed by DNA-sequencing and/or gel-electrophoresis. Data obtained were analyzed by family based statistical methods. Results Out of 58 variants present in the analyzed sites only 15 were found to be polymorphic (30 bp-uVNTR, rs5906883, rs1465107, rs1465108, rs5905809, rs5906957, rs6323, rs1137070 from MAOA and rs4824562, rs56220155, rs2283728, rs2283727, rs3027441, rs6324, rs3027440 from MAOB). Statistically significant maternal transmission of alleles to male probands was observed for MAOA rs5905809 ‘G’ (p = 0.04), rs5906957 ‘A’ (p = 0.04), rs6323 ‘G’ (p = 0.0001) and MAOB rs56220155 ‘A’ (p = 0.002), rs2283728 ‘C’ (p = 0.0008), rs2283727 ‘C’ (p = 0.0008), rs3027441 ‘T’ (p = 0.003), rs6324 ‘C’ (p = 0.003), rs3027440 ‘T’ (p = 0.0002). Significantly preferential maternal transmissions of different haplotype combinations to male probands were also noticed (p < 0.05), while female probands did not reveal such transmission bias. Behavioral traits of male probands exhibited significant association with gene variants. Age of the mother at pregnancy also revealed association with risk variants of male probands. Conclusions It may be inferred that the MAOA and MAOB variants may contribute to the etiology of ADHD in the Indo-Caucasoid population and could be responsible for higher occurrence of ADHD in the boys

Additional file 3: of Monoamine oxidase B gene variants associated with attention deficit hyperactivity disorder in the Indo-Caucasoid population from West Bengal

Functional significance of MAOB polymorphic variants predicted in silico using is-rSNP. Description: The table summarizes functional regulatory role of MAOB polymorphic variants. (XLSX 40 kb

Genetic effect of monoamine oxidase B (MAOB) gene on ASD associated behavior phenotypes

Autism spectrum disorder (ASD) is a male predominance, behaviorally defined neurodevelopmental disorder which is characterized by impairment in social communication and restricted and repetitive activities. Abnormalities in serotoninergic function play a major role in ASD pathophysiology. Monoamine oxidases, encoded by two X-chromosomal genes MAOA and MAOB regulate the serotonergic function by the degradation of serotonin and other biological amines. Therefore, the objective of present study is to investigate genetic correlation of MAOB markers with the severity of specific behavioral traits as scored by Childhood Autism Rating Scale (CARS) has been examined as quantitative trait (QT) analysis using IBM-SPSS program. A total of 225 ASD patients (190 male and 35 female) were recruited after psychometric evaluation done by DSM-IV-TR/DSM-5 criteria and assessment by CARS. Genotyping carried by PCR/RFLP/sequencing methods, and population were found in Hardy-Weinberg equilibrium. The outcome of the QT analysis indicating the increased score in overall CARS were associated with G and C allele of MAOB marker rs3027449 (p-value: 0.03) and rs1040399 (p-value: 0.01), respectively in male ASD children. In addition to this, major alleles of studied polymorphisms of gene were found to be statistically associated with the higher impairment in social communication domain only in male ASD children. Overall outcome of the study suggests likely involvement of MAOB with ASD in a gender-specific manner with the severity in behavior phenotypes. Considering the cumulative impact of these markers in regulating the severity of the behavioral symptoms of ASD, it is likely that MAOB gene is associated with the disorder

CFD Analysis of a Pelton Turbine in OpenFOAM

During the spring of 2012, Lorentz Fjellanger Barstad developed a method for modelling the flow in a Pelton turbine subject to a high-speed water jet using the Computational Fluid Dynamics (CFD) software ANSYS CFX. The torque measurement was validated against experimental data. The aim of this master's thesis has been to develop a similar method with the Open Source tool OpenFOAM and to compare the two models.A method has been created using the OpenFOAM solver interDyMFoam, capable of handling two-phase flow together with mesh motion. The approach has been to use both a stationary and a rotating mesh domain to allow for the relative motion between the high-speed jet and the turbine buckets. The Arbitrary Mesh Interface (AMI) was used as a boundary condition for the patches between the two domains to allow simulation between them. Meshing was done both with the built-in tool snappyHexMesh and with ANSYS Meshing. The latter gave the best control over mesh refinement and the mesh quality.The results achieved from the method were unfortunately not as desired. Much water seems to accumulate between the buckets, giving severe backwash. The measured torque was significantly larger than both the experimental torque and the torque measured with the ANSYS CFX method. Additionally, the torque measurement curve from OpenFOAM contained instabilities and did not coincide well with the one generated in ANSYS CFX. The measured maximum torque of the method seemed to go towards the actual solution when the density of the mesh increased, but at the same time it gave more noise in the output, and made smoothing of the results necessary. The computational time needed for the simulations has been problematic, being almost thirty times that of ANSYS CFX

Study of time irrigation on grow, development and water comsuption in potted Dinathus caryophyllus L.

Un experimento de riego de clavel en maceta bajo invernadero-umbráculo fue diseñado para conocer la influencia de la hora de riego sobre el crecimiento, desarrollo y la eficiencia de la utilización del agua.Escuela Técnica superior de Ingeniería AgronómicaUniversidad Politécnica de Cartagen