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Gad2 gene

Brian P Grone, Karen P Maruska
Gamma-aminobutyric acid (GABA) is a widely conserved signaling molecule that in animals has been adapted as a neurotransmitter. GABA is synthesized from the amino acid glutamate by the action of glutamate decarboxylases (GADs). Two vertebrate genes, GAD1 and GAD2, encode distinct GAD proteins: GAD67 and GAD65, respectively. We have identified a third vertebrate GAD gene, GAD3. This gene is conserved in fishes as well as tetrapods. We analyzed protein sequence, gene structure, synteny, and phylogenetics to identify GAD3 as a homolog of GAD1 and GAD2...
2016: Scientific Reports
Jai Prakash, Balraj Mittal, Shally Awasthi, Neena Srivastava
BACKGROUND: Obesity associated with type 2 diabetes, and hypertension increased mortality and morbidity. Glutamate decarboxylase 2 (GAD2) gene is associated with obesity and it regulate food intake and insulin level. We investigated the association of GAD-2gene -243A>G (rs2236418) and +61450C>A (rs992990) polymorphisms with obesity and related phenotypes. METHODS: Insulin, glucose and lipid levels were estimated using standard protocols. All subjects were genotyped (PCR-RFLP) method...
April 2016: Iranian Journal of Public Health
Cynthia A Kelm-Nelson, Sharon A Stevenson, Michelle R Ciucci
Vocal communication deficits are common in Parkinson disease (PD). Widespread alpha-synuclein pathology is a common link between familial and sporadic PD, and recent genetic rat models based on familial genetic links increase the opportunity to explore vocalization deficits and their associated neuropathologies. Specifically, the Pink1 knockout (-/-) rat presents with early, progressive motor deficits, including significant vocal deficits, at 8 months of age. Moreover, this rat model exhibits alpha-synuclein pathology compared to age-matched non-affected wildtype (WT) controls...
May 16, 2016: Neuroscience Letters
Kasey N Davis, Ran Tao, Chao Li, Yuan Gao, Marjorie C Gondré-Lewis, Barbara K Lipska, Joo Heon Shin, Bin Xie, Tianzhang Ye, Daniel R Weinberger, Joel E Kleinman, Thomas M Hyde
Genetic variation and early adverse environmental events work together to increase risk for schizophrenia. γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in adult mammalian brain, plays a major role in normal brain development, and has been strongly implicated in the pathobiology of schizophrenia. GABA synthesis is controlled by two glutamic acid decarboxylase (GAD) genes, GAD1 and GAD2, both of which produce a number of alternative transcripts. Genetic variants in the GAD1 gene are associated with increased risk for schizophrenia, and reduced expression of its major transcript in the human dorsolateral prefrontal cortex (DLPFC)...
2016: PloS One
Peter H Frederikse, Chinnaswamy Kasinathan
PURPOSE: Na-K-Cl cotransporter 1 (NKCC1) and K-Cl cotransporter 2 (KCC2) have fundamental roles in neuron differentiation that are integrated with gamma-aminobutyric acid (GABA) and glutamate receptors, GABA synthesized by GAD25/65/67 encoded by GAD1/GAD2 genes, and GABA transporters (GATs). Cells in the eye lens express at least 13 GABA receptor subunits, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl D-aspartate (NMDA) glutamate receptors, GAD1/GAD2, GAT1-4 and vGAT, and NKCC1...
2015: Molecular Vision
Mikhail Umorin, Crystal Stinson, Larry L Bellinger, Phillip R Kramer
Pain can vary over the estrous cycle as a result of changes in estradiol concentration but the mechanism causing this variation is unclear. Because the thalamus is important in pain control, gene expression in the lateral thalamus (ventral posteromedial, ventral posterolateral, reticular thalamic nuclei) was screened at different phases of the estrous cycle. Gene expression changes in Sprague-Dawley rats were further analyzed by real-time PCR and ELISA and plasma estradiol levels were measured by RIAs at different phases of the estrous cycle...
May 2016: Journal of Cellular Physiology
Stefanie Besser, Marit Sicker, Grit Marx, Ulrike Winkler, Volker Eulenburg, Swen Hülsmann, Johannes Hirrlinger
GABAergic inhibitory neurons are a large population of neurons in the central nervous system (CNS) of mammals and crucially contribute to the function of the circuitry of the brain. To identify specific cell types and investigate their functions labelling of cell populations by transgenic expression of fluorescent proteins is a powerful approach. While a number of mouse lines expressing the green fluorescent protein (GFP) in different subpopulations of GABAergic cells are available, GFP expressing mouse lines are not suitable for either crossbreeding to other mouse lines expressing GFP in other cell types or for Ca2+-imaging using the superior green Ca2+-indicator dyes...
2015: PloS One
Jennifer Ngolab, Liwang Liu, Rubing Zhao-Shea, Guangping Gao, Paul D Gardner, Andrew R Tapper
Chronic nicotine exposure increases sensitivity to nicotine reward during a withdrawal period, which may facilitate relapse in abstinent smokers, yet the molecular neuroadaptation(s) that contribute to this phenomenon are unknown. Interestingly, chronic nicotine use induces functional upregulation of nicotinic acetylcholine receptors (nAChRs) in the mesocorticolimbic reward pathway potentially linking upregulation to increased drug sensitivity. In the ventral tegmental area (VTA), functional upregulation of nAChRs containing the α4 subunit (α4* nAChRs) is restricted to GABAergic neurons...
June 3, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Q Li, Z R Qiao, D B Liu, J T Zeng, J Zhang, Y Bo, H Y Zu, Q Hu, X Wu, S S Dong
In this study, we investigated the relationship between serum glutamic acid decarboxylase (GAD) autoantibody (Ab) levels and single nucleotide polymorphisms (SNPs) of the glutamic acid de-carboxylase 2 (GAD2) 5'-untranslated region and the susceptibility to type 2 diabetes in the Han population. The distributions of patients with SNPs in the GAD2 5'-untranslated region (rs2236418, rs185649317, and rs8190590) and type 2 diabetes and that of the healthy group were genotyped and analyzed using Sequenom MassArray SNP genotyp-ing...
2015: Genetics and Molecular Research: GMR
K Meganathan, S Jagtap, S P Srinivasan, V Wagh, J Hescheler, J Hengstler, M Leist, A Sachinidis
Human embryonic stem cells (hESCs) may be applied to develop human-relevant sensitive in vitro test systems for monitoring developmental toxicants. The aim of this study was to identify potential developmental toxicity mechanisms of the histone deacetylase inhibitors (HDAC) valproic acid (VPA), suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA) relevant to the in vivo condition using a hESC model in combination with specific differentiation protocols and genome-wide gene expression and microRNA profiling...
2015: Cell Death & Disease
Wenjuan Tao, Quan Chen, Lu Wang, Wenjie Zhou, Yunping Wang, Zhi Zhang
Our previous study demonstrated that persistent pain can epigenetically suppress the transcription of Gad2 [encoding glutamic acid decarboxylase 65 (GAD65)] and consequently impair the inhibitory function of GABAergic synapses in central pain-modulating neurons. This contributes to the development of persistent pain sensitization. Histone deacetylase (HDAC) inhibitors increased GAD65 activity considerably, restored GABA synaptic function, and rendered sensitized pain behavior less pronounced. However, the molecular mechanisms by which HDAC regulates GABAergic transmission through GAD65 under pain conditions are unknown...
June 2015: Molecular Pharmacology
I P Makariti, A Printezi, A E Kapetanakou, N Zeaki, P N Skandamis
The objective of this study was to correlate the relative transcription of Listeria monocytogenes (strains C5, 6179) stress- (gad2, sigB) and virulence- (prfA) associated genes following habituation at twenty-five pH (4.8, 5.0, 5.2, 5.5, 6.4) and NaCl (2, 4, 6, 8, 10% w/v) combinations at 7 °C, with the survival against subsequent exposure to severe acid stress (pH 2.0 at 37 °C). Our findings pointed out the inter-strain variation governing growth inhibiting conditions (pH ≤5.0 and NaCl ≥6%), where C5 was less affected (a reduction of 2...
February 2015: Food Microbiology
Viola Tamási, Peter Petschner, Csaba Adori, Eszter Kirilly, Romeo D Ando, Laszlo Tothfalusi, Gabriella Juhasz, Gyorgy Bagdy
OBJECTIVES: Venlafaxine (VLX), a serotonine-noradrenaline reuptake inhibitor, is one of the most commonly used antidepressant drugs in clinical practice for the treatment of major depressive disorder (MDD). Despite being more potent than its predecessors, similarly to them, the therapeutical effect of VLX is visible only 3-4 weeks after the beginning of treatment. Furthermore, recent papers show that antidepressants, including also VLX, enhance the motor recovery after stroke even in non depressed persons...
2014: PloS One
Debasish Roy, Gloria M Calaf
Identification of markers with the potential to predict tumorigenic behavior is important in breast cancer, due to the variability in clinical disease progression. Genetic alterations during neoplastic progression may appear as changes in total DNA content, single genes, or gene expression. Oncogenic alterations are thought to be prognostic indices for patients with breast cancer. Breast cancer deregulation can occur in the normal cellular process and can be measured by microsatellite instability (MSI)/loss of heterozygosity (LOH)...
December 2014: Oncology Reports
Stefan Trifonov, Yuji Yamashita, Masahiko Kase, Masato Maruyama, Tetsuo Sugimoto
BACKGROUND: GABA has important functions in brain plasticity related processes like memory, learning, locomotion and during the development of the nervous system. It is synthesized by the glutamic acid decarboxylase (GAD). There are two isoforms of GAD, GAD1 and GAD2, which are encoded by different genes. During embryonic development the transcription of GAD1 mRNA is regulated by alternative splicing and several alternative transcripts were distinguished in human, mouse and rat. Despite the fact that the structure of GAD1 gene has been extensively studied, knowledge of its exact structural organization, alternative promoter usage and splicing have remained incomplete...
2014: BMC Neuroscience
Chia Lin Chang, James J Cai, Shang Yu Huang, Po Jen Cheng, Ho Yen Chueh, Sheau Yu Teddy Hsu
Recent analyses have identified positively selected loci that explain differences in immune responses, body forms, and adaptations to extreme climates, but variants that describe adaptations in energy-balance regulation remain underexplored. To identify variants that confer adaptations in energy-balance regulation, we explored the evolutionary history and functional associations of candidate variants in 207 genes. We screened single nucleotide polymorphisms in genes that had been associated with energy-balance regulation for unusual genetic patterns in human populations, followed by studying associations among selected variants and serum levels of GIP, insulin, and C-peptide in pregnant women after an oral glucose tolerance test...
2014: PloS One
Sally França Lacerda-Pinheiro, Roberto Flávio Fontenelle Pinheiro Junior, Marcos Antonio Pereira de Lima, Claúdio Gleidiston Lima da Silva, Maria do Socorro Vieira dos Santos, Antonio Gilvan Teixeira Júnior, Pedro Neto Lima de Oliveira, Karla Denise Barros Ribeiro, Modesto Leite Rolim-Neto, Bianca Alves Vieira Bianco
BACKGROUND: Genetic factors may encourage or even cause the occurrence of mood disorders such as anxiety and/or depression. However, despite the significant amount of work and sophisticated technology is not fully elucidated which genes or regions of nuclear or mitochondrial DNA, or which types of genetic changes, alone or in combination, can represent reliable genetic markers of anxiety and/or depression. OBJECTIVE: To identify whether there are genetic changes that can cause depression or anxiety and if there are genetic markers that can be used to detect these changes...
October 2014: Journal of Affective Disorders
Marcos Leite Santoro, Camila Maurício Santos, Vanessa Kiyomi Ota, Ary Gadelha, Roberta Sessa Stilhano, Mariana Cepollaro Diana, Patrícia Natália Silva, Letícia Maria Nery Spíndola, Maria Isabel Melaragno, Rodrigo Affonseca Bressan, Sang Won Han, Vanessa Costhek Abílio, Sintia Iole Belangero
The spontaneously hypertensive rat (SHR) strain was shown to be a useful animal model to study several behavioral, pathophysiological and pharmacological aspects of schizophrenia and attention-deficit/hyperactivity disorder. To further understand the genetic underpinnings of this model, our primary goal in this study was to compare the gene expression profile of neurotransmitter receptors and regulators in the prefrontal cortex (PFC) and nucleus accumbens (NAcc) of SHR and Wistar rats (control group). In addition, we investigated DNA methylation pattern of promoter region of the genes differentially expressed...
November 30, 2014: Psychiatry Research
S Mas, M Pagerols, P Gassó, A Ortiz, N Rodriguez, A Morer, M T Plana, A Lafuente, L Lazaro
One of the leading biological models of obsessive-compulsive disorder (OCD) is the frontal-striatal-thalamic model. This study undertakes an extensive exploration of the variability in genes related to the regulation of the frontal-striatal-thalamic system in a sample of early-onset OCD trios. To this end, we genotyped 266 single nucleotide polymorphisms (SNPs) in 35 genes in 84 OCD probands and their parents. Finally, 75 complete trios were included in the analysis. Twenty SNPs were overtransmitted from parents to early-onset OCD probands and presented nominal pointwise P < 0...
April 2014: Genes, Brain, and Behavior
A Zhubi, Y Chen, E Dong, E H Cook, A Guidotti, D R Grayson
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by symptoms related to altered social interactions/communication and restricted and repetitive behaviors. In addition to genetic risk, epigenetic mechanisms (which include DNA methylation/demethylation) are thought to be important in the etiopathogenesis of ASD. We studied epigenetic mechanisms underlying the transcriptional regulation of candidate genes in cerebella of ASD patients, including the binding of MeCP2 (methyl CpG binding protein-2) to the glutamic acid decarboxylase 67 (GAD1), glutamic acid decarboxylase 65 (GAD2), and Reelin (RELN) promoters and gene bodies...
2014: Translational Psychiatry
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