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https://www.readbyqxmd.com/read/29028947/dlx1-and-dlx2-promote-interneuron-gaba-synthesis-synaptogenesis-and-dendritogenesis
#1
Ramon Pla, Amelia Stanco, MacKenzie A Howard, Anna N Rubin, Daniel Vogt, Niall Mortimer, Inma Cobos, Gregory Brian Potter, Susan Lindtner, James D Price, Alex S Nord, Axel Visel, Christoph E Schreiner, Scott C Baraban, David H Rowitch, John L R Rubenstein
The postnatal functions of the Dlx1&2 transcription factors in cortical interneurons (CINs) are unknown. Here, using conditional Dlx1, Dlx2, and Dlx1&2 knockouts (CKOs), we defined their roles in specific CINs. The CKOs had dendritic, synaptic, and survival defects, affecting even PV+ CINs. We provide evidence that DLX2 directly drives Gad1, Gad2, and Vgat expression, and show that mutants had reduced mIPSC amplitude. In addition, the mutants formed fewer GABAergic synapses on excitatory neurons and had reduced mIPSC frequency...
September 28, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28821666/gabaergic-interneuron-differentiation-in-the-basal-forebrain-is-mediated-through-direct-regulation-of-glutamic-acid-decarboxylase-isoforms-by-dlx-homeobox-transcription-factors
#2
Trung N Le, Qing-Ping Zhou, Inma Cobos, Shunzhen Zhang, Jamie Zagozewski, Sara Japoni, Jerry Vriend, Tracie Parkinson, Guoyan Du, John L Rubenstein, David D Eisenstat
GABA is the key inhibitory neurotransmitter in the cortex but regulation of its synthesis during forebrain development is poorly understood. In the telencephalon, members of the distal-less (Dlx) homeobox gene family are expressed in, and regulate the development of, the basal ganglia primodia from which many GABAergic neurons originate and migrate to other forebrain regions. The Dlx1/Dlx2 double knock-out mice die at birth with abnormal cortical development, including loss of tangential migration of GABAergic inhibitory interneurons to the neocortex (Anderson et al...
September 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28751139/identification-of-driver-genes-and-key-pathways-of-pediatric-brain-tumor-and-comparison-of-molecular-pathogenesis-based-on-pathological-types
#3
Sheng Zhong, Bo Wu, Yujuan Han, Yingshu Cao, Liu Yang, Sean X Luo, Yong Chen, Huimao Zhang, Gang Zhao
OBJECTIVE: This study is to identify pediatric brain tumors (PBT) diver genes, key pathways, to detect the expression of the diver genes and also to clarify the relationship between patients' prognosis and diver genes expression. METHODS: The gene expression profile of GSE50161 was analyzed to identify the DEGs (Differentially Expressed Genes) between tumor tissue and the normal tissue. GO (Gene Ontology), KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis and PPI (Protein-protein interation) network analysis were conducted to find out the enrichment functions, pathways and hub genes...
July 24, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28743044/electrophysiological-and-gene-expression-characterization-of-the-ontogeny-of-nestin-expressing-cells-in-the-adult-mouse-midbrain
#4
Anupama Dey, Parisa Farzanehfar, Elena V Gazina, Tim D Aumann
The birth of new neurons, or neurogenesis, in the adult midbrain is important for progressing dopamine cell-replacement therapies for Parkinson's disease. Most studies suggest newborn cells remain undifferentiated or differentiate into glia within the adult midbrain. However, some studies suggest nestin+neural precursor cells (NPCs) have a propensity to generate new neurons here. We sought to confirm this by administering tamoxifen to adult NesCreER(T2)/R26eYFP transgenic mice, which permanently labelled adult nestin-expressing cells and their progeny with enhanced yellow fluorescent protein (eYFP)...
August 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28485403/gad1-alternative-transcripts-and-dna-methylation-in-human-prefrontal-cortex-and-hippocampus-in-brain-development-schizophrenia
#5
R Tao, K N Davis, C Li, J H Shin, Y Gao, A E Jaffe, M C Gondré-Lewis, D R Weinberger, J E Kleinman, T M Hyde
Genetic variations and adverse environmental events in utero or shortly after birth can lead to abnormal brain development and increased risk of schizophrenia. γ-Aminobutyric acid (GABA), the major inhibitory neurotransmitter in the mammalian brain, plays a vital role in normal brain development. GABA synthesis is controlled by enzymes derived from two glutamic acid decarboxylase (GAD) genes, GAD1 and GAD2, both of which produce transcript isoforms. While the full-length GAD1 transcript (GAD67) has been implicated in the neuropathology of schizophrenia, the transcript structure of GAD1 in the human brain has not been fully characterized...
May 9, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28363755/an-investigation-of-gene-expression-in-single-cells-derived-from-nestin-expressing-cells-in-the-adult-mouse-midbrain-in-vivo
#6
Parisa Farzanehfar, Malcolm K Horne, Tim D Aumann
Generation of new dopamine (DA) neurons in the adult midbrain is a controversial issue in development of better treatments for Parkinson's disease (PD). Previous research suggests Nestin-expressing neural precursor cells (NPCs) have a propensity to differentiate into neurons here, including DA neurons. In the present study we sought confirmation of this by studying gene expression in single Nestin-expressing cells and their progeny/ontogeny within the adult mouse midbrain. Cells were identified by administering a pulse of Tamoxifen to adult Nestin-CreER(T2)×R26eYFP transgenic mice...
March 29, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28245795/in-search-of-druggable-targets-for-gbm-amino-acid-metabolism
#7
Eduard H Panosyan, Henry J Lin, Jan Koster, Joseph L Lasky
BACKGROUND: Amino acid (AA) pathways may contain druggable targets for glioblastoma (GBM). Literature reviews and GBM database ( http://r2.amc.nl ) analyses were carried out to screen for such targets among 95 AA related enzymes. METHODS: First, we identified the genes that were differentially expressed in GBMs (3 datasets) compared to non-GBM brain tissues (5 datasets), or were associated with survival differences. Further, protein expression for these enzymes was also analyzed in high grade gliomas (HGGs) (proteinatlas...
February 28, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28229923/epigenetic-regulation-of-reln-and-gad1-in-the-frontal-cortex-fc-of-autism-spectrum-disorder-asd-subjects
#8
Adrian Zhubi, Ying Chen, Alessandro Guidotti, Dennis R Grayson
Both Reelin (RELN) and glutamate decarboxylase 67 (GAD1) have been implicated in the pathophysiology of Autism Spectrum Disorders (ASD). We have previously shown that both mRNAs are reduced in the cerebella (CB) of ASD subjects through a mechanism that involves increases in the amounts of MECP2 binding to the corresponding promoters. In the current study, we examined the expression of RELN, GAD1, GAD2, and several other mRNAs implicated in this disorder in the frontal cortices (FC) of ASD and CON subjects. We also focused on the role that epigenetic processes play in the regulation of these genes in ASD brain...
November 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28122016/gad1-gene-expression-in-blood-of-patients-with-first-episode-psychosis
#9
Jie Yin Yee, Milawaty Nurjono, Stephanie Ruth Teo, Tih-Shih Lee, Jimmy Lee
γ-Aminobutyric acid (GABA), the primary inhibitory neurotransmitter, has often been studied in relation to its role in the pathophysiology of schizophrenia. GABA is synthesized from glutamate by glutamic acid decarboxylase (GAD), derived from two genes, GAD1 and GAD2. GAD1 is expressed as both GAD67 and GAD25 mRNA transcripts with the former reported to have a lower expression level in schizophrenia compared to healthy controls and latter was reported to be predominantly expressed fetally, suggesting a role in developmental process...
2017: PloS One
https://www.readbyqxmd.com/read/27983964/functional-consequences-of-i56ii-dlx-enhancer-deletion-in-the-developing-mouse-forebrain
#10
S Fazel Darbandi, L Poitras, S Monis, S Lindtner, M Yu, G Hatch, J L Rubenstein, M Ekker
Dlx homeobox genes encode a group of transcription factors that play an essential role during developmental processes including maintaining the differentiation, proliferation and migration of GABAergic interneurons. The Dlx1/2 and Dlx5/6 genes are expressed in the forebrain and are arranged in convergently transcribed bigene clusters, with I12a/I12b and I56i/I56ii cis-regulatory elements (CREs) located in the intergenic region of each cluster respectively. We have characterized the phenotypic consequences of deleting I56ii on forebrain development and spatial patterning of corridor cells that are involved in guiding thalamocortical projections...
October 27, 2016: Developmental Biology
https://www.readbyqxmd.com/read/27967329/association-of-polymorphisms-in-gad1-and-gad2-genes-with-methamphetamine-dependence
#11
Siriluk Veerasakul, Paritat Watiktinkorn, Samur Thanoi, Gavin P Reynolds, Sutisa Nudmamud-Thanoi
AIM: Association between polymorphisms in GAD genes and methamphetamine (METH) dependence was investigated in the Thai population. MATERIALS & METHODS: Genotypes of rs769404 and rs701492 in GAD1 and rs2236418 in GAD2 polymorphisms were determined in 100 METH-dependent male subjects and 102 matched controls. RESULTS: The genotype and allele frequencies of rs2236418 (GAD2) were associated with METH dependence and METH with psychosis, in which the G allele was related to increased risk...
January 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/27461130/three-distinct-glutamate-decarboxylase-genes-in-vertebrates
#12
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
https://www.readbyqxmd.com/read/27252915/association-of-the-243a-g-61450c-a-polymorphisms-of-the-glutamate-decarboxylase-2-gad2-gene-with-obesity-and-insulin-level-in-north-indian-population
#13
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
https://www.readbyqxmd.com/read/27057733/atp13a2-expression-in-the-periaqueductal-gray-is-decreased-in-the-pink1-rat-model-of-parkinson-disease
#14
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
https://www.readbyqxmd.com/read/26848839/gad2-alternative-transcripts-in-the-human-prefrontal-cortex-and-in-schizophrenia-and-affective-disorders
#15
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
https://www.readbyqxmd.com/read/26539026/kcc2-expression-supersedes-nkcc1-in-mature-fiber-cells-in-mouse-and-rabbit-lenses
#16
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
https://www.readbyqxmd.com/read/26388520/genes-in-the-gaba-pathway-increase-in-the-lateral-thalamus-of-sprague-dawley-rats-during-the-proestrus-estrus-phase
#17
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
https://www.readbyqxmd.com/read/26076353/a-transgenic-mouse-line-expressing-the-red-fluorescent-protein-tdtomato-in-gabaergic-neurons
#18
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
https://www.readbyqxmd.com/read/26041923/functional-upregulation-of-%C3%AE-4-nicotinic-acetylcholine-receptors-in-vta-gabaergic-neurons-increases-sensitivity-to-nicotine-reward
#19
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
https://www.readbyqxmd.com/read/25966064/relationship-between-serum-gad-ab-and-the-genetic-polymorphisms-of-gad2-and-type-2-diabetes-mellitus
#20
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
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