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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
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
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 ( ) 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
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...
February 14, 2017: International Journal of Developmental Neuroscience
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
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
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
Vito S Hernández, Oscar R Hernández, Miguel Perez de la Mora, María J Gómora, Kjell Fuxe, Lee E Eiden, Limei Zhang
The arginine-vasopressin (AVP)-containing hypothalamic magnocellular neurosecretory neurons (VPMNNs) are known for their role in hydro-electrolytic balance control via their projections to the neurohypophysis. Recently, projections from these same neurons to hippocampus, habenula and other brain regions in which vasopressin infusion modulates contingent social and emotionally-affected behaviors, have been reported. Here, we present evidence that VPMNN collaterals also project to the amygdaloid complex, and establish synaptic connections with neurons in central amygdala (CeA)...
2016: Frontiers in Neural Circuits
Brooke C Jarvie, Connie M King, Alexander R Hughes, Matthew S Dicken, Christina S Dennison, Shane T Hentges
KEY POINTS: Hypothalamic proopiomelanocortin (POMC) neurons release peptide products that potently inhibit food intake and reduce body weight. These neurons also release the amino acid transmitter GABA, which can inhibit downstream neurons. Although the release of peptide transmitters from POMC neurons is regulated by energy state, whether similar regulation of GABA release might occur had not been examined. The present results show that the GABAergic phenotype of POMC neurons is decreased selectively by caloric deficit and not altered by high-fat diet or stress...
January 15, 2017: Journal of Physiology
Karen P Maruska, Julie M Butler, Karen E Field, Danielle T Porter
Neural communication depends on release and reception of different neurotransmitters within complex circuits that ultimately mediate basic biological functions. We mapped the distribution of glutamatergic, GABAergic, and cholinergic neurons in the brain of the African cichlid fish Astatotilapia burtoni using in situ hybridization to label vesicular glutamate transporters (vglut1, vglut2.1, vglut3), glutamate decarboxylases (gad1, gad2), and choline acetyltransferase (chat). Cells expressing the glutamatergic markers vgluts 1-3 show primarily nonoverlapping distribution patterns, with the most widespread expression observed for vglut2...
February 15, 2017: Journal of Comparative Neurology
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
David I Wasserman, Joel M J Tan, Jun Chul Kim, John S Yeomans
Opioids induce rewarding and locomotor effects by inhibiting rostromedial tegmental GABA neurons that express μ-opioid and nociceptin receptors. These GABA neurons then strongly inhibit dopamine neurons. Opioid-induced reward, locomotion and dopamine release also depend on pedunculopontine and laterodorsal tegmental cholinergic and glutamate neurons, many of which project to and activate ventral tegmental area dopamine neurons. Here we show that laterodorsal tegmental and pedunculopontine cholinergic neurons project to both rostromedial tegmental nucleus and ventral tegmental area, and that M4 muscarinic receptors are co-localized with μ-opioid receptors associated with rostromedial tegmental GABA neurons...
July 2016: European Journal of Neuroscience
Dereje Worku Mekonnen, Ulf-Ingo Flügge, Frank Ludewig
A rapid accumulation of γ-aminobutyric acid (GABA) during biotic and abiotic stresses is well documented. However, the specificity of the response and the primary role of GABA under such stress conditions are hardly understood. To address these questions, we investigated the response of the GABA-depleted gad1/2 mutant to drought stress. GABA is primarily synthesized from the decarboxylation of glutamate by glutamate decarboxylase (GAD) which exists in five copies in the genome of Arabidopsis thaliana. However, only GAD1 and GAD2 are abundantly expressed, and knockout of these two copies dramatically reduced the GABA content...
April 2016: Plant Science: An International Journal of Experimental Plant Biology
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
Xin Jin, Shanshan Li, Brian Bondy, Weiwei Zhong, Max F Oginsky, Yang Wu, Christopher M Johnson, Shuang Zhang, Ningren Cui, Chun Jiang
The locus coeruleus (LC)-norepinephrine (NE) system in the brainstem plays a critical role in a variety of behaviors is an important target of pharmacological intervention to several neurological disorders. Although GABA is the major inhibitory neurotransmitter of LC neurons, the modulation of LC neuronal firing activity by local GABAergic interneurons remains poorly understood with respect to their precise location, intrinsic membrane properties and synaptic modulation. Here, we took an optogenetic approach to address these questions...
2016: PloS One
Ruben A Tikidji-Hamburyan, Joan José Martínez, John A White, Carmen C Canavier
UNLABELLED: Gamma oscillations are believed to play a critical role in in information processing, encoding, and retrieval. Inhibitory interneuronal network gamma (ING) oscillations may arise from a coupled oscillator mechanism in which individual neurons oscillate or from a population oscillator in which individual neurons fire sparsely and stochastically. All ING mechanisms, including the one proposed herein, rely on alternating waves of inhibition and windows of opportunity for spiking...
November 25, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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
Xueyan Zhou, Qiuxiang Zhu, Xiaowen Han, Renguo Chen, Yaowu Liu, Hongbin Fan, Xiaoxing Yin
Diabetic encephalopathy (DE) is one of the most prevalent chronic complications of diabetes mellitus (DM), with neither effective prevention nor proven therapeutic regimen. This study aims to uncover the potential dysregulation pattern of the neurotransmitters in a rat model of streptozotocin (STZ)-induced experimental DE. For that purpose, male Sprague-Dawley (SD) rats were treated with a single intraperitoneal injection of STZ. Cognitive performance was detected with the Morris water maze (MWM) test. Serum, cerebrospinal fluid (CSF), and brain tissues were collected to measure the levels of neurotransmitters...
November 2015: Canadian Journal of Physiology and Pharmacology
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