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001-es BibID:	BIBFORM019004
Első szerző:	Gyetvai Beatrix
Cím:	mGluR7 genetics and alcohol : intersection yields clues for addiction / Beatrix Gyetvai, Agnes Simonyi, Melinda Oros, Mariko Saito, John Smiley, Csaba Vadász
Dátum:	2011
ISSN:	0364-3190
Megjegyzések:	Development of addiction to alcohol or other substances can be attributed in part to exposure-dependent modifications at synaptic efficacy leading to an organism which functions at an altered homeostatic setpoint. Genetic factors may also influence setpoints and the stability of the homeostatic system of an organism. Quantitative genetic analysis of voluntary alcohol drinking, and mapping of the involved genes in the quasi-congenic Recombinant QTL Introgression strain system, identified Eac2 as a Quantitative Trait Locus (QTL) on mouse chromosome 6 which explained 18% of the variance with an effect size of 2.09 g/kg/day alcohol consumption, and Grm7 as a quantitative trait gene underlying Eac2 [Vadasz et al. in Neurochem Res 32:1099-1112, 100, Genomics 90:690-702, 102]. In earlier studies, the product of Grm7 mGluR7, a G protein-coupled receptor, has been implicated in stress systems [Mitsukawa et al. in Proc Natl Acad Sci USA 102:18712-18717, 63], anxiety-like behaviors [Cryan et al. in Eur J Neurosci 17:2409-2417, 14], memory [Holscher et al. in Learn Mem 12:450-455, 26], and psychiatric disorders (e.g., [Mick et al. in Am J Med Genet B Neuropsychiatr Genet 147B:1412-1418, 61; Ohtsuki et al. in Schizophr Res 101:9-16, 72; Pergadia et al. in Paper presented at the 38th Annual Meeting of the Behavior Genetics Association, Louisville, Kentucky, USA, 76]. Here, in experiments with mice, we show that (1) Grm7 knockout mice express increased alcohol consumption, (2) sub-congenic, and congenic mice carrying a Grm7 variant characterized by higher Grm7 mRNA drink less alcohol, and show a tendency for higher circadian dark phase motor activity in a wheel running paradigm, respectively, and (3) there are significant genetic differences in Grm7 mRNA abundance in the mouse brain between congenic and background mice identifying brain areas whose function is implicated in addiction related processes. We hypothesize that metabotropic glutamate receptors may function as regulators of homeostasis, and Grm7 (mGluR7) is involved in multiple processes (including stress, circadian activity, reward control, memory, etc.) which interact with substance use and the development of addiction. In conclusion, we suggest that mGluR7 is a significant new therapeutic target in addiction and related neurobehavioral disorders.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	Neurochemical Research. - 36 : 6 (2011), p. 1087-1100. -
További szerzők:	Simonyi Ágnes (biokémikus) Oros Melinda (1975-) (molekuláris biológus) Saito, Mariko Smiley, John Vadász Csaba
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001-es BibID:	BIBFORM047535
Első szerző:	Vadász Csaba
Cím:	Glutamate receptor metabotropic 7 is cis-regulated in the mouse brain and modulates alcohol drinking? / Csaba Vadasz, Mariko Saito, Beatrix M. Gyetvai, Melinda Oros, Istvan Szakall, Krisztina M. Kovacs, Vidudala V. T. S. Prasad, Reka Toth
Dátum:	2007
ISSN:	0888-7543
Megjegyzések:	Alcoholism is a heritable disease that afflicts about 8% of the adult population. Its development and symptoms, such as craving, loss of control, physical dependence, and tolerance, have been linked to changes in mesolimbic, mesocortical neurotransmitter systems utilizing biogenic amines, GABA, and glutamate. Identification of genes predisposing to alcoholism, or to alcohol-related behaviors in animal models, has been elusive because of variable interactions of multiple genes with relatively small individual effect size and sensitivity of the predisposing genotype to lifestyle and environmental factors. Here, using near-isogenic advanced animal models with reduced genetic background interactions, we integrate gene mapping and gene mRNA expression data in segregating and congenic mice and identify glutamate receptor metabotropic 7 (Grm7) as a cis-regulated gene for alcohol consumption. Traditionally, the mesoaccumbal dopamine reward hypothesis of addiction and the role of the ionotropic glutamate receptors have been emphasized. Our results lend support to an emerging direction of research on the role of metabotropic glutamate receptors in alcoholism and drug addiction. These data suggest for the first time that Grm7 is a risk factor for alcohol drinking and a new target in addiction therapy.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	Genomics. - 90 : 6 (2007), p. 690-702. -
További szerzők:	Saito, Mariko Gyetvai Beatrix Oros Melinda (1975-) (molekuláris biológus) Szakáll István Kovács Krisztina M. Prasad, Vidudala V. T. S. Tóth Réka
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001-es BibID:	BIBFORM039786
Első szerző:	Vadász Csaba
Cím:	Mesencephalic dopamine neuron number and tyrosine hydroxylase content: Genetic control and candidate genes / Vadasz, C., Smiley, J. F., Figarsky, K., Saito, M., Toth, R., Gyetvai, B. M., Oros, M., Kovacs, K. K., Mohan, P., Wang, R.
Dátum:	2007
ISSN:	0306-4522
Megjegyzések:	The mesotelencephalic dopamine system shows substantial genetic variation which fundamentally affects normal and pathological behaviors related to motor function, motivation, and learning. Our earlier radioenzyme assay studies demonstrated significantly higher activity of tyrosine hydroxylase (TH), the first and rate limiting enzyme in the biosynthesis of catecholamine neurotransmitters, in the substantia nigra-ventral tegmental area of BALB/cJ mice in comparison with that of C57BL/6ByJ mice. Here, using quantitative immunoblotting and immunocytochemistry, we tested the hypothesis that mesencephalic TH protein content and number of nigral TH-positive neurons show strain-dependent differences in C57BL/6ByJ and BALB/cJ parallel to those observed in the TH activity studies. Immunoblotting experiments detected significantly higher mesencephalic TH protein content in BALB/cJ in comparison to C57BL/6ByJ (P<0.05). Immunocytochemical studies demonstrated that the number of TH-positive cells in substantia nigra was 31.3% higher in BALB/cJ than that in C57BL/6ByJ (P<0.01), while the average dopamine neuron volume was not significantly different. In a search for candidate genes that modulate TH content and the size of mesencephalic dopamine neuron populations we also studied near-isogenic mouse sublines derived from the C57BL/6ByJ and BALB/cJ progenitor strains. A whole-genome scan with 768 single nucleotide polymorphism markers indicated that two sublines, C4A6/N and C4A6/B, were genetically very similar (98.3%). We found significantly higher mesencephalic TH protein content in C4A6/B in comparison to C4A6/N (P=0.01), and a tendency for higher number of dopamine neurons in the substantia nigra in C4A6/B in comparison to C4A6/N, which, however, did not reach statistical significance. To identify the genetic source of the TH content difference we analyzed the single nucleotide polymorphism (SNP) genotype data of the whole-genome scan, and detected two small differential chromosome segments on chr. 13 and chr. 14. Microarray gene expression studies and bioinformatic analysis of the two differential regions implicated two cis-regulated genes (Spock1 and Cxcl14, chr. 13), and two growth factor genes [bone morphogenetic protein 6 (Bmp6) (chr. 13), and fibroblast growth factor 14 (Fgf14) (chr. 14)]. Taken together, the results suggest that (1) nigral dopamine neuron number and TH protein content may be genetically associated but further studies are needed to establish unequivocally this linkage, and (2) Spock1, Cxcl14, Bmp6, and Fgf14 are novel candidates for modulating the expression and maintenance of TH content in mesencephalic dopamine neurons in vivo.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	Neuroscience. - 149 : 3 (2007), p. 561-572. -
További szerzők:	Smiley, John Figarsky, K. Saito, Mariko Tóth Réka Gyetvai Beatrix Oros Melinda (1975-) (molekuláris biológus) Kovács, K. K. Mohan, Puneet Wang, Rui
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001-es BibID:	BIBFORM039712
035-os BibID:	PMID:17273929
Első szerző:	Vadász Csaba
Cím:	Mapping of QTLs for oral alcohol self-administration in B6.C and B6.I quasi-congenic RQI strains / Csaba Vadasz, Mariko Saito, Beatrix Gyetvai, Melinda Oros, Istvan Szakall, Krisztina M. Kovacs, Vidudala V. T. S. Prasad, Grant Morahan, Reka Toth
Dátum:	2007
ISSN:	0364-3190
Megjegyzések:	One strategy to identify neurochemical pathways of addiction is to map the relevant genes. In the present study we used 43 B6.C and 35 B6.I inbred RQI mouse strains, carrying <3% donor genome on C57BL/6ByJ background, for gene mapping. The strains were phenotyped for consumption of alcohol (12% v/v) in a two-bottle-choice paradigm, and genotyped for 396 microsatellite markers. The current mapping study extends our earlier experiment scanning five mouse chromosomes (Vadasz et al. (2000) Scanning of five chromosomes for alcohol consumption loci. Alcohol 22:25-34) to a whole-genome study, and discusses the differences and limitations. Data were analyzed with composite interval (CIM) and multiple interval (MIM) QTL mapping methods. CIM of B6.C strains detected significant QTLs on chrs. 6 and 12. A suggestive, but not significant, locus was detected in the B6.I strains on chr. 12. The best MIM model for B6.C strains confirmed one QTL on chr. 6 and one QTL on chr. 12, while the MIM model for the B6.I strains confirmed the suggestive locus on chr. 12. Some of the QTLs for alcohol consumption are new, while others confirm previously reported QTLs for alcohol preference, and alcohol acceptance.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban külföldön készült közlemény
Megjelenés:	Neurochemical Research. - 32 : 7 (2007), p. 1099-1112. -
További szerzők:	Saito, Mariko Gyetvai Beatrix Oros Melinda (1975-) (molekuláris biológus) Szakáll István Kovács Krisztina M. Prasad, Vidudala V. T. S. Morahan, Grant Tóth Réka
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