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cacna1c hippocampus

Charlotte C Bavley, Delaney K Fischer, Bryant K Rizzo, Anjali M Rajadhyaksha
Chronic stress is known to precipitate and exacerbate neuropsychiatric symptoms, and exposure to stress is particularly pathological in individuals with certain genetic predispositions. Recent genome wide association studies have identified single nucleotide polymorphisms (SNPs) in the gene CACNA1C , which codes for the Cav 1.2 subunit of the L-type calcium channel (LTCC), as a common risk variant for multiple neuropsychiatric conditions. Cav 1.2 channels mediate experience-dependent changes in gene expression and long-term synaptic plasticity through activation of downstream calcium signaling pathways...
December 2017: Neurobiology of Stress
Stephanie J Temme, Ryan Z Bell, Grace L Fisher, Geoffrey G Murphy
L-type voltage-gated calcium channels (LVGCCs) have been implicated in various forms of learning, memory, and synaptic plasticity. Within the hippocampus, the LVGCC subtype, CaV 1.2 is prominently expressed throughout the dentate gyrus. Despite the apparent high levels of CaV 1.2 expression in the dentate gyrus, the role of CaV 1.2 in hippocampal- and dentate gyrus-associated forms of learning remain unknown. To address this question, we examined alternate forms of hippocampal-dependent associative and spatial memory in mice lacking the mouse ortholog of CACNA1C ( Cacna1c ), which encodes CaV 1...
November 2016: ENeuro
Stefanie Uhrig, David Vandael, Andrea Marcantoni, Nina Dedic, Ainhoa Bilbao, Miriam A Vogt, Natalie Hirth, Laura Broccoli, Rick E Bernardi, Kai Schönig, Peter Gass, Dusan Bartsch, Rainer Spanagel, Jan M Deussing, Wolfgang H Sommer, Emilio Carbone, Anita C Hansson
It has previously been shown that the inhibition of L-type calcium channels (LTCCs) decreases alcohol consumption, although the contribution of the central LTCC subtypes Cav1.2 and Cav1.3 remains unknown. Here, we determined changes in Cav1.2 (Cacna1c) and Cav1.3 (Cacna1d) mRNA and protein expression in alcohol-dependent rats during protracted abstinence and naive controls using in situ hybridization and western blot analysis. Functional validation was obtained by electrophysiological recordings of calcium currents in dissociated hippocampal pyramidal neurons...
April 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
B H Schott, A Assmann, P Schmierer, J Soch, S Erk, M Garbusow, S Mohnke, L Pöhland, N Romanczuk-Seiferth, A Barman, T Wüstenberg, L Haddad, O Grimm, S Witt, S Richter, M Klein, H Schütze, T W Mühleisen, S Cichon, M Rietschel, M M Noethen, H Tost, E D Gundelfinger, E Düzel, A Heinz, A Meyer-Lindenberg, C I Seidenbecher, H Walter
Recent genome-wide association studies have pointed to single-nucleotide polymorphisms (SNPs) in genes encoding the neuronal calcium channel CaV1.2 (CACNA1C; rs1006737) and the presynaptic active zone protein Piccolo (PCLO; rs2522833) as risk factors for affective disorders, particularly major depression. Previous neuroimaging studies of depression-related endophenotypes have highlighted the role of the subgenual cingulate cortex (CG25) in negative mood and depressive psychopathology. Here, we aimed to assess how recently associated PCLO and CACNA1C depression risk alleles jointly affect memory-related CG25 activity as an intermediate phenotype in clinically healthy humans...
March 18, 2014: Translational Psychiatry
Susanne Erk, Andreas Meyer-Lindenberg, Phöbe Schmierer, Sebastian Mohnke, Oliver Grimm, Maria Garbusow, Leila Haddad, Lydia Poehland, Thomas W Mühleisen, Stephanie H Witt, Heike Tost, Peter Kirsch, Nina Romanczuk-Seiferth, Björn H Schott, Sven Cichon, Markus M Nöthen, Marcella Rietschel, Andreas Heinz, Henrik Walter
BACKGROUND: Variation in CACNA1C has consistently been associated with psychiatric disease in genome-wide association studies. We have previously shown that healthy carriers of the CACNA1C rs1006737 risk variant exhibit hippocampal and perigenual anterior cingulate (pgACC) dysfunction during episodic memory recall. To test whether this brain systems-level abnormality is a potential intermediate phenotype for psychiatric disorder, we studied unaffected relatives of patients with bipolar disorder, major depression, and schizophrenia...
September 15, 2014: Biological Psychiatry
Bruno Dietsche, Heidelore Backes, Davide Laneri, Thomas Weikert, Stephanie H Witt, Marcella Rietschel, Jens Sommer, Tilo Kircher, Axel Krug
BACKGROUND: Genome-wide association studies have identified the CACNA1C single nucleotide polymorphism (SNP) rs1006737 as one of the most consistent genetic findings as susceptibility locus for major psychiatric disorders. Furthermore, animal and genetic imaging studies have reported strong functional evidence for the association of CACNA1C with learning, memory, neural plasticity, and its association with the hippocampal formation. In the present study we investigated the impact of the CACNA1C SNP rs1006737 on the fractional anisotropy (FA) in the hippocampal formation as well as on verbal learning and memory in healthy individuals...
April 1, 2014: NeuroImage
Axel Krug, Stephanie H Witt, Heidelore Backes, Bruno Dietsche, Vanessa Nieratschker, N Jon Shah, Markus M Nöthen, Marcella Rietschel, Tilo Kircher
The alpha 1C subunit of the L-type voltage-gated calcium channel (CACNA1C) gene is one of the best replicated susceptibility loci for bipolar disorder, schizophrenia and major depression. It is involved in learning, memory and brain plasticity. Genetic studies using functional magnetic resonance imaging (fMRI) reported evidence of association with the CACNA1C single nucleotide polymorphism rs1006737 with functional correlates of episodic memory encoding and retrieval, especially activations in the hippocampus...
March 2014: European Archives of Psychiatry and Clinical Neuroscience
Ilaria Guella, Adolfo Sequeira, Brandi Rollins, Linda Morgan, Federica Torri, Theo G M van Erp, Richard M Myers, Jack David Barchas, Alan F Schatzberg, Stanley J Watson, Huda Akil, William E Bunney, Steven G Potkin, Fabio Macciardi, Marquis P Vawter
MicroRNAs (miRNAs) are small non-coding RNAs that act as potent regulators of gene expression. A recent GWAS reported the rs1625579 SNP, located downstream of miR-137, as the strongest new association with schizophrenia [Ripke S, Sanders AR, Kendler KS, Levinson DF, Sklar P, Holmans PA, et al. Genome-wide association study identifies five new schizophrenia loci. Nat Genet 2011;43:969-76.]. Prior to this GWAS finding, a schizophrenia imaging-genetic study found miR-137 target genes significantly enriched for association with activation in the dorsolateral prefrontal cortex (DLPFC) [Potkin SG, Macciardi F, Guffanti G, Fallon JH, Wang Q, Turner JA, et al...
September 2013: Journal of Psychiatric Research
M Li, X-J Luo, M Rietschel, C M Lewis, M Mattheisen, B Müller-Myhsok, S Jamain, M Leboyer, M Landén, P M Thompson, S Cichon, M M Nöthen, T G Schulze, P F Sullivan, S E Bergen, G Donohoe, D W Morris, A Hargreaves, M Gill, A Corvin, C Hultman, A W Toga, L Shi, Q Lin, H Shi, L Gan, A Meyer-Lindenberg, D Czamara, C Henry, B Etain, J C Bis, M A Ikram, M Fornage, S Debette, L J Launer, S Seshadri, S Erk, H Walter, A Heinz, F Bellivier, J L Stein, S E Medland, A Arias Vasquez, D P Hibar, B Franke, N G Martin, M J Wright, B Su
Bipolar disorder (BD) is a polygenic disorder that shares substantial genetic risk factors with major depressive disorder (MDD). Genetic analyses have reported numerous BD susceptibility genes, while some variants, such as single-nucleotide polymorphisms (SNPs) in CACNA1C have been successfully replicated, many others have not and subsequently their effects on the intermediate phenotypes cannot be verified. Here, we studied the MDD-related gene CREB1 in a set of independent BD sample groups of European ancestry (a total of 64,888 subjects) and identified multiple SNPs significantly associated with BD (the most significant being SNP rs6785[A], P=6...
April 2014: Molecular Psychiatry
Frieder M Paulus, Johannes Bedenbender, Sören Krach, Martin Pyka, Axel Krug, Jens Sommer, Miriam Mette, Markus M Nöthen, Stephanie H Witt, Marcella Rietschel, Tilo Kircher, Andreas Jansen
BACKGROUND: Genome-wide association studies have identified the rs1006737 single nucleotide polymorphism (SNP) in the CACNA1C gene as a susceptibility locus for schizophrenia and bipolar disorder. On the neural systems level this association is explained by altered functioning of the dorsolateral prefrontal cortex (DLPFC) and the hippocampal formation (HF), brain regions also affected by mental illness. In the present study we investigated the association of rs1006737 genotype with prefrontal activation and fronto-hippocampal connectivity...
April 2014: Human Brain Mapping
Shambhu Bhat, David T Dao, Chantelle E Terrillion, Michal Arad, Robert J Smith, Nikolai M Soldatov, Todd D Gould
One of the most consistent genetic findings to have emerged from bipolar disorder genome wide association studies (GWAS) is with CACNA1C, a gene that codes for the α(1C) subunit of the Ca(v)1.2 voltage-dependent L-type calcium channel (LTCC). Genetic variation in CACNA1C have also been associated with depression, schizophrenia, autism spectrum disorders, as well as changes in brain function and structure in control subjects who have no diagnosable psychiatric illness. These data are consistent with a continuum of shared neurobiological vulnerability between diverse-Diagnostic and Statistical Manual (DSM) defined-neuropsychiatric diseases...
October 2012: Progress in Neurobiology
Márcio Gerhardt Soeiro-de-Souza, Maria Concepción Garcia Otaduy, Carolina Zadres Dias, Danielle S Bio, Rodrigo Machado-Vieira, Ricardo Alberto Moreno
INTRODUCTION: Impairments in facial emotion recognition (FER) have been reported in bipolar disorder (BD) during all mood states. FER has been the focus of functional magnetic resonance imaging studies evaluating differential activation of limbic regions. Recently, the α1-C subunit of the L-type voltage-gated calcium channel (CACNA1C) gene has been described as a risk gene for BD and its Met allele found to increase CACNA1C mRNA expression. In healthy controls, the CACNA1C risk (Met) allele has been reported to increase limbic system activation during emotional stimuli and also to impact on cognitive function...
December 1, 2012: Journal of Affective Disorders
Panos Roussos, Stella G Giakoumaki, Anastasios Georgakopoulos, Nikolaos K Robakis, Panos Bitsios
OBJECTIVES: The rs10994336 ANK3 and rs1006737 CACNA1C genetic variants have recently been identified as the most consistent, genome-wide significant risk factors for bipolar disorder, while the CACNA1C variant has also been associated with schizophrenia and major depression. The aim of this study was to examine the phenotypic consequences of the risk CACNA1C and ANK3 alleles in a large homogeneous cohort of healthy young males. METHODS: We recruited 703 randomly selected, healthy army conscripts (mean age 22...
May 2011: Bipolar Disorders
Barbara Franke, Alejandro Arias Vasquez, Joris A Veltman, Han G Brunner, Mark Rijpkema, Guillén Fernández
BACKGROUND: Genetic variation in CACNA1C has been repeatedly shown to increase risk for psychiatric disorders, with the strongest evidence for involvement in bipolar disorder. To elucidate the mechanisms by which such effects on psychiatric disease are brought about by genetic factors, we investigated the influence of CACNA1C polymorphisms on brain structure. METHODS: In 585 healthy volunteers, for whom magnetic resonance imaging data at 1.5 T (n = 282) or 3 T (n = 304) were available, we tested 193 single nucleotide polymorphisms (SNPs) in or near CACNA1C for association with FSL FIRST-segmented subcortical brain structures and hippocampus as well as SPM5-derived total brain volume and global gray and white matter volume using PLINK...
September 15, 2010: Biological Psychiatry
Sven Moosmang, Nicole Haider, Norbert Klugbauer, Helmuth Adelsberger, Nicolas Langwieser, Jochen Müller, Michael Stiess, Else Marais, Verena Schulla, Lubica Lacinova, Sandra Goebbels, Klaus-Armin Nave, Daniel R Storm, Franz Hofmann, Thomas Kleppisch
Current knowledge about the molecular mechanisms of NMDA receptor (NMDAR)-independent long-term potentiation (LTP) in the hippocampus and its function for memory formation in the behaving animal is limited. NMDAR-independent LTP in the CA1 region is thought to require activity of postsynaptic L-type voltage-dependent Ca2+ channels (Cav1.x), but the underlying channel isoform remains unknown. We evaluated the function of the Cav1.2 L-type Ca2+ channel for spatial learning, synaptic plasticity, and triggering of learning-associated biochemical processes using a mouse line with an inactivation of the CACNA1C (Cav1...
October 26, 2005: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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