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Wei Chen, Xiayu Xia, Nan Song, Ying Wang, Hua Zhu, Wei Deng, Qi Kong, Xianmin Pan, Chuan Qin
BACKGROUND: Mouse has been extensively used as a tool for investigating the onset and development of human neurological disorders. As a first step to construct a transgenic mouse model of human brain lesions, it is of fundamental importance to clarify the similarity and divergence of genetic background between non-diseased human and mouse brain tissues. METHODS: We systematically compared, based on large scale integrated microarray data, the transcriptomes of three anatomically distinct brain regions; prefrontal cortex (PFC), hippocampus (HIP) and striatum (STR), across human and mouse...
2016: PloS One
L Guo, F Liu, S Chen, X Yang, J Huang, J He, C E Jaquish, Q Zhao, C C Gu, J E Hixson, D Gu
The current study comprehensively examined the association between common variants in the Na(+)-coupled bicarbonate transporter (NCBT) genes and blood pressure (BP) responses to dietary sodium intervention. A 7-day low-sodium followed by a 7-day high-sodium dietary intervention was conducted among 1906 Han participants from rural areas of northern China. Nine BP measurements were obtained at baseline and each intervention using a random-zero sphygmomanometer. A mixed-effect model was used to assess the additive associations of 76 common variants in five NCBT genes, including SLC4A4, SLC4A5, SLC4A7, SLC4A8 and SLC4A10, with salt sensitivity phenotypes...
September 2016: Journal of Human Hypertension
Deng-Ke Wang, Ying Liu, Evan J Myers, Yi-Min Guo, Zhang-Dong Xie, De-Zhi Jiang, Jia-Min Li, Jichun Yang, Mugen Liu, Mark D Parker, Li-Ming Chen
The SLC4 genes are all capable of producing multiple variants by alternative splicing or using alternative promoters. The physiological consequences of such diversity are of great interest to investigators. Here, we identified two novel variants of the electroneutral Na(+)/HCO3- cotransporter NBCn1, one full-length starting with "MIPL" and the other Nt-truncated starting with "MDEL". Moreover, we identified a new promoter of Slc4a10 encoding NBCn2 and a novel type of Nt-truncated NBCn2 starting with "MHAN"...
2015: Scientific Reports
Anne Sinning, Lutz Liebmann, Christian A Hübner
Slc4a10 is a Na(+)-coupled Cl(-)-HCO3 (-) exchanger, which is expressed in principal and inhibitory neurons as well as in choroid plexus epithelial cells of the brain. Slc4a10 knockout (KO) mice have collapsed brain ventricles and display an increased seizure threshold, while heterozygous deletions in man have been associated with idiopathic epilepsy and other neurological symptoms. To further characterize the role of Slc4a10 for network excitability, we compared input-output relations as well as short and long term changes of evoked field potentials in Slc4a10 KO and wildtype (WT) mice...
2015: Frontiers in Cellular Neuroscience
Luke C Pilling, Roby Joehanes, David Melzer, Lorna W Harries, William Henley, Josée Dupuis, Honghuang Lin, Marcus Mitchell, Dena Hernandez, Sai-Xia Ying, Kathryn L Lunetta, Emelia J Benjamin, Andrew Singleton, Daniel Levy, Peter Munson, Joanne M Murabito, Luigi Ferrucci
INTRODUCTION: Chronically elevated circulating inflammatory markers are common in older persons but mechanisms are unclear. Many blood transcripts (>800 genes) are associated with interleukin-6 protein levels (IL6) independent of age. We aimed to identify gene transcripts statistically mediating, as drivers or responders, the increasing levels of IL6 protein in blood at older ages. METHODS: Blood derived in-vivo RNA from the Framingham Heart Study (FHS, n=2422, ages 40-92 yrs) and InCHIANTI study (n=694, ages 30-104 yrs), with Affymetrix and Illumina expression arrays respectively (>17,000 genes tested), were tested for statistical mediation of the age-IL6 association using resampling techniques, adjusted for confounders and multiple testing...
October 2015: Experimental Gerontology
Christian Aalkjaer, Ebbe Boedtkjer, Inyeong Choi, Soojung Lee
Cation-coupled HCO3(-) transport was initially identified in the mid-1970s when pioneering studies showed that acid extrusion from cells is stimulated by CO2/HCO3(-) and associated with Na(+) and Cl(-) movement. The first Na(+)-coupled bicarbonate transporter (NCBT) was expression-cloned in the late 1990s. There are currently five mammalian NCBTs in the SLC4-family: the electrogenic Na,HCO3-cotransporters NBCe1 and NBCe2 (SLC4A4 and SLC4A5 gene products); the electroneutral Na,HCO3-cotransporter NBCn1 (SLC4A7 gene product); the Na(+)-driven Cl,HCO3-exchanger NDCBE (SLC4A8 gene product); and NBCn2/NCBE (SLC4A10 gene product), which has been characterized as an electroneutral Na,HCO3-cotransporter or a Na(+)-driven Cl,HCO3-exchanger...
October 2014: Comprehensive Physiology
Xiaohong Song, Miwako Yamasaki, Taisuke Miyazaki, Kohtarou Konno, Motokazu Uchigashima, Masahiko Watanabe
Slc4a10 was originally identified as a Na(+) -driven Cl(-) /HCO3 (-) exchanger NCBE that transports extracellular Na(+) and HCO3 (-) in exchange for intracellular Cl(-) , whereas other studies argue against a Cl(-) -dependence for Na(+) -HCO3 (-) transport, and thus named it the electroneutral Na(+) /HCO3 (-) cotransporter NBCn2. Here we investigated Slc4a10 expression in adult mouse brains by in situ hybridization and immunohistochemistry. Slc4a10 mRNA was widely expressed, with higher levels in pyramidal cells in the hippocampus and cerebral cortex, parvalbumin-positive interneurons in the hippocampus, and Purkinje cells (PCs) in the cerebellum...
September 2014: European Journal of Neuroscience
V Belengeanu, T H Gamage, S Farcas, M Stoian, N Andreescu, A Belengeanu, E Frengen, D Misceo
We report a 20-month-old girl ascertained at the age of 11 months for developmental delay. She presented with hypotonia and delayed motor development. The patient had severe language impairment and showed behaviour consistent with autism spectrum disorder. She was microcephalic with mild dysmorphic features and had joint hyperlaxity. We detected a 2.3 Mb de novo deletion in 2q24.2q24.3 on her paternal chromosome. We compare the clinical features of our patient to six previously published patients with a deletion in 2q24...
April 10, 2014: Gene
Sarah F Janssen, Theo Gmf Gorgels, Jacoline B Ten Brink, Nomdo M Jansonius, Arthur Ab Bergen
BACKGROUND: The neuroepithelia of the choroid plexus (CP) in the brain and the ciliary body (CB) of the eye have common embryological origins and share similar micro-structure and functions. The CP epithelium (CPE) and the non-pigmented epithelium (NPE) of the CB produce the cerebrospinal fluid (CSF) and the aqueous humor (AH) respectively. Production and outflow of the CSF determine the intracranial pressure (ICP); production and outflow of the AH determine the intraocular pressure (IOP)...
2014: Fluids and Barriers of the CNS
Inga B Christensen, Tua Gyldenholm, Helle H Damkier, Jeppe Praetorius
The choroid plexus epithelium (CPE) has served as a model-epithelium for cell polarization and transport studies and plays a crucial role for cerebrospinal fluid (CSF) production. The normal luminal membrane expression of Na(+),K(+)-ATPase, aquaporin-1 and Na(+)/H(+) exchanger 1 in the choroid plexus is severely affected by deletion of the slc4a10 gene that encodes the bicarbonate transporting protein Ncbe/NBCn2. The causes for these deviations from normal epithelial polarization and redistribution following specific gene knockout are unknown, but may be significant for basic epithelial cell biology...
2013: Frontiers in Physiology
Henriette L Christensen, An T Nguyen, Fredrik D Pedersen, Helle H Damkier
The choroid plexus epithelium (CPE) is located in the ventricular system of the brain, where it secretes the majority of the cerebrospinal fluid (CSF) that fills the ventricular system and surrounds the central nervous system. The CPE is a highly vascularized single layer of cuboidal cells with an unsurpassed transepithelial water and solute transport rate. Several members of the slc4a family of bicarbonate transporters are expressed in the CPE. In the basolateral membrane the electroneutral Na(+) dependent Cl(-)/HCO3 (-) exchanger, NCBE (slc4a10) is expressed...
2013: Frontiers in Physiology
Ying Liu, Deng-Ke Wang, De-Zhi Jiang, Xue Qin, Zhang-Dong Xie, Qing K Wang, Mugen Liu, Li-Ming Chen
Previous studies have shown that the electroneutral Na(+)/HCO(3) (-) cotransporter NBCn2 (SLC4A10) is predominantly expressed in the central nervous system (CNS). The physiological and pathological significances of NBCn2 have been well recognized. However, little is known about the tissue specificity of expression of different NBCn2 variants. Moreover, little is known about the expression of NBCn2 proteins in systems other than CNS. Here, we identified a set of novel Slc4a10 variants differing from the originally described ones by containing a distinct 5' untranslated region encoding a new extreme amino-terminus (Nt)...
2013: PloS One
Janusz K Rybakowski
Mood stabilizers form a cornerstone in the long-term treatment of bipolar disorder. The first representative of their family was lithium, still considered a prototype drug for the prevention of manic and depressive recurrences in bipolar disorder. Along with carbamazepine and valproates, lithium belongs to the first generation of mood stabilizers, which appeared in psychiatric treatment in the 1960s. Atypical antipsychotics with mood-stabilizing properties and lamotrigine, which were introduced in the mid-1990 s, form the second generation of such drugs...
March 2013: CNS Drugs
Gerrit Hilgen, Antje K Huebner, Naoyuki Tanimoto, Vithiyanjali Sothilingam, Christina Seide, Marina Garcia Garrido, Karl-Friedrich Schmidt, Mathias W Seeliger, Siegrid Löwel, Reto Weiler, Christian A Hübner, Karin Dedek
Regulation of ion and pH homeostasis is essential for normal neuronal function. The sodium-driven chloride bicarbonate exchanger NCBE (Slc4a10), a member of the SLC4 family of bicarbonate transporters, uses the transmembrane gradient of sodium to drive cellular net uptake of bicarbonate and to extrude chloride, thereby modulating both intracellular pH (pH(i)) and chloride concentration ([Cl(-)](i)) in neurons. Here we show that NCBE is strongly expressed in the retina. As GABA(A) receptors conduct both chloride and bicarbonate, we hypothesized that NCBE may be relevant for GABAergic transmission in the retina...
2012: PloS One
Helle Hasager Damkier, Jeppe Praetorius
Mutational changes of one transporter can have deleterious effects on epithelial function leaving the cells with the options of either compensating for the loss of function or dedifferentiating. Previous studies have shown that the choroid plexus epithelium (CPE) from mice lacking the Na(+)-dependent Cl(-)/HCO(3)(-) exchanger (NCBE) encoded by Slc4a10 leads to retargeting of the Na(+)/H(+) exchanger 1 (NHE1) from the luminal to the basolateral plasma membrane. We hypothesized that disruption of NCBE, the main basolateral Na(+) importer in the CPE, would lead to a compensatory increase in the abundance of other important transport proteins in this tissue...
May 15, 2012: American Journal of Physiology. Cell Physiology
A Schosser, D Gaysina, S Cohen-Woods, E Domenici, J Perry, F Tozzi, A Korszun, C Gunasinghe, J Gray, L Jones, E B Binder, F Holsboer, N Craddock, M J Owen, I W Craig, A E Farmer, P Muglia, P McGuffin
The High-Throughput Disease-specific target Identification Program (HiTDIP) aimed to study case-control association samples for 18 common diseases. Here we present the results of a follow-up case-control association study of HiTDIP in major depressive disorder (MDD). The HiTDIP in MDD was conducted in a sample of 974 cases of recurrent MDD of white German origin collected at the Max-Planck Institute (MP-GSK) and 968 ethnically matched controls screened for lifetime absence of depression. Six genes were identified as of interest for a follow-up, based on the strength of the association and based on the interest as potential candidate target for developing new treatment for depression: Solute Carrier Family 4 Member 10 (SLC4A10), Dipeptidyl Peptidase IV (DPP4), Dopamine Receptor D3 (DRD3), Zinc Finger Protein 80 (ZNF80), Nitric Oxide Synthase 2A (NOS2A) and Peroxisome Proliferator-Activated Receptor-Gamma, Coactivator 1, Alpha (PPARGC1A)...
September 2011: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Ying Liu, Jiu-Ying Xu, Deng-Ke Wang, Walter F Boron, Li-Ming Chen
The SLC4A10 gene, which is highly expressed in the mammalian brain, contains two known alternative splicing units, inserts A and B, and is theoretically capable of producing four NBCn2 splice variants: NBCn2-A, -B, -C, and -D. By immunoprecipitation and western blotting, a previous study showed the putative NBCn2-D to be expressed predominantly in the subcortex (SCX) and medulla (MD) of mouse brain. However, no evidence has been provided, in any species, for the existence of a full-length transcript encoding NBCn2-D...
May 16, 2011: Brain Research
Ana Cristina Victorino Krepischi, Jeroen Knijnenburg, Debora Romeo Bertola, Chong Ae Kim, Peter Lees Pearson, Emilia Bijlsma, Karoly Szuhai, Fernando Kok, Angela Maria Vianna-Morgante, Carla Rosenberg
Approximately 50% of all carriers of 2q21-q31 deletions present epileptic seizures. The band 2q24 constitutes the smallest commonly deleted segment in these patients, and contains the voltage-gated sodium channel genes SCN1A and SCN2A, associated with Dravet syndrome and benign familial neonatal-infantile seizures, respectively. A further putative locus involving epilepsy in the region was previously identified through disruption of the SLC4A10 gene by translocation. In the course of performing high-resolution DNA copy number analyses on syndromic mentally impaired individuals, we encountered three patients with overlapping deletions in chromosome region 2q24...
December 2010: Epilepsia
Helle Hasager Damkier, Christian Aalkjaer, Jeppe Praetorius
The slc4a10 gene encodes an electroneutral Na(+)-dependent HCO(3)(-) importer for which the precise mode of action remains unsettled. To resolve this issue, intracellular pH (pH(i)) recordings were performed upon acidification in the presence of CO(2)/HCO(3)(-) by 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF) fluorometry of stably slc4a10-transfected NIH-3T3 fibroblasts. slc4a10 expression induced a significant Na(+)-dependent pH(i) recovery, which was accompanied by an increase in the intracellular Na(+) concentration evaluated by use of the Na(+)-sensitive fluorophore CoroNa Green...
August 27, 2010: Journal of Biological Chemistry
Y Liu, K Xu, L M Chen, X Sun, M D Parker, M L Kelly, J C LaManna, W F Boron
The five known Na-coupled HCO(3)(-) transporters (NCBTs) of the solute carrier 4 (SLC4) family play important roles in pH regulation and transepithelial HCO(3)(-) transport. Nearly all of the NCBTs have multiple splice variants. One particular NCBT, the electroneutral Na/HCO(3)(-) cotransporter NBCn2 (SLC4A10), which is predominantly expressed in brain, has three known splice variants-NBCn2-A, -B, and -C-as well as a potential variant-D. It is important to know the tissue-specific expression of the splice variants for understanding the physiological roles of NBCn2 in central nervous system...
September 1, 2010: Neuroscience
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