Advertisement

RNA Microarray analysis of channels and transporters in normal and fetal Down Syndrome (trisomy 21) brain

  • G. Lubec
  • S. Y. Sohn
Part of the Journal of Neural Transmission Supplement 67 book series (NEURAL SUPPL, volume 67)

Summary

A couple of transporters and channels has been proposed as candidate genes involved in the pathomechanisms leading to the neurodevelopmental abnormalities and the phenotype of Down Syndrome (DS, trisomy 21). No systematic study, however, has been carried out showing the concomitant expression of several candidate RNAs during fetal life.

It was therefore the aim of the study to apply an array of 96 brain RNAs mainly consisting of channels and transporters to show their expressional levels in fetal DS brain at the early second trimester.

Brain RNA was extracted from fetal cortex of the 18–19th week of gestation of controls and DS individuals and used for the GEArray Q Series Human Neuroscience-1 / Ion Channels & Transporters analysis.

15 out of 96 RNAs of the array were observed on the films in both groups during this gestational period consisting of genes for potassium, sodium, calcium channels and transporters (ASIC3, ATP1B1, CACNA1B, KCNB2, KCNC1, KCND2, KCNF1, KCNN1, KCNN3, hKCa4, KCNQ2, lipid transfer protein II, SCN2B, acetyl choline transporter, glutamate transporter3).

There was no statistically significant difference between the control and the DS group.

We provide information on the developmental expression of the aforementioned 15 RNAs and the absence of the residual examined 81 RNAs at the 18th/19th week of gestation in fetal cortex that was never reported before and show that channels and transporters present with unchanged expression in fetal DS brain.

Keywords

Down Syndrome Dorsal Root Ganglion Neuron Serotonin Transporter Glutamate Transporter Phospholipid Transfer Protein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Adamson CL, Reid MA, Mo ZL, Bowne-English J, Davis RL (2002) Firing features and potassium channel content of murine spiral ganglion neurons vary with cochlear location. J Comp Neurol 447: 331–350PubMedCrossRefGoogle Scholar
  2. Benn SC, Costigan M, Tate S, Fitzgerald M, Woolf CJ (2001) Developmental expression of the TTX-resistant voltage-gated sodium channels Nav1.8 (SNS) and Nav1.9 (SNS2) in primary sensory neurons. J Neurosci 21: 6077–6085PubMedGoogle Scholar
  3. Castaldo P, del Giudice EM, Coppola G, Pascotto A, Annunziato L, Taglialatela M (2002) Benign familial neonatal convulsions caused by altered gating of KCNQ2/ KCNQ3 potassium channels. J Neurosci 22: RC199Google Scholar
  4. Caviedes P, Ault B, Rapoport SI (1990) The role of altered sodium currents in action potential abnormalities of cultured dorsal root ganglion neurons from trisomy 21 ( Down syndrome) human fetuses. Brain Res 510: 229–236PubMedCrossRefGoogle Scholar
  5. Chen CC, Zimmer A, Sun WH, Hall J, Brownstein MJ, Zimmer A (2002) A role for ASIC3 in the modulation of high-intensity pain stimuli. Proc Natl Acad Sci USA 99: 8992–8997PubMedGoogle Scholar
  6. Cowley EA, Linsdell P (2002) Characterization of basolateral K+ channels underlying anion secretion in the human airway cell line Calu-3. J Physiol 538: 747–757PubMedCrossRefGoogle Scholar
  7. Engidawork E, Roberts JC, Hardmeier R, Scheper RJ, Lubec G (2002) Expression of the multidrug resistance P glycoprotein (Pgp) and multidrug resistance associated protein (MRP1) in Down syndrome brains. J Neural Transm [Suppl] 61: 35–45Google Scholar
  8. Fields RD (1998) Effects of ion channel activity on development of dorsal root ganglion Neurons. J Neurobiol 37: 158–170PubMedCrossRefGoogle Scholar
  9. Gastaldi M, Robaglia-Schlupp A, Massacrier A, Planells R, Cau P (1998) mRNA coding for voltage-gated sodium channel beta2 subunit in rat central nervous system: cellular distribution and changes following kainate-induced seizures. Neurosci Lett 249: 53–56PubMedCrossRefGoogle Scholar
  10. Gosset P, Ghezala GA, Korn B, Yaspo ML, Poutska A, Lehrach H, Sinet PM, Creau N (1997) A new inward rectifier potassium channel gene (KCNJ15) localized on chromosome 21 in the Down syndrome chromosome region 1 (DCR1). Genomics 44: 237–241PubMedCrossRefGoogle Scholar
  11. Gulesserian T, Engidawork E, Cairns N, Lubec G (2000) Increased protein levels of serotonin transporter in frontal cortex of patients with Down syndrome. Neurosci Lett 296: 53–57PubMedCrossRefGoogle Scholar
  12. Gurantz D, Ribera AB, Spitzer NC (1996) Temporal regulation of Shaker-and Shab-like potassium channel gene expression in single embryonic spinal neurons during K+ current development. J Neurosci 16: 3287–3295PubMedGoogle Scholar
  13. Hagiwara T, Tanaka K, Takai S, Maeno-Hikichi Y, Mukainaka Y, Wada K (1996) Genomic organization, promoter analysis, and chromosomal localization of the gene for the mouse glial high-affinity glutamate transporter Slcla3. Genomics 33: 508–515PubMedCrossRefGoogle Scholar
  14. Haug K, Sander T, Hallmann K, Rau B, Dullinger JS, Elger CE, Propping P, Heils A (2000) The voltage-gated sodium channel beta2-subunit gene and idiopathic generalized epilepsy. Neuroreport 11: 2687–2689PubMedCrossRefGoogle Scholar
  15. Karschin C, Karschin A (1997) Ontogeny of gene expression of Kir channel subunits in the rat. Mol Cell Neurosci 10: 131–148PubMedCrossRefGoogle Scholar
  16. Kawashima N, Takamiya K, Sun J, Kitabatake A, Sobue K (1997) Differential expression of isoforms of PSD-95 binding protein (GKAP/SAPAP1) during rat brain development. FEBS Lett 418: 301–304PubMedCrossRefGoogle Scholar
  17. Kim SH, Fountoulakis M, Cairns NJ, Lubec G (2002) Human brain nucleoside diphosphate kinase activity is decreased in Alzheimer’s disease and Down syndrome. Biochem Biophys Res Commun 296: 970–975PubMedCrossRefGoogle Scholar
  18. Kish S, Karlinsky H, Becker L, Becker J, Gilbert J, Rebbetoy M, Chang LJ, DiStefano L, Hornykiewicz O (1989) Down’s syndrome individuals begin life with normal levels of brain cholinergic markers. J Neurochem 52: 1183–1187PubMedCrossRefGoogle Scholar
  19. Krapfenbauer K, Yoo BC, Kim SH, Cairns N, Lubec G (2001) Differential display reveals downregulation of the phospholipid transfer protein ( PLTP) at the mRNA level in brains of patients with Down syndrome. Life Sci 68: 2169–2179PubMedCrossRefGoogle Scholar
  20. Lubec B, Yoo BC, Dierssen M, Balic N, Lubec G (2001) Down syndrome patients start early prenatal life with normal cholinergic, monoaminergic and serotoninergic innervation. J Neural Transm [Suppl] 61: 303–310Google Scholar
  21. Malo MS, Srivastava K, Ingram VM (1995) Gene assignment by polymerise chain reaction: localization of the human potassium channel IsK gene to the Down’s syndrome region of chromosome 21q22.1-q22.2. Gene 159: 273–275PubMedCrossRefGoogle Scholar
  22. Nagamine K, Kudoh J, Minoshima S, Kawasaki K, Asakawa S, Ito F, Shimizu N (1998) Molecular cloning of a novel putative Ca2+ channel protein (TRPC7) highly expressed in brain. Genomics 54: 124–131PubMedCrossRefGoogle Scholar
  23. Ohira M, Seki N, Nagase T, Suzuki E, Nomura N, Ohara O, Hattori M, Sakaki Y, Eki T, Murakami Y, Saito T, Ichikawa H, Ohki M (1997) Gene identification in 1.6-Mb region of the Down syndrome region on chromosome 21. Genome Res 7: 47–58PubMedCrossRefGoogle Scholar
  24. Risser D, Lubec G, Cairns N, Herrera-Marschitz M (1997) Excitatory amino acids and monoamines in parahippocampal gyrus and frontal cortical pole of adults with Down syndrome. Life Sci 60: 1231–1237PubMedCrossRefGoogle Scholar
  25. Ritsner M, Modai I, Ziv H, Amir S, Halperin T, Weizman A, Navon R (2002) An association of CAG repeats at the KCNN3 locus with symptom dimensions of schizophrenia. Biol Psychiatry 51: 788–794PubMedCrossRefGoogle Scholar
  26. Sakura H, Bond C, Warren-Perry M, Horsley S, Kearney L, Tucker S, Adelman J, Turner R, Ashcroft FM (1995) Characterization and variation of a human inwardlyrectifying-K-channel gene (KCNJ6): a putative ATP-sensitive K-channel subunit. FEBS Lett 367: 193–197PubMedCrossRefGoogle Scholar
  27. Schmukler BE, Bond CT, Wilhelm S, Bruening-Wright A, Maylie J, Adelman JP, Alper SL (2001) Structure and complex transcription pattern of the mouse SKl K(Ca) channel gene, KCNN1. Biochim Biophys Acta 1518: 36–46Google Scholar
  28. Schneider C, Risser D, Kirchner L, Kitzmueller E, Cairns N, Prast H, Singewald N, Lubec G (1997) Similar deficits of central histaminergic system in patients with Down syndrome and Alzheimer disease. Neurosci Lett 222: 183–186PubMedCrossRefGoogle Scholar
  29. Scott BS, Petit TL, Becker LE, Edwards BA (1981) Abnormal electric membrane properties of Down’s syndrome DRG neurons in cell culture. Brain Res 254: 257–270PubMedGoogle Scholar
  30. Shuck ME, Piser TM, Bock JH, Slightom JL, Lee KS, Bienkowski MJ (1997) Cloning and characterization of two K+ inward rectifier (Kir) 1.1 potassium channel homologs from human kidney (Kir1.2 and Kir1.3). J Biol Chem 272: 586–593PubMedCrossRefGoogle Scholar
  31. Shull MM, Pugh DG, Lane LK, Lingrel JB (1990) MspI and PvuII polymorphisms in the Na,K-ATPase beta subunit gene ATP1B1. Nucl Acids Res 18: 1087PubMedCrossRefGoogle Scholar
  32. Stubbs L, Richik EM, Goldberg E, Rudy B, Handel MA, Johnson D (1994) Clustering of six human 11p15 gene homologs within a 500-kb interval of proximal mouse chromosome 7. Genomics 24: 324–332PubMedCrossRefGoogle Scholar
  33. Tanizawa Y, Matsubara A, Ueda K, Katagiri H, Kuwano A, Ferrer J, Permutt MA, Oka Y (1996) A human pancreatic islet inwardly rectifying potassium channel: cDNA cloning, determination of the genomic structure and genetic variations in Japanese NIDDM patients. Diabetologia 39: 447–452PubMedCrossRefGoogle Scholar
  34. Thiery E, Gosset P, Damotte D, Delezoide AL, de Saint Sauveur N, Vayssettes C, Creau N (2000) Developmentally regulated expression of the murine ortholog of the potassium channel KIR4.2 (KCNJ15). Mech Dev 95: 313–316PubMedCrossRefGoogle Scholar
  35. Tinel N, Lauritzen I, Chouabe C, Lazdunski M, Borsotto M (1998) The KCNQ2 potassium channel: splice variants, functional and developmental expression. Brain localization and comparison with KCNQ3. FEBS Lett 438: 171–176PubMedCrossRefGoogle Scholar
  36. Tsaur ML, Menzel S, Lai FP, Espinosa 3rd R, Concannon P, Spielman RS, Hanis CL, Cox NJ, Le Beau MM, German MS, et al. (1995) Isolation of a cDNA clone encoding a KATP channel-like protein expressed in insulin-secreting cells, localization of the human gene to chromosome band 21q22.1, and linkage studies with NIDDM. Diabetes 44: 592–596Google Scholar
  37. Wymore RS, Korenberg JR, Kinoshita KD, Aiyar J, Coyne C, Chen XN, Hustad CM, Copeland NG, Gutman GA, Jenkins NA, Chandy KG (1994) Genomic organization, nucleotide sequence, biophysical properties, and localization of the voltage-gated K+ channel gene KCNA4/Kv1.4 to mouse chromosome 2/human 11p14 and mapping of KCNC1/Kv3.1 to mouse 7/human 11p14.3—p15.2 and KCNA1/Kv1.1 to human 12p13. Genomics 20: 191–202PubMedCrossRefGoogle Scholar
  38. Yamakawa K, Mitchell S, Hubert R, Chen XN, Colbern S, Huo YK, Gadomski C, Kim UJ, Korenberg JR (1995) Isolation and characterization of a candidate gene for progressive myoclonus epilepsy on 21q22.3. Hum Mol Genet 4: 709–716PubMedCrossRefGoogle Scholar
  39. Zhu XR, Wulf A, Schwarz M, Isbrandt D, Pongs 0 (1999) Characterization of human Kv4.2 mediating a rapidly-inactivating transient voltage-sensitive K+ current. Receptors Channels 6: 387–400PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • G. Lubec
    • 1
    • 2
  • S. Y. Sohn
    • 1
  1. 1.Department of PediatricsUniversity of ViennaAustria
  2. 2.CChem, FRSC (UK), Department of PediatricsUniversity of ViennaViennaAustria

Personalised recommendations