Pediatric Neurology
Volume 33, Issue 4 , Pages 235-243 , October 2005

Lithium Citrate for Canavan Disease

  • Christopher G. Janson, MD

      Affiliations

    • Department of Neurosurgery and Molecular Genetics, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Camden, New Jersey
    • Department of Neurology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Camden, New Jersey
    • Division of Neuroradiology, University of Pennsylvania Medical Center and Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
    • Corresponding Author InformationCommunications should be addressed to: Dr. Janson; The Cell and Gene Therapy Center; 401 Haddon Avenue, Suite #388; Camden, NJ 08103.
    • ,
  • Mitra Assadi, MD

      Affiliations

    • Department of Neurology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Camden, New Jersey
    • ,
  • Jeremy Francis, PhD

      Affiliations

    • Department of Neurosurgery and Molecular Genetics, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Camden, New Jersey
    • ,
  • Larissa Bilaniuk, MD

      Affiliations

    • Division of Neuroradiology, University of Pennsylvania Medical Center and Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
    • ,
  • David Shera, ScD

      Affiliations

    • Department of Biostatistics, University of Pennsylvania Medical Center and Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
    • ,
  • Paola Leone, PhD

      Affiliations

    • Department of Neurosurgery and Molecular Genetics, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Camden, New Jersey
    • Division of Neuroradiology, University of Pennsylvania Medical Center and Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania

Received 26 January 2005 ,Accepted 4 April 2005.

References 

  1. Baslow M . Brain N-acetylaspartate as a molecular water pump and its role in the etiology of Canavan disease (A mechanistic explanation) . J Mol Neurosci . 2003;21:185–190
  2. Taylor DL , Davies SEC , Obrenovitch TP , et al.   Investigation into the role of NAA in cerebral osmoregulation . J. Neurochem . 1995;65:275–281
  3. D’Adamo AF , Yatsu FM . Acetate metabolism in the nervous system (NAA and the biosynthesis of brain lipids) . J Neurochem . 1965;13:961–965
  4. Mehta V , Namboodiri MAA . NAA as an acetyl source in the nervous system . Molec Brain Res . 1995;21:151–157
  5. Birken DL , Oldendorf WH . N-acteyl-l-aspartic acid (A literature review of a compound prominent in proton spectroscopic studies of brain) . Neurosci Biobehav Rev . 1989;13:23–31
  6. Clark JB . N-acetyl-aspartate (A marker for neuronal loss or mitochondrial dysfunction) . Dev Neurosci . 1998;20:271–276
  7. Tallan HH . Studies on the distribution of NAA in brain . J. Biol. Chem . 1957;224:41–45
  8. Patel TB , Clark JB . Synthesis of NAA by rat brain mitochondria and its involvement in mitochondrial/cytosolic carbon transport . Biochem J . 1979;184:539–546
  9. Moffett JR , Namboodiri MA , Cangro C , Heale J . Immunohistochemical localization of NAA in the rat brain . Neuroreport . 1991;2:131–134
  10. Lu ZH , Chakraborty G , Ledeen RW , Yahya D , Wu G . N-Acetylaspartate synthase is bimodally expressed in microsomes and mitochondria of brain . Brain Res Mol Brain Res . 2004;122:71–78
  11. Leone P , Janson CG , McPhee SJ , During MJ . Global CNS gene transfer for a childhood neurogenetic enzyme deficiency (Canavan disease) . Curr Opin Molec Ther . 2001;1:487–491
  12. Baslow MH . Molecular water pumps and the etiology of Canavan disease (A case of the sorcerer’s apprentice) . J Inher Metab Dis . 1999;22:99–101
  13. Rubin Y , LaPlaca MC , Smith DH , Thibault LE , Lenkinski RE . The effect of NAA on the intracellular free calcium level in NTera2 neurons . Neurosci Lett . 1995;198:209–212
  14. Westbrook GL , Mayer ML , Namboodiri MA , Neale JH . High concentrations of NAAG selectively activate NMDA receptors on mouse spinal cord neurons in cell culture . J Neurosci . 1986;6:3385–3392
  15. Plis L , Fitzgibbon T , Balcar VJ , Stastny F . Neurotoxicity of NAAG in vivo is sensitive to NMDA antagonists and mGluRII ligands . Neuroreport . 2000;11:3651–3654
  16. Chakraborty G , Mekala P , Yahya D , Wu G , Ledeen RW . Intraneuronal N-acetylaspartate supplies acetyl groups for myelin lipid synthesis (Evidence for myelin-associated aspartoacylase) . Neurochem . 2001;78:736–745
  17. Kitada K , Akimitsu T , Shigematsu Y , et al.   Accumulation of N-acetyl-l-aspartate in the brain of the tremor rat, a mutant exhibiting absence-like seizure and spongiform degeneration in the central nervous system . J Neurochem . 2000;74:2512–2519
  18. Akimitsu T , Kurisu K , Hanaya R , et al.   Epileptic seizures induced by N-acetyl-l-aspartate in rats (In vivo and in vitro studies) . Brain Res . 2000;861:143–150
  19. Yan HD , Ishihara K , Serikawa T , Sasa M . Activation by N-acetyl-l-aspartate of acutely dissociated hippocampal neurons in rats via metabotropic glutamate receptors . Epilepsia . 2003;44:1153–1159
  20. Urenjak J , Williams SR , Gadian DG , Noble M . Specific expression of NAA in neurons, oligodendrocyte-type-2 astrocyte precursors, and immature oligodendrocytes in vitro . J Neurochem . 1992;59:55–61
  21. Sager TN , Thomsen C , Valsborg JS , Laursen H , Hansen AJ . Astroglia contain a specific transport mechanism for NAA . J Neurochem . 1999;73:807–811
  22. Baslow MH , Suckow RF , Hungund BL . Effects of ethanol and of alcohol dehydrogenase inhibitors on the reduction of N-acetylaspartate levels of brain in mice in vivo (A search for substances that may have therapeutic value in the treatment of Canavan disease) . J Inherit Metab Dis . 2000;23:684–692
  23. Baslow MH , Suckow RF , Sapirstein V , Hungund BL . Expression of aspartoacylase activity in cultured rat macroglial cells is limited to oligodendrocytes . J Mol Neurosci . 1999;13(1-2):47–53
  24. Kimani BF , Jacobowitz DM , Kallarakal AT , Namboodiri MAA . ASPA is restricted primarily to myelin-synthesizing cells in the CNS (Therapeutic implications for Canavan disease) . Molec Brain Res . 2002;107:176–182
  25. Kimani BF , Jacobowitz DM , Namboodiri MAA . Developmental increase of ASPA in oligodendrocytes parallels CNS myelination . Dev Brain Res . 2003;140:105–115
  26. Madhavarao CN , Moffett JR , Moore RA , Viola RE , Namboodiri MAA , Jacobowitz DM . Immunohistochemical localization of ASPA in the rat central nervous system . J Comp Neurol . 2004;472:318–329
  27. Bhakoo KK , Craig TJ , Styles P . Developmental and regional distribution of ASPA in rat brain tissue . J Neurochem . 2001;79:211–220
  28. Baslow M , Kitada K , Suckow RF , Hungund BL , Serikawa T . The effects of lithium chloride and other substances on levels of brain NAA in Canavan disease-like rats . Neurochem Res . 2002;27:403–406
  29. O’Donnell T , Rotzinger S , Nakashima TT , Hanstock CC , Ulrich M , Silverstone PH . Chronic lithium and sodium valproate both decrease the concentration of myoinositol and increase the concentration of inositol monophosphates in rat brain . Brain Res . 2000;880:84–91
  30. McPhee SW, Francis J, Janson CG, Serikawa T, Hyland K, Ong EO, et al. Effects of AAV-2-mediated aspartoacylase gene transfer in the tremor rat model of Canavan disease . Brain Res Mol Brain Res . 2005;135(1-2):112–121
  31. Moore GJ , Bebchuk JM , Hasanat K , et al.   Lithium increases NAA in the human brain (In vivo evidence in support of bcl-2 neurotrophic effects?) . Biol Psychiatry . 2000;48:1–8
  32. Brambilla P, Stanley JA, Sassi RB, Nicoletti MA, Mallinger AG, Keshavan MS, et al. MRS study of dorsolateral prefrontal cortex in healthy individuals before and after lithium administration . Neuropsychopharmacology . 2004;29:1918–1924
  33. Silverstone P , Wu RH , O’Donnell T , Ulrich M , Asghar SJ , Hanstock CC . Chronic treatment with lithium, but not sodium valproate, increases cortical NAA in euthymic bipolar patients . Int Clin Psychopharmacol . 2003;18:73–79
  34. Nonaka S , Hough CJ , Chuang DM . Chronic lithium treatment robustly protects neurons in the central nervous system against excitotoxicity by inhibiting NMDA receptor-mediated calcium influx . Proc Natl Acad Sci USA . 1998;95:2642–2647
  35. Berridge MJ , Downes CP , Hanley MR . Lithium amplifies agonist-dependent phosphatidylinositol responses in brain and salivary glands . Biochem J . 1982;206:587–595
  36. Chalenka-Franaszek E , Chuang D . Lithium activates the serine/threonine kinase Akt-1 and suppresses glutamate-induced inhibition of Akt-1 activity in neurons . Proc Natl Acad Sci USA . 1999;96:8745–8750
  37. Joseph NE , Renshaw PF , Leigh JS . Systemic lithium administration alters rat cerebral cortex phospholipids . Biol Psychiatry . 1987;22:540–544
  38. Chen R , Chuang D . Long term lithium treatment suppresses p53 and Bax expression but increases Bcl-2 expression . Proc Natl Acad Sci USA . 1999;274:6039–6042
  39. Klein PS , Melton DA . A molecular mechanism (GSK) for the effect of lithium on development . Proc Natl Acad Sci USA . 1996;93:8455–8459
  40. Phiel CJ , Klein PS . Molecular targets of lithium action . Ann Rev Pharmacol Toxicol . 2001;41:789–813
  41. Moore GJ , Bebchuk JM , Wilds IB , Chen G , Manji HK . Lithium-induced increase in human brain grey matter . Lancet . 2000;356:1241–1242
  42. Kim JS , Chang MY , Yu IT , et al.   Lithium selectively increases neuronal differentiation of hippocampal neural progenitor cells in vitro and in vivo . J Neurochem . 2004;89:324–336
  43. Hashimoto R , Senatorov V , Kanai H , Leeds P , Chuang DM . Lithium stimulates progenitor cell proliferation in cultured brain neurons . Neuroscience . 2003;117:55–61
  44. Chuang DM . Neuroprotective and neurotrophic effects of the mood stabilizer lithium (Can it be used to treat neurodegenerative diseases?) . Crit Rev Neurobiol . 2004;16:83–90
  45. Chan JR , Watkins TA , Cosgaya JM , et al.   NGF controls axonal receptivity to myelination by Schwann cells or oligodendrocytes . Neuron . 2004;43:183–191
  46. Tolwani RJ , Cosgaya JM , Varma S , Jacob R , Kuo LE , Shooter EM . BDNF overexpression produces a long-term increase in myelin formation in the peripheral nervous system . J Neurosci Res . 2004;77:662–669
  47. Cohen RI , Marmur R , Norton WT , Mehler MF , Kessler JA . Nerve growth factor and neurotrophin-3 differentially regulate the proliferation and survival of developing rat brain oligodendrocytes . J Neurosci . 1996;16:6433–6442
  48. Tarnopolsky MA , Beal MF . Potential for creatine and other therapies targeting cellular energy dysfunction in neurological disorders . Ann Neurol . 2001;49:561–574
  49. Peluso G , Barbarisi A , Savica V , et al.   Carnitine (An osmolyte that plays a metabolic role) . J. Cellular Biochem . 2000;80:1–10
  50. Janson C , McPhee SWJ , Bilaniuk L , et al.   Gene therapy of Canavan disease (AAV2 vector for neurosurgical delivery of aspartoacylase gene (ASPA) to the human brain) . Human Gene Therapy . 2002;13:1391–1412
  51. Barkovich AJ , Kjos BO , Jackson DE , Norman D . Normal maturation of the neonatal and infant brain (MR imaging at 1.5 T) . Radiology . 1988;166:173–180
  52. Kingsley PB . Methods of measuring Spin-Lattice (T1) relaxation times (An annotated bibliography) . Concepts Magn Reson . 1999;11:243–276
  53. Steen RG , Ogg RJ , Reddick WE , Kingsley PB . Age-related changes in the pediatric brain (Quantitative MR evidence of maturational changes during adolescence) . Am J Neuroradiol . 1997;18:819–828
  54. McArdle CB , Richardson CJ , Nicholas DA , Mirfakhraee M , Hayden CK , Amparo EG . Developmental features of the neonatal brain (MR imaging) . Part I. Gray-white matter differentiation and myelination, Radiology . 1987;162:223–229
  55. Traipe E, Bilaniuk L, Shera D, Hurh P, Haselgrove J. Age-related changes in brain T1 values in children. Radiological Society of North America, presentation at Annual Meeting, 2000.
  56. Haselgrove J , Moore J , Wang Z , Traipe E , Bilaniuk L . A method for fast multislice T1 measurement (Feasibility studies on phantoms, young children, and children with Canavan’s disease) . J Magn Reson Imaging . 2000;11:360–367
  57. Kreis R , Ernst T , Ross BD . Development of the human brain (In vivo quantification of metabolite and water content with proton magnetic resonance spectroscopy) . Magn Reson Med . 1993;30:424–437
  58. Michaelis T , Merboldt KD , Bruhn H , Hanicke W , Frahm J . Absolute concentration of metabolites in the adult human brain in vivo (Quantification of localized proton MR spectra) . Radiology . 1993;187:219–227
  59. Provencher SW . Estimation of metabolite concentrations from localized in vivo proton NMR spectra . Magn Reson Med . 1993;30:672–679
  60. Bottomley PA . Spatial localization in NMR spectroscopy in vivo . Ann NY Acad Sci . 1987;508:333–348
  61. Laird NM , Ware JH . Random-effects models for longitudinal data . Biometrics . 1982;38:963–974
  62. Yildiz A , Moore CM , Sachs GS , et al.   Lithium-induced alterations in nucleoside triphosphate levels in human brain (A proton-decoupled 31P MRS study) . Psychiatry Res Neuroimag . 2005;138:51–59
  63. Banchaabouchi MA , Ortiz SP , Menendez R , Ren K , Maldonado-Vlaar CS . Chronic lithium decreases Nurr1 expression in the rat brain and impairs spatial discrimination . Pharmacol Biochem Behav . 2004;79:607–621

PII: S0887-8994(05)00257-2

doi: 10.1016/j.pediatrneurol.2005.04.015

Pediatric Neurology
Volume 33, Issue 4 , Pages 235-243 , October 2005

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