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01.12.2014 | Original Paper

Lithium Chloride Therapy Fails to Improve Motor Function in a Transgenic Mouse Model of Machado-Joseph Disease

verfasst von: Sara Duarte-Silva, Andreia Neves-Carvalho, Carina Soares-Cunha, Andreia Teixeira-Castro, Pedro Oliveira, Anabela Silva-Fernandes, Patrícia Maciel

Erschienen in: The Cerebellum | Ausgabe 6/2014

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Abstract

The accumulation of misfolded proteins in neurons, leading to the formation of cytoplasmic and nuclear aggregates, is a common theme in age-related neurodegenerative diseases, possibly due to disturbances of the proteostasis and insufficient activity of cellular protein clearance pathways. Lithium is a well-known autophagy inducer that exerts neuroprotective effects in different conditions and has been proposed as a promising therapeutic agent for several neurodegenerative diseases. We tested the efficacy of chronic lithium (10.4 mg/kg) treatment in a transgenic mouse model of Machado-Joseph disease, an inherited neurodegenerative disease, caused by an expansion of a polyglutamine tract within the protein ataxin-3. A battery of behavioral tests was used to assess disease progression. In spite of activating autophagy, as suggested by the increased levels of Beclin-1, Atg7, and LC3-II, and a reduction in the p62 protein levels, lithium administration showed no overall beneficial effects in this model concerning motor performance, showing a positive impact only in the reduction of tremors at 24 weeks of age. Our results do not support lithium chronic treatment as a promising strategy for the treatment of Machado-Joseph disease (MJD).

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Lin D, Mok H, Yatham LN. Polytherapy in bipolar disorder. CNS drugs. 2006;20(1):29–42.PubMedCrossRef

Goodwin FK. Rationale for using lithium in combination with other mood stabilizers in the management of bipolar disorder. J Clin Psychiatr. 2003;64 Suppl 5:18–24.

Gao XM, Fukamauchi F, Chuang DM. Long-term biphasic effects of lithium treatment on phospholipase C-coupled M3-muscarinic acetylcholine receptors in cultured cerebellar granule cells. Neurochem Int. 1993;22(4):395–403.PubMedCrossRef

Ozaki N, Chuang DM. Lithium increases transcription factor binding to AP-1 and cyclic AMP-responsive element in cultured neurons and rat brain. J Neurochem. 1997;69(6):2336–44.PubMedCrossRef

Klein PS, Melton DA. A molecular mechanism for the effect of lithium on development. Proc Natl Acad Sci U S A. 1996;93(16):8455–9.PubMedCentralPubMedCrossRef

Ryves WJ, Harwood AJ. Lithium inhibits glycogen synthase kinase-3 by competition for magnesium. Biochem Biophys Res Commun. 2001;280(3):720–5. doi:10.1006/bbrc.2000.4169.PubMedCrossRef

Hashimoto R, Takei N, Shimazu K, Christ L, Lu B, Chuang DM. Lithium induces brain-derived neurotrophic factor and activates TrkB in rodent cortical neurons: an essential step for neuroprotection against glutamate excitotoxicity. Neuropharmacology. 2002;43(7):1173–9.PubMedCrossRef

Fukumoto T, Morinobu S, Okamoto Y, Kagaya A, Yamawaki S. Chronic lithium treatment increases the expression of brain-derived neurotrophic factor in the rat brain. Psychopharmacol (Berl). 2001;158(1):100–6. doi:10.1007/s002130100871.CrossRef

Chen RW, Chuang DM. Long term lithium treatment suppresses p53 and Bax expression but increases Bcl-2 expression. A prominent role in neuroprotection against excitotoxicity. J Biol Chem. 1999;274(10):6039–42.PubMedCrossRef

10.

Hiroi T, Wei H, Hough C, Leeds P, Chuang DM. Protracted lithium treatment protects against the ER stress elicited by thapsigargin in rat PC12 cells: roles of intracellular calcium, GRP78 and Bcl-2. Pharmacogenomics J. 2005;5(2):102–11. doi:10.1038/sj.tpj.6500296.PubMedCrossRef

11.

Mattson MP, LaFerla FM, Chan SL, Leissring MA, Shepel PN, Geiger JD. Calcium signaling in the ER: its role in neuronal plasticity and neurodegenerative disorders. Trends Neurosci. 2000;23(5):222–9.PubMedCrossRef

12.

Bijur GN, De Sarno P, Jope RS. Glycogen synthase kinase-3beta facilitates staurosporine- and heat shock-induced apoptosis. Protection by lithium. J Biol Chem. 2000;275(11):7583–90.PubMedCrossRef

13.

Ren M, Senatorov VV, Chen RW, Chuang DM. Postinsult treatment with lithium reduces brain damage and facilitates neurological recovery in a rat ischemia/reperfusion model. Proc Natl Acad Sci U S A. 2003;100(10):6210–5. doi:10.1073/pnas.0937423100.PubMedCentralPubMedCrossRef

14.

Wei H, Leeds PR, Qian Y, Wei W, Chen R, Chuang D. Beta-amyloid peptide-induced death of PC 12 cells and cerebellar granule cell neurons is inhibited by long-term lithium treatment. Eur J Pharmacol. 2000;392(3):117–23.PubMedCrossRef

15.

Rohn TT, Vyas V, Hernandez-Estrada T, Nichol KE, Christie LA, Head E. Lack of pathology in a triple transgenic mouse model of Alzheimer’s disease after overexpression of the anti-apoptotic protein Bcl-2. J Neurosci. 2008;28(12):3051–9. doi:10.1523/JNEUROSCI.5620-07.2008.PubMedCrossRef

16.

Jacobsen JP, Mork A. The effect of escitalopram, desipramine, electroconvulsive seizures and lithium on brain-derived neurotrophic factor mRNA and protein expression in the rat brain and the correlation to 5-HT and 5-HIAA levels. Brain Res. 2004;1024(1–2):183–92. doi:10.1016/j.brainres.2004.07.065.PubMedCrossRef

17.

Berridge MJ, Downes CP, Hanley MR. Neural and developmental actions of lithium: a unifying hypothesis. Cell. 1989;59(3):411–9.PubMedCrossRef

18.

Quiroz JA, Gould TD, Manji HK. Molecular effects of lithium. Mol Interv. 2004;4(5):259–72. doi:10.1124/mi.4.5.6.PubMedCrossRef

19.

Phiel CJ, Klein PS. Molecular targets of lithium action. Annu Rev Pharmacol Toxicol. 2001;41:789–813. doi:10.1146/annurev.pharmtox.41.1.789.PubMedCrossRef

20.

Sarkar S, Floto RA, Berger Z, Imarisio S, Cordenier A, Pasco M, et al. Lithium induces autophagy by inhibiting inositol monophosphatase. J Cell Biol. 2005;170(7):1101–11. doi:10.1083/jcb.200504035.PubMedCentralPubMedCrossRef

21.

Sarkar S, Rubinsztein DC. Inositol and IP3 levels regulate autophagy: biology and therapeutic speculations. Autophagy. 2006;2(2):132–4.PubMedCrossRef

22.

Melendez A, Hall DH, Hansen M. Monitoring the role of autophagy in C. elegans aging. Methods Enzymol. 2008;451:493–520. doi:10.1016/S0076-6879(08)03229-1.PubMedCrossRef

23.

Xu M, Zhang HL. Death and survival of neuronal and astrocytic cells in ischemic brain injury: a role of autophagy. Acta Pharmacol Sin. 2011;32(9):1089–99. doi:10.1038/aps.2011.50.PubMedCentralPubMedCrossRef

24.

Rubinsztein DC. Autophagy induction rescues toxicity mediated by proteasome inhibition. Neuron. 2007;54(6):854–6. doi:10.1016/j.neuron.2007.06.005.PubMedCrossRef

25.

Rubinsztein DC, Gestwicki JE, Murphy LO, Klionsky DJ. Potential therapeutic applications of autophagy. Nat Rev Drug Discov. 2007;6(4):304–12. doi:10.1038/nrd2272.PubMedCrossRef

26.

Lee SJ, Lim HS, Masliah E, Lee HJ. Protein aggregate spreading in neurodegenerative diseases: problems and perspectives. Neurosci Res. 2011;70(4):339–48. doi:10.1016/j.neures.2011.05.008.PubMedCentralPubMedCrossRef

27.

Levine B, Kroemer G. Autophagy in the pathogenesis of disease. Cell. 2008;132(1):27–42. doi:10.1016/j.cell.2007.12.018.PubMedCentralPubMedCrossRef

28.

Cuervo AM, Stefanis L, Fredenburg R, Lansbury PT, Sulzer D. Impaired degradation of mutant alpha-synuclein by chaperone-mediated autophagy. Science. 2004;305(5688):1292–5. doi:10.1126/science.1101738.PubMedCrossRef

29.

Cuervo AM. Autophagy: in sickness and in health. Trends Cell Biol. 2004;14(2):70–7. doi:10.1016/j.tcb.2003.12.002.PubMedCrossRef

30.

Ravikumar B, Vacher C, Berger Z, Davies JE, Luo S, Oroz LG, et al. Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat Genet. 2004;36(6):585–95. doi:10.1038/ng1362.PubMedCrossRef

31.

Sarkar S, Ravikumar B, Floto RA, Rubinsztein DC. Rapamycin and mTOR-independent autophagy inducers ameliorate toxicity of polyglutamine-expanded huntingtin and related proteinopathies. Cell Death Differ. 2009;16(1):46–56. doi:10.1038/cdd.2008.110.PubMedCrossRef

32.

Ravikumar B, Duden R, Rubinsztein DC. Aggregate-prone proteins with polyglutamine and polyalanine expansions are degraded by autophagy. Hum Mol Genet. 2002;11(9):1107–17.PubMedCrossRef

33.

Nixon RA, Wegiel J, Kumar A, Yu WH, Peterhoff C, Cataldo A, et al. Extensive involvement of autophagy in Alzheimer disease: an immuno-electron microscopy study. J Neuropathol Exp Neurol. 2005;64(2):113–22.PubMed

34.

Webb JL, Ravikumar B, Atkins J, Skepper JN, Rubinsztein DC. Alpha-synuclein is degraded by both autophagy and the proteasome. J Biol Chem. 2003;278(27):25009–13. doi:10.1074/jbc.M300227200.PubMedCrossRef

35.

Berger Z, Ravikumar B, Menzies FM, Oroz LG, Underwood BR, Pangalos MN, et al. Rapamycin alleviates toxicity of different aggregate-prone proteins. Hum Mol Genet. 2006;15(3):433–42. doi:10.1093/hmg/ddi458.PubMedCrossRef

36.

Menzies FM, Huebener J, Renna M, Bonin M, Riess O, Rubinsztein DC. Autophagy induction reduces mutant ataxin-3 levels and toxicity in a mouse model of spinocerebellar ataxia type 3. Brain : J Neurol. 2010;133(Pt 1):93–104. doi:10.1093/brain/awp292.CrossRef

37.

Nascimento-Ferreira I, Santos-Ferreira T, Sousa-Ferreira L, Auregan G, Onofre I, Alves S et al. Overexpression of the autophagic beclin-1 protein clears mutant ataxin-3 and alleviates Machado-Joseph disease. Brain. 2011. doi:10.1093/brain/awr047.

38.

Meijer AJ, Codogno P. Regulation and role of autophagy in mammalian cells. Int J Biochem Cell Biol. 2004;36(12):2445–62. doi:10.1016/j.biocel.2004.02.002.PubMedCrossRef

39.

Yu WH, Cuervo AM, Kumar A, Peterhoff CM, Schmidt SD, Lee JH, et al. Macroautophagy—a novel beta-amyloid peptide-generating pathway activated in Alzheimer’s disease. J Cell Biol. 2005;171(1):87–98. doi:10.1083/jcb.200505082.PubMedCentralPubMedCrossRef

40.

Menzies FM, Ravikumar B, Rubinsztein DC. Protective roles for induction of autophagy in multiple proteinopathies. Autophagy. 2006;2(3):224–5.PubMedCrossRef

41.

Xiong N, Jia M, Chen C, Xiong J, Zhang Z, Huang J, et al. Potential autophagy enhancers attenuate rotenone-induced toxicity in SH-SY5Y. Neuroscience. 2011;199:292–302. doi:10.1016/j.neuroscience.2011.10.031.PubMedCrossRef

42.

Stambolic V, Ruel L, Woodgett JR. Lithium inhibits glycogen synthase kinase-3 activity and mimics wingless signalling in intact cells. Curr Biol. 1996;6(12):1664–8.PubMedCrossRef

43.

Feng HL, Leng Y, Ma CH, Zhang J, Ren M, Chuang DM. Combined lithium and valproate treatment delays disease onset, reduces neurological deficits and prolongs survival in an amyotrophic lateral sclerosis mouse model. Neuroscience. 2008;155(3):567–72. doi:10.1016/j.neuroscience.2008.06.040.PubMedCentralPubMedCrossRef

44.

Fornai F, Longone P, Cafaro L, Kastsiuchenka O, Ferrucci M, Manca ML et al. Lithium delays progression of amyotrophic lateral sclerosis. Proceedings of the National Academy of Sciences of the United States of America. 2008;105(6):2052-7. doi:10.1073/pnas.0708022105

45.

Wood NI, Morton AJ. Chronic lithium chloride treatment has variable effects on motor behaviour and survival of mice transgenic for the Huntington’s disease mutation. Brain Res Bull. 2003;61(4):375–83.PubMedCrossRef

46.

Watase K, Gatchel JR, Sun Y, Emamian E, Atkinson R, Richman R, et al. Lithium therapy improves neurological function and hippocampal dendritic arborization in a spinocerebellar ataxia type 1 mouse model. PLoS Med. 2007;4(5):e182. doi:10.1371/journal.pmed.0040182.PubMedCentralPubMedCrossRef

47.

Jia DD, Zhang L, Chen Z, Wang CR, Huang FZ, Duan RH et al. Lithium chloride alleviates neurodegeneration partly by inhibiting activity of GSK3beta in a SCA3 Drosophila model. Cerebellum. 2013. doi:10.1007/s12311-013-0498-3.

48.

Silva-Fernandes A, Duarte-Silva S, Neves-Carvalho A, Amorim M, Soares-Cunha C, Oliveira P et al. Chronic treatment with 17-DMAG improves balance and coordination in a new mouse model of Machado-Joseph disease. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics. 2014. doi:10.1007/s13311-013-0255-9.

49.

Nicklas W, Baneux P, Boot R, Decelle T, Deeny AA, Fumanelli M, et al. Recommendations for the health monitoring of rodent and rabbit colonies in breeding and experimental units. Lab Anim. 2002;36(1):20–42.PubMedCrossRef

50.

Silva-Fernandes A, Costa MD, Duarte-Silva S, Oliveira P, Botelho CM, Martins L et al. Motor uncoordination and neuropathology in a transgenic mouse model of Machado-Joseph disease lacking intranuclear inclusions and ataxin-3 cleavage products. Neurobiol Dis. 2010. doi:10.1016/j.nbd.2010.05.021.

51.

Rogers DC, Fisher EM, Brown SD, Peters J, Hunter AJ, Martin JE. Behavioral and functional analysis of mouse phenotype: SHIRPA, a proposed protocol for comprehensive phenotype assessment. Mamm Genome : Off J Int Mamm Genome Soc. 1997;8(10):711–3.CrossRef

52.

Carter RJ, Lione LA, Humby T, Mangiarini L, Mahal A, Bates GP, et al. Characterization of progressive motor deficits in mice transgenic for the human Huntington’s disease mutation. J Neurosci : Off J Soc Neurosci. 1999;19(8):3248–57.

53.

Rafael JA, Nitta Y, Peters J, Davies KE. Testing of SHIRPA, a mouse phenotypic assessment protocol, on Dmd(mdx) and Dmd(mdx3cv) dystrophin-deficient mice. Mamm Genome. 2000;11(9):725–8. doi:10.1007/s003350010149.PubMedCrossRef

54.

JH Z. Biostatistical analysis (4th Edition). Prentice Hall; 1999

55.

Klionsky DJ, Abeliovich H, Agostinis P, Agrawal DK, Aliev G, Askew DS, et al. Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy. 2008;4(2):151–75.PubMedCentralPubMedCrossRef

56.

Itakura E, Kishi C, Inoue K, Mizushima N. Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG. Mol Biol Cell. 2008;19(12):5360–72. doi:10.1091/mbc.E08-01-0080.PubMedCentralPubMedCrossRef

57.

Baptista T, Teneud L, Contreras Q, Alastre T, Burguera JL, de Burguera M, et al. Lithium and body weight gain. Pharmacopsychiatry. 1995;28(2):35–44. doi:10.1055/s-2007-979586.PubMedCrossRef

58.

Saute JAM, da Silva ACF, Souza GN, Russo AD, Donis KC, Vedolin L, et al. Body mass index is inversely correlated with the expanded CAG repeat length in SCA3/MJD patients. Cerebellum. 2012;11(3):771–4.PubMedCrossRef

59.

Lalonde R, Strazielle C. Brain regions and genes affecting limb-clasping responses. Brain Res Rev. 2011;67(1–2):252–9. doi:10.1016/j.brainresrev.2011.02.005.PubMedCrossRef

60.

Chou AH, Yeh TH, Ouyang P, Chen YL, Chen SY, Wang HL. Polyglutamine-expanded ataxin-3 causes cerebellar dysfunction of SCA3 transgenic mice by inducing transcriptional dysregulation. Neurobiol Dis. 2008;31(1):89–101. doi:10.1016/j.nbd.2008.03.011.PubMedCrossRef

61.

Cemal CK, Carroll CJ, Lawrence L, Lowrie MB, Ruddle P, Al-Mahdawi S, et al. YAC transgenic mice carrying pathological alleles of the MJD1 locus exhibit a mild and slowly progressive cerebellar deficit. Hum Mol Genet. 2002;11(9):1075–94.PubMedCrossRef

62.

Mangiarini L, Sathasivam K, Seller M, Cozens B, Harper A, Hetherington C, et al. Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell. 1996;87(3):493–506.PubMedCrossRef

63.

Fernagut PO, Diguet E, Bioulac B, Tison F. MPTP potentiates 3-nitropropionic acid-induced striatal damage in mice: reference to striatonigral degeneration. Exp Neurol. 2004;185(1):47–62.PubMedCrossRef

64.

Wirths O, Weis J, Kayed R, Saido TC, Bayer TA. Age-dependent axonal degeneration in an Alzheimer mouse model. Neurobiol Aging. 2007;28(11):1689–99. doi:10.1016/j.neurobiolaging.2006.07.021.PubMedCrossRef

65.

Lalonde R, Dumont M, Staufenbiel M, Strazielle C. Neurobehavioral characterization of APP23 transgenic mice with the SHIRPA primary screen. Behav Brain Res. 2005;157(1):91–8. doi:10.1016/j.bbr.2004.06.020.PubMedCrossRef

66.

Lalonde R, Lewis TL, Strazielle C, Kim H, Fukuchi K. Transgenic mice expressing the betaAPP695SWE mutation: effects on exploratory activity, anxiety, and motor coordination. Brain Res. 2003;977(1):38–45.PubMedCrossRef

67.

Brooks SP, Dunnett SB. Tests to assess motor phenotype in mice: a user’s guide. Nat Rev Neurosci. 2009;10(7):519–29. doi:10.1038/nrn2652.PubMedCrossRef

68.

Riess O, Rub U, Pastore A, Bauer P, Schols L. SCA3: neurological features, pathogenesis and animal models. Cerebellum. 2008;7(2):125–37. doi:10.1007/s12311-008-0013-4.PubMedCrossRef

69.

Costa MD, Paulson HL. Toward understanding Machado-Joseph disease. Prog Neurobiol. 2011. doi:10.1016/j.pneurobio.2011.11.006

70.

Matos CA, de Macedo-Ribeiro S, Carvalho AL. Polyglutamine diseases: the special case of ataxin-3 and Machado-Joseph disease. Prog Neurobiol. 2011;95(1):26–48. doi:10.1016/j.pneurobio.2011.06.007.PubMedCrossRef

71.

Xiao H, Tang J, Hu Z, Tan J, Tang B, Jiang Z. [Polyglutamine-expanded ataxin-3 is degraded by autophagy]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2010;27(1):23-8. doi:10.3760/cma.j.issn.1003-9406.2010.01.005.

72.

Paulson HL, Perez MK, Trottier Y, Trojanowski JQ, Subramony SH, Das SS, et al. Intranuclear inclusions of expanded polyglutamine protein in spinocerebellar ataxia type 3. Neuron. 1997;19(2):333–44.PubMedCrossRef

73.

Cheung ZH, Ip NY. Autophagy deregulation in neurodegenerative diseases—recent advances and future perspectives. J Neurochem. 2011;118(3):317–25. doi:10.1111/j.1471-4159.2011.07314.x.PubMedCrossRef

74.

Mizushima N, Levine B, Cuervo AM, Klionsky DJ. Autophagy fights disease through cellular self-digestion. Nature. 2008;451(7182):1069–75. doi:10.1038/nature06639.PubMedCentralPubMedCrossRef

75.

Goti D, Katzen SM, Mez J, Kurtis N, Kiluk J, Ben-Haiem L, et al. A mutant ataxin-3 putative-cleavage fragment in brains of Machado-Joseph disease patients and transgenic mice is cytotoxic above a critical concentration. J Neurosci : Off J Soc Neurosci. 2004;24(45):10266–79. doi:10.1523/JNEUROSCI.2734-04.2004.CrossRef

76.

Schmitt I, Brattig T, Gossen M, Riess O. Characterization of the rat spinocerebellar ataxia type 3 gene. Neurogenetics. 1997;1(2):103–12.PubMedCrossRef

77.

Sanberg PR, Fibiger HC, Mark RF. Body weight and dietary factors in Huntington’s disease patients compared with matched controls. Med J Aust. 1981;1(8):407–9.PubMed

78.

Gelenberg AJ, Jefferson JW. Lithium tremor. J Clin Psychiatry. 1995;56(7):283–7.PubMed

79.

Bettencourt C, Santos C, Coutinho P, Rizzu P, Vasconcelos J, Kay T, et al. Parkinsonian phenotype in Machado-Joseph disease (MJD/SCA3): a two-case report. BMC Neurol. 2011;11:131. doi:10.1186/1471-2377-11-131.PubMedCentralPubMedCrossRef

80.

Coutinho P, Sequeiros J. Clinical, genetic and pathological aspects of Machado-Joseph disease. J Genet Hum. 1981;29(3):203–9.PubMed

81.

Ishida C, Sakajiri K, Yoshikawa H, Sakashita Y, Okino S, Yamaguchi K, et al. Lower limb tremor in Machado-Joseph disease. Neurology. 1998;51(4):1225–6.PubMedCrossRef

82.

Nandagopal R, Moorthy SG. Dramatic levodopa responsiveness of dystonia in a sporadic case of spinocerebellar ataxia type 3. Postgrad Med J. 2004;80(944):363–5.PubMedCentralPubMedCrossRef

83.

Savvopoulos S, Golaz J, Bouras C, Constantinidis J, Tissot R. Huntington chorea. Anatomoclinical and genetic study of 17 cases. Encéphale. 1990;16(4):251–9.PubMed

84.

Miodownik C, Witztum E, Lerner V. Lithium-induced tremor treated with vitamin B6: a preliminary case series. Int J Psychiatry Med. 2002;32(1):103–8.PubMedCrossRef

85.

Tremont G, Stern RA. Minimizing the cognitive effects of lithium therapy and electroconvulsive therapy using thyroid hormone. Int J Neuropsychopharmacol. 2000;3(2):175–86. doi:10.1017/S1461145700001838.PubMedCrossRef

86.

Grignon S, Bruguerolle B. Cerebellar lithium toxicity: a review of recent literature and tentative pathophysiology. Therapie. 1996;51(2):101–6.PubMed

87.

Peiffer J. Clinical and neuropathological aspects of long-term damage to the central nervous system after lithium medication. Arch Psychiatr Nervenkr. 1981;231(1):41–60.PubMedCrossRef

88.

Niethammer M, Ford B. Permanent lithium-induced cerebellar toxicity: three cases and review of literature. Mov Disord. 2007;22(4):570–3. doi:10.1002/mds.21318.PubMedCrossRef

89.

Saute JA, Machado de Castilhos R, Monte TL, Schumacher-Schuh AF, Donis KC, D’Avila R et al. A randomized, phase 2 clinical trial of lithium carbonate in Machado-Joseph disease. Movement disorders : official journal of the Movement Disorder Society. 2014. doi:10.1002/mds.25803.

Titel: Lithium Chloride Therapy Fails to Improve Motor Function in a Transgenic Mouse Model of Machado-Joseph Disease
verfasst von: Sara Duarte-Silva
Andreia Neves-Carvalho
Carina Soares-Cunha
Andreia Teixeira-Castro
Pedro Oliveira
Anabela Silva-Fernandes
Patrícia Maciel
Publikationsdatum: 01.12.2014
Verlag: Springer US
Erschienen in: The Cerebellum / Ausgabe 6/2014
Print ISSN: 1473-4222
Elektronische ISSN: 1473-4230
DOI: https://doi.org/10.1007/s12311-014-0589-9

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