Neuroprotective effects of lithium: Implications for the treatment of Alzheimer's disease and related neurodegenerative disorders

ACS Chemical Neuroscience

Volumn 5, Issue 6, 2014, Pages 443-450

  Forlenza, O V ^a   De Paula, V J R ^a   Diniz, B S O ^b  

^a UNIVERSITY OF SÃO PAULO   (Brazil)

^b FEDERAL UNIVERSITY OF MINAS GERAIS   (Brazil)

Author keywords

Alzheimer's disease; amyotrophic lateral sclerosis; autophagy; bipolar disorder; GSK 3 ; Lithium; neuroprotection; Parkinson's disease

Indexed keywords

LITHIUM; LITHIUM DERIVATIVE; NEUROPROTECTIVE AGENT;

ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; BIPOLAR DISORDER; DEGENERATIVE DISEASE; DRUG EFFECT; HUMAN; NEUROBIOLOGY; NEUROPROTECTION; PRIORITY JOURNAL; REVIEW; ANIMAL; NEURODEGENERATIVE DISEASES; PATHOPHYSIOLOGY;

ALZHEIMER DISEASE; ANIMALS; HUMANS; LITHIUM COMPOUNDS; NEURODEGENERATIVE DISEASES; NEUROPROTECTIVE AGENTS;

EID: 84902688056     PISSN: None     EISSN: 19487193     Source Type: Journal    
DOI: 10.1021/cn5000309     Document Type: Review

References (114)

1. Cade, J. F. J. (1949) Lithium salts in the treatment of psychotic excitement Med. J. Aust. 36, 349-352
2. Nivoli, A. M., Colom, F., Murru, A., Pacchiarotti, I., Castro-Loli, P., and González-Pinto, A. 2011, New treatment guidelines for acute bipolar depression: a systematic review J. Affective Disord. 129 (1-3) 14-26
3. Diniz, B. S. and Teixeira, A. L. (2011) Brain-derived neurotrophic factor and Alzheimer's disease: physiopathology and beyond Neuromol. Med. 13 (4) 217-222
4. Pasquali, L., Busceti, C. L., Fulceri, F., Paparelli, A., and Fornai, F. (2010) Intracellular pathways underlying the effects of lithium Behav. Pharmacol. 21 (5-6) 473-492
5. Birch, N. J. (1974) Letter: lithium and magnesium-dependent enzymes Lancet 2, 965-966
6. 2+ competition for biomolecules Anal. Biochem. 272, 1-7
7. Grimes, C. A. and Jope, R. S. (2001) The multifaceted roles of glycogen synthase kinase 3β in cellular signaling Prog. Neurobiol. 65 (4) 391-426
8. Lee, F. H., Kaidanovich-Beilin, O., Roder, J. C., Woodgett, J. R., and Wong, A. H. (2011) Genetic inactivation of GSK3α rescues spine deficits in Disc1-L100P mutant mice Schizophr. Res. 129 (1) 74-79
9. Phiel, C. J., Wilson, C. A., Lee, V. M., and Klein, P. S. (2003) GSK-3α regulates production of Alzheimer's disease amyloid-β peptides Nature 423 (6938) 435-439
10. Hooper, C., Killick, R., and Lovestone, S. (2008) The GSK3 hypothesis of Alzheimer's disease J. Neurochem. 104 (6) 1433-1439
11. Forlenza, O. V., Diniz, B. S., Radanovic, M., Santos, F. S., Talib, L. L., and Gattaz, W. F. (2011) Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial Br J. Psychiatry 198 (5) 351-356
12. Klein, P. S. and Melton, D. A. (1996) A molecular mechanism for the effect of lithium on development Proc. Natl. Acad. Sci. U.S.A. 93 (16) 8455-8459
13. Ryves, W. J. and Harwood, A. J. (2001) Lithium inhibits glycogen synthase kinase-3 by competition for magnesium Biochem. Biophys. Res. Commun. 280, 720-725
14. Chalecka-Franaszek, E. and Chuang, D. M. (1999) Lithium activates the serine/threonine kinase Akt-1 and suppresses glutamate-induced inhibition of Akt-1 activity in neurons Proc. Natl. Acad. Sci. U.S.A. 96 (15) 8745-8750
15. O'Brien, W. T., Huang, J., Buccafusca, R., Garskof, J., Valvezan, A. J., Berry, G. T., and Klein, P. S. (2011) Glycogen synthase kinase-3 is essential for β-arrestin-2 complex formation and lithium-sensitive behaviors in mice J. Clin. Invest. 121 (9) 3756-3762
16. Pan, J. Q., Lewis, M. C., Ketterman, J. K., Clore, E. L., Riley, M., Richards, K. R., Berry-Scott, E., Liu, X., Wagner, F. F., Holson, E. B., Neve, R. L., Biechele, T. L., Moon, R. T., Scolnick, E. M., Petryshen, T. L., and Haggarty, S. J. (2011) AKT kinase activity is required for lithium to modulate mood-related behaviors in mice Neuropsychopharmacology 36 (7) 1397-1411
17. Mendes, C. T., Mury, F. B., de Sá Moreira, E., Alberto, F. L., Forlenza, O. V., Dias-Neto, E., and Gattaz, W. F. (2009) Lithium reduces Gsk3b mRNA levels: implications for Alzheimer Disease Eur. Arch. Psychiatry Clin. Neurosci. 259 (1) 16-22
18. Patel, S., Yenush, L., Rodríguez, P. L., Serrano, R., and Blundell, T. L. (2002) Crystal structure of an enzyme displaying both inositol-polyphosphate-1-phosphatase and 3′-phosphoadenosine-5′- phosphate phosphatase activities: a novel target of lithium therapy J. Mol. Biol. 315 (4) 677-685
19. Garcia-Arencibia, M., Hochfeld, W., Toh, P., and Rubinsztein, D. C. (2010) Autophagy, a guardian against neurodegeneration Semin. Cell Dev. Biol. 7, 691-698
20. Sarkar, S., Floto, R. A., Berger, Z., Imarisio, S., Cordenier, A., Pasco, M., Cook, L. J., and Rubinsztein, D. C. (2005) Lithium induces autophagy by inhibiting inositol monophosphatase J. Cell Biol. 170 (7) 1101-1111
21. Sarkar, S., Perlstein, E. O., Imarisio, S., Pineau, S., Cordenier, A., Maglathlin, R. L., Webster, J. A., Lewis, T. A., O'Kane, C. J., Schreiber, S. L., and Rubinsztein, D. C. (2007) Small molecules enhance autophagy and reduce toxicity in Huntington's disease models Nat. Chem. Biol. 3 (6) 331-338
22. Chiu, C. T. and Chuang, D. M. (2010) Molecular actions and therapeutic potential of lithium in preclinical and clinical studies of CNS disorders Pharmacol. Ther. 128 (2) 281-304
23. Kang, H. J., Noh, J. S., Bae, Y. S., and Gwag, B. J. (2003) Calcium-dependent prevention of neuronal apoptosis by lithium ion: essential role of phosphoinositide 3-kinase and phospholipase Cγ Mol. Pharmacol. 64, 228-234
24. Sasaki, T., Han, F., Shioda, N., Moriguchi, S., Kasahara, J., Ishiguro, K., and Fukunaga, K. (2006) Lithium-induced activation of Akt and CaM kinase II contributes to its neuroprotective action in a rat microsphere embolism model Brain Res. 1108, 98-106
25. Hooper, C., Killick, R., and Lovestone, S. (2008) The GSK3 hypothesis of Alzheimer's disease J. Neurochem. 104 (6) 1433-1439
26. Lovestone, S., Davis, D. R., Webster, M. T., Kaech, S., Brion, J. P., Matus, and Anderton, B. H. (1999) Lithium reduces tau phosphorylation: effects in living cells and in neurons at therapeutic concentrations Biol. Psychiatry 45 (8) 995-1003
27. Takahashi, M., Yasutake, K., and Tomizawa, K. (1999) Lithium inhibits neurite growth and tau protein kinase I/glycogen synthase kinase-3β- dependent phosphorylation of juvenile tau in cultured hippocampal neurons J. Neurochem. 73 (5) 2073-2083
28. Fu, Z. Q., Yang, Y., Song, J., Jiang, Q., Lin, Z. C., Wang, Q., and Tian, Q. (2010) LiCl attenuates thapsigargin-induced tau hyperphosphorylation by inhibiting GSK-3β in vivo and in vitro J. Alzheimer's Dis. 21 (4) 1107-1117
29. Esselmann, H., Maler, J. M., Kunz, N., Otto, M., Paul, S., Lewczuk, P., Rüther, E., Kornhuber, J., and Wiltfang, J. (2004) Lithium decreases secretion of Aβ1-42 and C-truncated species Aβ1-37/38/39/40 in chicken telencephalic cultures but specifically increases intracellular Aβ1-38 Neurodegener. Dis. 1 (4-5) 236-241
30. Phiel, C. J., Wilson, C. A., Lee, V. M., and Klein, P. S. (2003) GSK-3alpha regulates production of Alzheimer's disease amyloid-β peptides Nature 423 (6938) 435-439
31. Wei, H., Leeds, P. R., Qian, Y., Wei, W., Chen, R., and Chuang, D. (2000) β-Amyloid peptide-induced death of PC 12 cells and cerebellar granule cell neurons is inhibited by long-term lithium treatment Eur. J. Pharmacol. 392 (3) 117-123
32. Engel, T., Goñi-Oliver, P., Lucas, J. J., Avila, J., and Hernández, F. (2006) Chronic lithium administration to FTDP-17 tau and GSK-3beta overexpressing mice prevents tau hyperphosphorylation and neurofibrillary tangle formation, but pre-formed neurofibrillary tangles do not revert J. Neurochem. 99 (6) 1445-1455
33. Leroy, K., Ando, K., Héraud, C., Yilmaz, Z., Authelet, M., Boeynaems, J. M., Buée, L., De Decker, R., and Brion, J. P. (2010) Lithium treatment arrests the development of neurofibrillary tangles in mutant tau transgenic mice with advanced neurofibrillary pathology J. Alzheimer's Dis 19 (2) 705-719
34. Noble, W., Planel, E., Zehr, C., Olm, V., Meyerson, J., Suleman, F., Gaynor, K., Wang, L., LaFrancois, J., Feinstein, B., Burns, M., Krishnamurthy, P., Wen, Y., Bhat, R., Lewis, J., Dickson, D., and Duff, K. (2005) Inhibition of glycogen synthase kinase-3 by lithium correlates with reduced tauopathy and degeneration in vivo Proc. Natl. Acad. Sci. U.S.A. 102 (19) 6990-6995
35. Rockenstein, E., Torrance, M., Adame, A., Mante, M., Bar-on, P., Rose, J. B., Crews, L., and Masliah, E. (2007) Neuroprotective effects of regulators of the glycogen synthase kinase-3β signaling pathway in a transgenic model of Alzheimer's disease are associated with reduced amyloid precursor protein phosphorylation J. Neurosci. 27 (8) 1981-1991
36. Su, Y., Ryder, J., Li, B., Wu, X., Fox, N., Solenberg, P., Brune, K., Paul, S., Zhou, Y., Liu, F., and N.i, B. (2004) Lithium, a common drug for bipolar disorder treatment, regulates amyloid-β precursor protein processing Biochemistry 43, 6899-6908
37. Yu, F., Zhang, Y., and Chuang, D. M. (2012) Lithium reduces BACE1 overexpression, β amyloid accumulation, and spatial learning deficits in mice with traumatic brain injury J. Neurotrauma 29 (13) 2342-2351
38. Zhang, X., Heng, X., Li, T., Li, L., Yang, D., Zhang, X., Du, Y., Doody, R. S., and Le, W. (2011) Long-term treatment with lithium alleviates memory deficits and reduces amyloid-β production in an aged Alzheimer's disease transgenic mouse model J. Alzheimer's Dis. 24 (4) 739-749
39. Fiorentini, A., Rosi, M. C., Grossi, C., Luccarini, I., and Casamenti, F. (2010) Lithium improves hippocampal neurogenesis, neuropathology and cognitive functions in APP mutant mice PLoS One 5 (12) e14382
40. Alvarez, G., Muñoz-Montaño, J. R., Satrústegui, J., Avila, J., Bogónez, E., and Díaz-Nido, J. (1999) Lithium protects cultured neurons against β-amyloid-induced neurodegeneration FEBS Lett. 453 (3) 260-264
41. Alvarez, G., Muñoz-Montaño, J. R., Satrústegui, J., Avila, J., Bogónez, E., and Díaz-Nido, J. (2002) Regulation of tau phosphorylation and protection against β-amyloid-induced neurodegeneration by lithium. Possible implications for Alzheimer's disease Bipolar Disord. 4 (3) 153-165
42. Chen, R. W. and Chuang, D. M. (1999) Long term lithium treatment suppresses p53 and Bax expression but increases Bcl-2 expression. A prominent role in neuroprotection against excitotoxicity J. Biol. Chem. 274 (10) 6039-6042
43. Chen, G., Zeng, W. Z., Yuan, P. X., Huang, L. D., Jiang, Y. M., Zhao, Z. H., and Manji, H. K. (1999) The mood-stabilizing agents lithium and valproate robustly increase the levels of the neuroprotective protein bcl-2 in the CNS J. Neurochem. 72 (2) 879-882
44. Hashimoto, R., Senatorov, V., Kanai, H., Leeds, P., and Chuang, D. M. (2003) Lithium stimulates progenitor proliferation in cultured brain neurons Neuroscience 117 (1) 55-61
45. Kim, J. S., Chang, M. Y., Yu, I. T., Kim, J. H., Lee, S. H., Lee, Y. S., and Son, H. (2004) Lithium selectively increases neuronal differentiation of hippocampal neural progenitor cells both in vitro and in vivo J. Neurochem. 89 (2) 324-336
46. Chen, C. L., Lin, C. F., Chiang, C. W., Jan, M. S., and Lin, Y. S. (2006) Lithium inhibits ceramide- and etoposide-induced protein phosphatase 2A methylation, Bcl-2 dephosphorylation, caspase-2 activation, and apoptosis Mol. Pharmacol. 70 (2) 510-517
47. Ghribi, O., Herman, M. M., Spaulding, N. K., and Savory, J. (2002) Lithium inhibits aluminum-induced apoptosis in rabbit hippocampus, by preventing cytochrome c translocation, Bcl-2 decrease, Bax elevation and caspase-3 activation J. Neurochem. 82 (1) 137-145
48. Chou, C. H., Chou, A. K., Lin, C. C., Chen, W. J., Wei, C. C., Yang, M. C., Hsu, C. M., Lung, F. W., Loh, J. K., Howng, S. L., and Hong, Y. R. (2012) GSK3β regulates Bcl2L12 and Bcl2L12A anti-apoptosis signaling in glioblastoma and is inhibited by LiCl Cell Cycle 11 (3) 532-542
49. Shalbuyeva, N., Brustovetsky, T., and Brustovetsky, N. (2007) Lithium desensitizes brain mitochondria to calcium, antagonizes permeability transition, and diminishes cytochrome C release J. Biol. Chem. 282 (25) 18057-18068
50. Bachmann, R. F., Wang, Y., Yuan, P., Zhou, R., Li, X., Alesci, S., Du, J., and Manji, H. K. (2009) Common effects of lithium and valproate on mitochondrial functions: protection against methamphetamine-induced mitochondrial damage Int. J. Neuropsychopharmacol. 12 (6) 805-822
51. Quiroz, J. A., Machado-Vieira, R., Zarate, C. A., Jr., and Manji, H. K. (2010) Novel insights into lithium's mechanism of action: neurotrophic and neuroprotective effects Neuropsychobiology 62 (1) 50-60
52. Bosche, B., Schäfer, M., Graf, R., Härtel, F. V., Schäfer, U., and Noll, T. (2013) Lithium prevents early cytosolic calcium increase and secondary injurious calcium overload in glycolytically inhibited endothelial cells Biochem. Biophys. Res. Commun. 434 (2) 268-272
53. Ngok-Ngam, P., Watcharasit, P., Thiantanawat, A., and Satayavivad, J. (2013) Pharmacological inhibition of GSK3 attenuates DNA damage-induced apoptosis via reduction of p53 mitochondrial translocation and Bax oligomerization in neuroblastoma SH-SY5Y cells Cell Mol. Biol. Lett. 18 (1) 58-74
54. Feier, G., Valvassori, S. S., Varela, R. B., Resende, W. R., Bavaresco, D. V., Morais, M. O., Scaini, G., Andersen, M. L., Streck, E. L., and Quevedo, J. (2013) Lithium and valproate modulate energy metabolism in an animal model of mania induced by methamphetamine Pharmacol., Biochem. Behav. 103 (3) 589-596
55. Li, Q., Li, H., Roughton, K., Wang, X., Kroemer, G., Blomgren, K., and Zhu, C. (2010) Lithium reduces apoptosis and autophagy after neonatal hypoxia-ischemia Cell Death Dis. 1, e56
56. Chang, J. W., Choi, H., Cotman, S. L., and Jung, Y. K. (2011) Lithium rescues the impaired autophagy process in CbCln3(Δex7/8/Δex7/8) cerebellar cells and reduces neuronal vulnerability to cell death via IMPase inhibition J. Neurochem 116 (4) 659-668
57. Nahman, S., Belmaker, R. H., and Azab, A. N. (2012) Effects of lithium on lipopolysaccharide-induced inflammation in rat primary glia cells Innate Immun. 18 (3) 447458
58. Li, H., Li, Q., Du, X., Sun, Y., Wang, X., Kroemer, G., Blomgren, K., and Zhu, C. (2011) Lithium-mediated long-term neuroprotection in neonatal rat hypoxia-ischemia is associated with antiinflammatory effects and enhanced proliferation and survival of neural stem/progenitor cells J. Cereb. Blood Flow Metab. 10) 2106-2115
59. Basselin, M., Villacreses, N. E., Lee, H. J., Bell, J. M., and Rapoport, S. I. (2007) Chronic lithium administration attenuates up-regulated brain arachidonic acid metabolism in a rat model of neuroinflammation J. Neurochem. 102 (3) 761-772
60. Schwartz, M., Kipnis, J., Rivest, S., and Prat, A. (2013) How do immune cells support and shape the brain in health, disease, and aging? J. Neurosci. 33 (45) 17587-17596
61. Nivoli, A. M., Colom, F., Murru, A., Pacchiarotti, I., Castro-Loli, P., and González-Pinto, A. (2011) New treatment guidelines for acute bipolar depression: a systematic review J. Affective Disord. 129 (1-3) 14-26
62. Petronis, A. (2010) Epigenetics as a unifying principle in the aetiology of complex traits and diseases. Nature Jun 10 465 (7299) 721-7
63. Sugawara, H., Iwamoto, K., Bundo, M., Ueda, J., Miyauchi, T., Komori, A., Kazuno, A., Adati, N., Kusumi, I., Okazaki, Y., Ishigooka, J., Kojima, T., and Kato, T. (2011) Hypermethylation of serotonin transporter gene in bipolar disorder detected by epigenome analysis of discordant monozygotic twins Transl. Psychiatry 1, e25
64. Rao, J. S., Keleshian, V. L., Klein, S., and Rapoport, S. I. (2012) Epigenetic modifications in frontal cortex from Alzheimer's disease and bipolar disorder patients Transl. Psychiatry 2, e132
65. Sabunciyan, S., Aryee, M. J., Irizarry, R. A., Rongione, M., Webster, M. J., Kaufman, W. E., Murakami, P., Lessard, A., Yolken, R. H., Feinberg, A. P., and Potash, J. B. (2012) Genome-wide DNA methylation scan in major depressive disorder PLoS One 7, 34451
66. Rao, J. S., Keleshian, V. L., Klein, S., and Rapoport, S. I. (2012) Epigenetic modifications in frontal cortex from Alzheimer's disease and bipolar disorder patients Transl. Psychiatry 2, e132
67. Popkie, A. P., Zeidner, L. C., Albrecht, A. M., D'Ippolito, A., Eckardt, S., Newsom, D. E., Groden, J., Doble, B. W., Aronow, B., McLaughlin, K. J., White, P., and Phiel, C. J. (2010) Phosphatidylinositol 3-kinase (PI3K) signaling via glycogen synthase kinase-3 (Gsk-3) regulates DNA methylation of imprinted loci J. Biol. Chem. 285 (53) 41337-41347
68. Kessing, L. V., Søndergård, L., Forman, J. L., and Andersen, P.K. (2008) Lithium treatment and risk of dementia Arch. Gen. Psychiatry. 65 (11) 1331-1335
69. Kessing, L. V., Forman, J. L., and Andersen, P. K. (2010) Does lithium protect against dementia? Bipolar Disord. 12 (1) 87-94
70. Terao, T., Nakano, H., Inoue, Y., Okamoto, T., Nakamura, J., and Iwata, N. (2006) Lithium and dementia: a preliminary study Prog. Neuropsychopharmacol. Biol. Psychiatry 30 (6) 1125-1128
71. Nunes, P. V., Forlenza, O. V., and Gattaz, W. F. (2007) Lithium and risk for Alzheimer's disease in elderly patients with bipolar disorder Br. J. Psychiatry. 190, 359-360
72. Nitrini, R., Caramelli, P., Herrera, E., Jr., Bahia, V. S., Caixeta, L. F., Radanovic, M., Anghinah, R., Charchat-Fichman, H., Porto, C. S., Carthery, M. T., Hartmann, A. P., Huang, N., Smid, J., Lima, E. P., Takada, L. T., and Takahashi, D. Y. (2004) Incidence of dementia in a community-dwelling Brazilian population Alzheimer Dis. Assoc. Disord. 18 (4) 241-246
73. Rybakowski, J. K. and Suwalska, A. (2010) Excellent lithium responders have normal cognitive functions and plasma BDNF levels Int. J. Neuropsychopharmacol. 13 (5) 617-622
74. Machado-Vieira, R., Manji, H. K., and Zarate, C. A., Jr. (2009) The role of lithium in the treatment of bipolar disorder: convergent evidence for neurotrophic effects as a unifying hypothesis Bipolar Disord. 11 (2) 92-109
75. de Sousa, R. T., van de Bilt, M. T., Diniz, B. S., Ladeira, R. B., Portela, L. V., Souza, D. O., Forlenza, O. V., Gattaz, W. F., and Machado-Vieira, R. (2011) Lithium increases plasma brain-derived neurotrophic factor in acute bipolar mania: a preliminary 4-week study Neurosci. Lett. 494 (1) 54-56
76. Suwalska, A., Sobieska, M., and Rybakowski, J. K. (2010) Serum brain-derived neurotrophic factor in euthymic bipolar patients on prophylactic lithium therapy Neuropsychobiology 62 (4) 229-234
77. Machado-Vieira, R. and Manji, H. K. (2007) The role of lithium in the treatment of bipolar disorder: convergent evidence for neurotrophic effects as a unifying hypothesis Bipolar Disord. 11 (2) 92-109
78. Khairova, R., Pawar, R., Salvadore, G., Juruena, M. F., de Sousa, R. T., Soeiro-de-Souza, M. G., Salvador, M., Zarate, C. A., Gattaz, W. F., and Machado-Vieira, R. (2012) Effects of lithium on oxidative stress parameters in healthy subjects Mol. Med. Rep. 5 (3) 680-682
79. de Sousa, R. T., Zarate, C. A., Jr.., Zanetti, M. V., Costa, A. C., Talib, L. L., Gattaz, W. F., and Machado-Vieira, R. (2014) Oxidative stress in early stage Bipolar Disorder and the association with response to lithium J. Psychiatr. Res. 50, 36-41
80. Guloksuz, S., Altinbas, K., Aktas, C. E., Kenis, G., Bilgic, Gazioglu, S., Deniz, G., Oral, E. T., and van Os, J. (2012) Evidence for an association between tumor necrosis factor-alpha levels and lithium response J. Affective Disord. 143 (1-3) 148-152
81. Knijff, E. M., Breunis, M. N., Kupka, R. W., de Wit, H. J., Ruwhof, C., Akkerhuis, G. W., Nolen, W. A., and Drexhage, H. A. (2007) An imbalance in the production of IL-1β and IL-6 by monocytes of bipolar patients: restoration by lithium treatment Bipolar Disord. 9 (7) 743-753
82. Bearden, C. E., Thompson, P. M., Dalwani, M., Hayashi, K. M., Lee, A. D., Nicoletti, M., Trakhtenbroit, M., Glahn, D. C., Brambilla, P., Sassi, R. B., Mallinger, A. G., Frank, E., Kupfer, D. J., and Soares, J. C. (2007) Greater cortical gray matter density in lithium-treated patients with bipolar disorder Biol. Psychiatry 62 (1) 7-16
83. Moore, G. J., Cortese, B. M., Glitz, D. A., Zajac-Benitez, C., Quiroz, J. A., Uhde, T. W., Drevets, W. C., and Manji, H. K. (2009) A longitudinal study of the effects of lithium treatment on prefrontal and subgenual prefrontal gray matter volume in treatment-responsive bipolar disorder patients J. Clin. Psychiatry 70 (5) 699-705
84. Lyoo, I. K., Dager, S. R., Kim, J. E., Yoon, S. J., Friedman, S. D., Dunner, D. L., and Renshaw, P. F. (2010) Lithium-induced gray matter volume increase as a neural correlate of treatment response in bipolar disorder: a longitudinal brain imaging study Neuropsychopharmacology 35 (8) 1743-1750
85. van Erp, T. G., Thompson, P. M., Kieseppä, T., Bearden, C. E., Marino, A. C., Hoftman, G. D., Haukka, J., Partonen, T., Huttunen, M., Kaprio, J., Lönnqvist, J., Poutanen, V. P., Toga, A. W., and Cannon, T. D. (2012) Hippocampal morphology in lithium and non-lithium-treated bipolar I disorder patients, non-bipolar co-twins, and control twins Hum. Brain Mapp. 33 (3) 501-510
86. Hajek, T., Calkin, C., Blagdon, R., Slaney, C., and Alda, M. (2013) Type 2 Diabetes Mellitus: A Potentially Modifiable Risk Factor for Neurochemical Brain Changes in Bipolar Disorders Biol. Psychiatry 10.1016/j.biopsych.2013.11. 007
87. Forester, B. P., Finn, C. T., Berlow, Y. A., Wardrop, M., Renshaw, P. F., and Moore, C. M. (2008) Brain lithium, N-acetyl aspartate and myo-inositol levels in older adults with bipolar disorder treated with lithium: a lithium-7 and proton magnetic resonance spectroscopy study Bipolar Disord. 10 (6) 691-700
88. Silverstone, P. H., Wu, R. H., O'Donnell, T., Ulrich, M., Asghar, S. J., and Hanstock, C. C. (2003) Chronic treatment with lithium, but not sodium valproate, increases cortical N-acetyl-aspartate concentrations in euthymic bipolar patients Int. Clin. Psychopharmacol. 18 (2) 73-79
89. Macdonald, A., Briggs, K., Poppe, M., Higgins, A., Velayudhan, L., and Lovestone, S. (2008) A feasibility and tolerability study of lithium in Alzheimer's disease Int. J. Geriatr. Psychiatry 23 (7) 704-711
90. Hampel, H., Ewers, M., Bürger, K., Annas, P., Mörtberg, A., Bogstedt, A., Frölich, L., Schröder, J., Schönknecht, P., Riepe, M. W., Kraft, I., Gasser, T., Leyhe, T., Möller, H. J., Kurz, A., and Basun, H. (2009) Lithium trial in Alzheimer's disease: a randomized, single-blind, placebo-controlled, multicenter 10-week study J. Clin. Psychiatry 70 (6) 922-931
91. Leyhe, T., Eschweiler, G. W., Stransky, E., Gasser, T., Annas, P., Basun, H., and Laske, C. (2009) Increase of BDNF serum concentration in lithium treated patients with early Alzheimer's disease J. Alzheimer's Dis. 16 (3) 649-656
92. Straten, G., Saur, R., Laske, C., Gasser, T., Annas, P., Basun, H., and Leyhe, T. (2011) Influence of lithium treatment on GDNF serum and CSF concentrations in patients with early Alzheimer's disease Curr. Alzheimer Res. 8 (8) 853-859
93. Yang, J., Takahashi, Y., Cheng, E., Liu, J., Terranova, P. F., Zhao, B., Thrasher, J. B., Wang, H. G., and Li, B. (2010) GSK-3beta promotes cell survival by modulating Bif-1-dependent autophagy and cell death J. Cell Sci. 123 (6) 861-870
94. Gordon, P. H. (2011) Amyotrophic lateral sclerosis: pathophysiology, diagnosis and management CNS Drugs 25 (1) 1-15
95. Dill, J., Wang, H., Zhou, F., and Li, S. (2008) Inactivation of glycogen synthase kinase 3 promotes axonal growth and recovery in the CNS J. Neurosci. 28, 8914-8928
96. Busceti, C. L., Biagioni, F., Riozzi, B., Battaglia, G., Storto, M., Cinque, C., Molinaro, G., Gradini, R., Caricasole, A., Canudas, A. M., Bruno, V., Nicoletti, F., and Fornai, F. (2008) Enhanced tau phosphorylation in the hippocampus of mice treated with 3,4-methylenedioxymethamphetamine ("Ecstasy") J. Neurosci. 28, 3234-3245
97. Strong, M. J. (2008) The syndromes of frontotemporal dysfunction in amyotrophic lateral sclerosis Amyotrophic Lateral Scler. 9, 323-338
98. Fornai, F., Longone, P., Cafaro, L., Kastsiuchenka, O., Ferrucci, M., Manca, M. L., Lazzeri, G., Spalloni, A., Bellio, N., Lenzi, P., Modugno, N., Siciliano, G., Isidoro, C., Murri, L., Ruggieri, S., and Paparelli, A. (2008) Lithium delays progression of amyotrophic lateral sclerosis Proc. Natl. Acad. Sci. U.S.A. 105 (6) 2052-2057
99. Feng, H. L., Leng, Y., Ma, C. H., Zhang, J., Ren, M., and Chuang, D. M. (2008) Combined lithium and valproate treatment delays disease onset, reduces neurological deficits and prolongs survival in an amyotrophic lateral sclerosis mouse model Neuroscience 155 (3) 567-572
100. Chiò, A. and Mora, G. (2013) The final chapter of the ALS lithium saga Lancet Neurol. 12 (4) 324-325
101. Morrison, K. E., Dhariwal, S., Hornabrook, R., Savage, L., Burn, D. J., Khoo, T. K., Kelly, J., Murphy, C. L., Al-Chalabi, A., Dougherty, A., Leigh, P. N., Wijesekera, L., Thornhill, M., Ellis, C. M., O'Hanlon, K., Panicker, J., Pate, L., Ray, P., Wyatt, L., Young, C. A., Copeland, L., Ealing, J., Hamdalla, H., Leroi, I., Murphy, C., O'Keeffe, F., Oughton, E., Partington, L., Paterson, P., Rog, D., Sathish, A., Sexton, D., Smith, J., Vanek, H., Dodds, S., Williams, T. L., Steen, I. N., Clarke, J., Eziefula, C., Howard, R., Orrell, R., Sidle, K., Sylvester, R., Barrett, W., Merritt, C., Talbot, K., Turner, M. R., Whatley, C., Williams, C., Williams, J., Cosby, C., Hanemann, C. O., Iman, I., Philips, C., Timings, L., Crawford, S. E., Hewamadduma, C., Hibberd, R., Hollinger, H., McDermott, C., Mils, G., Rafiq, M., Shaw, P. J., Taylor, A., Waines, E., Walsh, T., Addison-Jones, R., Birt, J., Hare, M., and Majid, T. (2013) Lithium in patients with amyotrophic lateral sclerosis (LiCALS): a phase 3 multicentre, randomised, double-blind, placebo-controlled trial Lancet Neurol. 12 (4) 339-345
102. Feng, H. L., Leng, Y., Ma, C. H., Zhang, J., Ren, M., and Chuang, D. M. (2008) Combined lithium and valproate treatment delays disease onset, reduces neurological deficits and prolongs survival in an amyotrophic lateral sclerosis mouse model Neuroscience 155 (3) 567-572
103. Chiu, C.T.1, Liu, G., Leeds, P., and Chuang, D. M. (2011) Combined treatment with the mood stabilizers lithium and valproate produces multiple beneficial effects in transgenic mouse models of Huntington's disease Neuropsychopharmacology 36 (12) 2406-2421
104. Yu, F.1, Wang, Z., Tanaka, M., Chiu, C. T., Leeds, P., Zhang, Y., and Chuang, D. M. (2013) Posttrauma cotreatment with lithium and valproate: reduction of lesion volume, attenuation of blood-brain barrier disruption, and improvement in motor coordination in mice with traumatic brain injury J. Neurosurg. 119 (3) 766-773
105. Chiò, A. and Mora, G. (2013) The final chapter of the ALS lithium saga Lancet Neurol. 12 (4) 324-325
106. Youdim, M. B. and Arraf, Z. (2004) Prevention of MPTP (N -methyl-4-phenyl-1,2,3,6-tetrahydropyridine) dopaminergic neurotoxicity in mice by chronic lithium: involvements of Bcl-2 and Bax Neuropharmacology 46 (8) 1130-1140
107. Yong, Y., Ding, H., Fan, Z., Luo, J., and Ke, Z. J. (2011) Lithium fails to protect dopaminergic neurons in the 6-OHDA model of Parkinson's disease Neurochem. Res. 36 (3) 367-374
108. Senatorov, V. V., Ren, M., Kanai, H., Wei, H., and Chuang, D. M. (2004) Short-term lithium treatment promotes neuronal survival and proliferation in rat striatum infused with quinolinic acid, an excitotoxic model of Huntington's disease Mol. Psychiatry 9 (4) 371-385
109. Wei, H., Qin, Z. H., Senatorov, V. V., Wei, W., Wang, Y., Qian, Y., and Chuang, D. M. (2001) Lithium suppresses excitotoxicity-induced striatal lesions in a rat model of Huntington's disease Neuroscience 106 (3) 603-612
110. Wood, N. I. and Morton, A. J. (2003) Chronic lithium chloride treatment has variable effects on motor behaviour and survival of mice transgenic for the Huntington's disease mutation Brain Res. Bull. 61 (4) 375-383
111. Xilouri, M., Vogiatzi, T., Vekrellis, K., and Stefanis, L. (2008) Alphasynuclein degradation by autophagic pathways: a potential key to Parkinson's disease pathogenesis Autophagy 4, 917-919
112. Chen, G., Bower, K. A., Ma, C., Fang, S., Thiele, C. J., and Luo, J. (2004) Glycogen synthase kinase 3β (GSK3β) mediates 6-hydroxydopamine-induced neuronal death FASEB J. 18, 1162-1164
113. Ge, X. H., Zhu, G. J., Geng, D. Q., Zhang, Z. J., and Liu, C. F. (2012) Erythropoietin attenuates 6-hydroxydopamine-induced apoptosis via glycogen synthase kinase 3β-mediated mitochondrial translocation of Bax in PC12 cells Neurol. Sci. 33 (6) 1249-1256
114. Wei, H., Qin, Z. H., Senatorov, V. V., Wei, W., Wang, Y., Qian, Y., and Chuang, D. M. (2001) Lithium suppresses excitotoxicity-induced striatal lesions in a rat model of Huntington's disease Neuroscience 106, 603-612