Research progress on the effect of lithium on hematopoietic stem cells and neural stem cells

doi:10.3877/cma.j.issn.2095-1221.2018.06.008

Abstract

Abstract:

Lithium has been used in modern psychiatry for more than 65 years, constituting a cornerstone of long-term treatment for bipolar disorder.A number of biological properties of lithium have been demonstrated, including its antiviral, blood and nervous system protective effects.The effects of lithium on hematopoiesis, mesenchymal, neural stem cells and induced pluripotent stem cells were reviewed. Since the 1970s, lithium's role in maintaining high levels of hematopoietic stem cells (HSCs) and growth factors has been reported. Lithium can improve homing ability, colony forming ability and self-renewal ability of hematopoietic stem cells. Studies on the effects of lithium on neurogenesis have shown that lithium can promote the proliferation of progenitor cells in the hippocampal dentate gyrus and lead to increased mitotic activity of schwann cells. Lithium has been proved to be associated with neuroprotection and neurotrophic effects, and its specific effects are reflected in its improvement of synaptic plasticity, promotion of cell survival and inhibition of apoptosis. In clinical studies, lithium ion therapy has been found to increase the components of gray matter in the brain, especially in the frontal lobe, hippocampus and amygdala. The effects of lithium on stem cells involve multiple mediators and signal pathways, among which the most important mediators and signal pathways are believed to be glycogen synthase kinase-3 (gsk-3) and Wnt/-catenin pathways. In addition, the regulation of cAMP, protein kinase B, phosphatidylinositol 3-kinase (pi3k) and inositol monophosphatase (IMP) levels are also closely related to the effects of lithium. Lithium is currently being used in clinical trials to treat bipolar disorder and reduce the risk of dementia, and has beneficial effects on neurodegenerative diseases. In addition, induced pluripotent stem cells obtained from patients with bipolar disorder have been widely used to study the pathogenesis and the mechanism of action of lithium.

Key words: Lithium, Hematopoietic stem cells, Neural stem cells, Induced pluripotent stem cell

Ning Luo, Dejun Zhong. Research progress on the effect of lithium on hematopoietic stem cells and neural stem cells[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2018, 08(06): 366-372.

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References 74

1	Cade JF. Lithium salts in the treatment of psychotic excitement[J]. Aust N Z J Psychiatry, 1999, 33(5):619-622.
2	Radomski JL, Fuyat HN, Nelson AA, et al. The toxic effects,excretion and distribution of Lithium chloride[J]. J Pharmacol Exp Ther, 1950, 100(4:1):429-440.
3	Ratajczak MZ, Suszyńska M. Quo Vadis medycyno regeneracyjna?: Quo Vadis Regenerative Medicine?[J]. Acta Hematol Pol, 2013, 44(3):161-170.
4	Kozłowska-Skrzypczak M, Komarnicki M. Hematopoietic stem cells and hematopoiesis[J]. Diagn Lab, 2008, 44:231-239.
5	da Silva Meirelles L, Caplan AI, Nardi NB. In search of the in vivo identity of mesenchymal stem cells[J]. Stem Cells, 2008, 26(9):2287-2299.
6	Kemperamann G, Adult neurogenesis[M]. New York: oxford university press, 2006 .
7	Mayfield D, Brown RG. The clinical laboratory and electroencephalographic effects of lithium[J]. J Psychiatric Res, 1966, 4(3):207-219.
8	Murphy DL, Goodwin FK, Bunney JW. Leukocytosis during Lithium treat-ment[J]. Am J Psychiatry, 1971, 127(11):1559-1561.
9	Ozdemir MA, Sofuoğlu S, Tanrikulu G, et al. Lithium-induced hematologic changes in patients with bipolar affective disorder[J]. Biol Psychiatry, 1994, 35(3):210-213.
10	Hammond WP, Dale DC. Lithium therapy of canine cyclic hematopoiesis[J]. Blood, 1980, 55(1):26-28.
11	Levitt L, Quesenberry P. The effect of Lithium on murine hematopoiesis in a liquid culture system[J]. N Engl J Med, 1980, 302(13):713-719.
12	Gallicchio VS, Chen MG. Modulation of murine pluripotential stem cell pro-liferation in vivo by Lithium carbonate[J]. Blood, 1980, 56(6):1150-1152.
13	Joyce RA. Sequential effects of Lithium on haematopoiesis[J]. Br J Haematol, 1984, 56(2):307-321.
14	Ballin A, Lehman D, Sirota P, et al. Increased number of peripheral blood CD34(+) cells in lithium-treated patients[J]. Br J Haematol, 1998, 100(1):219-221.
15	Huang J, Nguyen-Mccarty M, Hexner EO, et al. Maintenance of hematopoietic stem cells through regulation of Wnt and mTOR pathways[J]. Nat Med, 2012, 18(12):1778-1785.
16	Walasek MA, Bystrykh L, Van Den Boom VA, et al. The combination of valproic acid and Lithium delays hematopoietic stem/progenitor cell differentiation[J]. Blood, 2012, 119(13):3050-3059.
17	Petrini M, Vaglini M, Carulli G, et al. Effects of Lithium and Rubidium on the differentiation of mononuclear cells[J]. Int J Tissue React, 1986, 8(5):391-392.
18	Harker WG, Rothstein G, Clarkson D, et al. Enhancement of colony-stimulating activity production by Lithium[J]. Blood, 1977, 49(2):263-267.
19	Turner A, Allalunis M. Mononuclear cell production of colony-stimulating activity in humans taking oral lithium carbonate[J]. Blood, 1978, 52:234.
20	Gamba-Vitalo C, Gallicchio VS, Watts TD, et al. Lithium stimulated in vitro megakaryocytopoiesis[J]. Exp Hematol, 1983, 11(5):382-388.
21	Yoshino JE, Devries GH. Effect of Lithium on schwann cell proliferation stimulated by axolemma-and myelin-enriched fractions[J]. J Neurochem, 1987, 48(4):1270-1277.
22	Kim JS, Chang MY, Yu IT, et al. Lithium selectively increases neuronal differentiation of hippocampal neural progenitor cells both in vitro and in vivo[J]. J Neurochem, 2004, 89(2):324-336.
23	Son H, Yu IT, Hwang SJ, et al. Lithium enhances long-term potentiation independently of hippocampal neurogenesis in the rat dentate gyrus[J]. J Neurochem, 2003, 85(4):872-881.
24	Chen G, Rajkowska G, Du F, et al. Enhancement of hippocampal neurogenesis by Lithium[J]. J Neurochem, 2000, 75(4):1729-1734.
25	Li H, Li Q, Du X, et al. Lithium-mediated long-term neuroprotection in neonatal rat hypoxia-ischemia is associated with antiin-ﬂammatory effects and enhanced proliferation and survival of neural stem/progenitor cells[J]. J Cereb Blood Flow Metab, 2011, 31(10):2106-2115.
26	Kang K, Kim YJ, Kim YH, et al. Lithium pretreatment reduces brain injury after intracerebral hemorrhage in rats[J]. Neurol Res, 2012, 34(5):447-454.
27	Huo K, Sun Y, Li H, et al. Lithium reduced neural progenitor apoptosis in the hippocampus and ameliorated functional deficits after irradiation to the immature mouse brain[J]. Mol Cell Neurosci, 2012, 51(1/2):32-42.
28	O'Leary OF, O'Connor RM, Cryan JF. Lithium-induced effects on adult hippocampal neurogenesis are topographically segregated along the dorso-ventral axis of stressed mice[J]. Neuropharmacology, 2012, 62(1):247-255.
29	Kara N, Narayanan S, Belmaker RH, et al. Chronic lithium treatment enhances the number of quiescent neural progenitors but not the number of DCX-positive immature neurons[J]. Int J Neuropsychopharmacol, 2015, 18(7):pyv003.
30	Segi-Nishida E, Warner-Schmidt JL, Duman RS. Electroconvulsive seizure and VEGF increase the proliferation of neural stem-like cells in rat hippocampus[J]. Proc Natl Acad Sci U S A, 2008, 105(32):11352-11357.
31	Encinas JM, Vaahtokari A, Enikolopov G. Fluoxetine targets early progenitor cells in the adult brain[J]. Proc Natl Acad Sci U S A, 2006, 103(21):8233-8238.
32	Hill EJ, Nagel DA, O'Neil JD, et al. Effects of Lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development[J]. PLoS One, 2013, 8(3):e58822.
33	Hasgekar NN, Gokhale PP, Amin MK, et al. Lithium inhibits growth in a murine neural precursor cell line[J]. Cell Biol Int, 1996, 20(12):781-786.
34	Misiuta IE, Saporta S, Sanberg PR, et al. Influence of retinoic acid and Lithium on proliferation and dopaminergic potential of human NT2 cells[J]. J Neurosci Res, 2006, 83(4):668-679.
35	Yucel K, Taylor VH, Mckinnon MC, et al. Bilateral hippocampal volume increase in patients with bipolar disorder and short-term Lithium treatment[J]. Neuropsychopharmacology, 2008, 33(2):361-367.
36	Bearden CE, Thompson PM, Dutton RA, et al. Three-dimensional mapping of hippocampal anatomy in unmedicated and lithium-treated patients with bipolar disorder[J]. Neuropsychopharmacology, 2008, 33(1):1229-1238.
37	Lyoo IK, Dager SR, Kim JE, et al. Lithium-Induced gray matter volume increase as a neural correlate of treatment response in bipolar disorder: a longitudinal brain imaging study[J]. Neuropsychopharmacology, 2010, 35(8):1743-1750.
38	Hallahan B, Newell J, Soares JC, et al. Structural magnetic resonance imaging in bipolar disorder: an international collaborative MegaAnalysis of individual adult patient data[J]. Biol Psychiatry, 2011, 69(4):326-335.
39	Selek S, Nicoletti M, Zunta-Soares GB, et al. A longitudinal study of fronto-limbic brain structures in patients with bipolar I disorder during lithium treatment[J]. J Affect Disord, 2013, 150(2):629-33.
40	Hajek T, Bauer M, Simhandl C, et al. Neuroprotective effect of lithium on hippocampal volumes in bipolar disorder Independent of long-term treatment response[J]. Psychol Med, 2014, 44(3):507-517.
41	Quiroz JA, Machado-Vieira R, Zarate JC, et al. Novel insights into Lithium's mechanism of action:neurotrophic and neuroprotective effects[J]. Neuropsychobiology, 2010, 62(1):50-60.
42	Inal-Emiroglu FN, Karabay N, Resmi H, et al. Correlations between amygdala volumes and serum levels of BDNF and NGF as a neurobiological markerin adolescents with bipolar disorder[J]. J Affect Disord, 2015, 182:50-56.
43	Benedetti F, Poletti S, Radaelli D, et al. Lithium and GSK-3b promoter gene variants inﬂuence cortical gray matter volumes in bipolar disorder[J]. Psychopharmacology (Berl), 2015, 232(7):1325-1336.
44	Allagui MS, Nciri R, Rouhaud MF, et al. Long-term exposure to low lithium concentrations stimulates proliferation, modifies stress protein expression pattern and enhances resistance to oxidative stress in SH-SY5Y cells[J]. Neurochem Res, 2009, 34(3):453-462.
45	Kessing LV, Forman JL, Andersen PK. Does Lithium protect against dementia?[J]. Bipolar Disord, 2010, 12(1):87-94.
46	Gerhard T, Devanand DP, Huang CC, et al. Lithium treatment and risk for dementia in adults with bipolar disorder: population-based cohort study[J]. Br J Psychiatry, 2015, 207(1):46-51.
47	Nunes PV, Forlenza OV, Gattaz WF. Lithium and risk for Alzheimer's disease in elderly patients with bipolar disorder[J]. Br J Psychiatry, 2007, 190:359-360.
48	Sofola-Adesakin O, Castillo-Quan JI, Rallis C, et al. Lithium suppresses Aβ pathology by inhibiting translation in an adult Drosophila model of Alzheimer's disease[J]. Front Aging Neurosci, 2014, 6:190.
49	Senatorov VV, Ren M, Kanai H, et al. Short term Lithium treatment promotes neuronal survival and proliferation in rat striatum in-fused with quinolinic acid,an excitotoxic model of Huntington's disease[J]. Mol Psychiatry, 2004, 9(4):371-385.
50	Dong BT, Tu GJ, Han YX, et al. Lithium enhanced cell proliferation and differentiation of mesenchymal stem cells to neural cells in rat spinal cord[J]. Int J Clin Exp Pathol, 2015, 8(3):2473-2483.
51	Sugiyama T, Kohara H, Noda M, et al. Maintenance of the hematopoi-etic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches[J]. Immunity, 2006, 25(6):977-988.
52	Kast RE. How Lithium treatment generates neutrophilia by enhancing phos-phorylation of GSK-3, increasing HIF-1 levels and how this path is important during engraftment[J]. Bone Marrow Transplant, 2008, 41(1):23-26.
53	Huang J, Zhang Y, Bersenev A, et al. Pivotal role for glycogen synthase kinase-3 in hematopoietic stem cell homeostasis in mice[J]. J Clin Invest, 2009, 119(12):3519-3529.
54	Hedgepeth C, Conrad LJ, Zhang J, et al. Activation of the Wnt signaling pathway:a molecular mechanism for Lithium action[J]. Dev Biol, 1997, 185(1):82-91.
55	Stambolic V, Ruel L, Woodgett JR. Lithium inhibits glycogen synthase kinase-3 activity and mimics Wingless signalling in intact cells[J]. Current Biology, 1996, 6(12):1664-1668.
56	Trowbridge JJ, Xenocostas A, Moon RT, et al. Glycogen synthase kinase-3 is an in vivo regulator of hematopoietic stem cell repopulation[J]. Nat Med, 2006, 12(1):89-98.
57	Ying QL, Wray J, Nichols J, et al. The ground state of embryonic stemb cell self-renewal[J]. Nature, 2008, 453(7194):519-523.
58	Doble BW, Patel S, Wood GA, et al. Functional redundancy of GSK-3alpha and GSK-3beta in Wnt/beta-catenin signaling shown by using an allelic series of embryonic stem cell lines[J]. Dev Cell, 2007, 12(6):957-971.
59	Miyoshi K, Kasahara K, Miyazaki I, et al. Lithium treatment elongates primary cilia in the mouse brain and in cultured cells[J]. Biochem Biophys Res Commun, 2009, 388(4):757-762.
60	Wexler EM, Geschwind DH, Palmer TD. Lithium regulates adult hippocampal progenitor development through canonical Wnt pathway activation[J]. Mol Psychiatry, 2008, 13(3):285-292.
61	Goessling W, North TE, Loewer S, et al. Genetic interaction of PGE2 and Wnt signaling regulates developmental specification of stem cells and regeneration[J]. Cell, 2009, 136(6):1136-1147.
62	Holmes T, O'brien TA, Knight R, et al. Glycogen synthase kinase-3 beta inhibition preserves hematopoietic stem cell activity and inhibits leukemic cell growth[J]. Stem Cells, 2008, 26(5):1288-1297.
63	Gallicchio VS. Lithium stimulation of in vitro granulopoiesis:evidence for mediation via Sodium transport pathways[J]. Br J Haematol, 1986, 62(3):455-466.
64	Inayat M, Gallicchio V. The effects of lithium on the immune system. In: Bauer M, Grof P, Muller-Oerlinghausen B, editors. Lithium in neuropsychiatry: the comprehensive guide[M]. Taylor & Francis, 2006, p.399-414.
65	Kleinerman ES, Knowles RD, Blick MB, et al. Lithium chloride stimu-lates human monocytes to secrete tumor necrosis factor/cachectin[J]. J Leukoc Biol, 1989, 46(5):484-492.
66	Gallicchio VS, Chen MG, Watts TD. Specificity of Lithium(Li+)to enhance the production of colony stimulating factor(GM-CSF)from mitogen-stimulated lymphocytes in vitro[J]. Cell Immunol, 1984, 85(1):58-66.
67	Doukas M, Shadduck RK, Waheed A, et al. Lithium stimulation of diffusion chamber colony growth is mediated by factors other than colony-stimulating factor[J]. Int J Cell Cloning, 1989, 7(3):168-178.
68	Chen HM, Delong CJ, Bame M, et al. Transcripts involved in Calcium signaling and telencephalic neuronal fate are altered in induced pluripotent stem cells from bipolar disorder patients[J]. Transl Psychiatry, 2014, 4:e375.
69	Wang JL, Shamah SM, Sun AX, et al. Label-free, live optical imaging of reprogrammed bipolar disorder patient-derived cells reveals a functional correlate of lithium responsiveness[J]. Transl Psychiatry, 2014, 4:e428.
70	Madison JM, Zhou F, Nigam A, et al. Charac-terization of bipolar disorder patient-specific induced pluripotent stem cells from a family reveals neurodevelopmental and mRNA expression abnormalities[J]. Mol Psychiatry, 2015, 20(6):703-717.
71	Viswanath B, Jose SP, Squassina A, et al. Cellular models to study bipolar disorder: A systematic review[J]. J Affect Disord, 2015, 184(1):36-50.
72	Oruch R, Elderbi MA, Khattab HA, et al. Lithium: a review of pharmacology, clinical uses, and toxicity[J]. Eur J Pharmacol, 2014, 740(5):464-473.
73	Adityanjee, Munshi KR, Thampy A. The syndrome of irreversible lithiumeffectuated neurotoxicity[J]. Clin Neuropharmacol, 2005, 28(1): 38-49.
74	Rybakowski JK. Lithium in neuropsychiatry: a 2010 update[J]. World J Biol Psychiatry, 2011, 12(5):340-348.

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