A systematic analysis of neurobiological roles of lithium

Close metadata

Recommended articles:

Russian experience in using a combination of fixed doses of donepezil and memantine in the treatment of Alzheimer’s disease as an observational non-interventional multicenter program. S.S. Korsakov Journal of Neurology and Psychiatry. 2023;(12):69-75

The impact of therapy with Mexidol on neurological deficit and functional outcome in patients with ischemic stroke: a systematic review and meta-analysis. S.S. Korsakov Journal of Neurology and Psychiatry. 2023;(12-2):49-60

Traumatic brain injury as risk factor of Alzheimer’s disease and possibilities of pathogenetic therapy. S.S. Korsakov Journal of Neurology and Psychiatry. 2024;(1):45-54

Glymphatic dysfunction and sleep disorders: indirect effects on Alzheimer’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2024;(4):7-12

Ginkgolide B: mechanisms of neurobiological effects, prospects for use in the therapy of Alzheimer’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2024;(4):22-27

Associations of serum neuromarkers with clinical features of Parkinson’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2024;(4):145-152

Comparative characteristics of neuropsychological and neurometabolic changes in patients with Alzheimer’s disease and vascular cognitive impairment. S.S. Korsakov Journal of Neurology and Psychiatry. 2024;(4-2):17-24

Impairment of attention and executive functions in chronic cerebrovascular disease and Alzheimer’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2024;(4-2):25-32

Assessment of the significance of dilated perivascular spaces and nocture arterial hypertension in the development of Alzheimer’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2024;(4-2):33-40

Features of lung damage in baclofen poisoning. Forensic Medical Expertise. 2024;(1):29-33

Lithium salts have been the mainstay of treatment for bipolar disorder for more than 50 years, since the FDA approved the treatment in 1970. Molecular mechanisms of lithium’s action include inhibition of glycogen synthase kinase 3 beta and inositol monophosphatase, resulting in induction of brain-derived neurotrophic factor, antiapoptotic proteins, deprivation of calcium-induced apoptosis. Recent findings suggest autophagy regulation as a possible mechanism of lithium neuroprotective action. Moreover, lithium treatment has been reported to decrease accumulation of various pathological proteins including phosphorylated tau and amyloid-B. Also, telomeres length and telomerase activity are suggested to be upregulated by lithium. Clinical applications of lithium treatment include various neurodegenerative diseases, primarily Alzheimer disease, with increasing importance given to the use of lithium microdoses. Chemoreactome screening is used to find more safe and effective lithium compounds.

Keywords:

lithium therapy

autophagy

telomerase

chemoinformatics

neurocytology

toxicology

neuroprotection

Alzheimer’s disease

Authors:

Gogoleva I.V.

Ivanovo State Medical Academy;
Russian Satellite Center of the Trace Elements Institute for UNESCO

Gromova O.A.

Federal Research Center «Computer Science and Control»

ORCID: 0000-0002-7663-710X

Torshin I.Yu.

Federal Research Center «Computer Science and Control»

ORCID: 0000-0002-2659-7998

Grishina T.R.

Ivanovo State Medical Academy of the Ministry of Health of Russia

Pronin A.V.

Ivanovo State Medical Academy;
Russian Satellite Center of the Trace Elements Institute for UNESCO

Received:

06.06.2022

Accepted:

11.07.2022

List of references:

Garrod AB. The nature and treatment of gout and rheumatic gout. The British and Foreign Medico-Chirurgical Review. 1860;5(50):419-435.
Hammond WA. A treatise on diseases of the nervous system. New York: Appleton; 1871. https://doi.org/10.1017/s0368315x00003650
Shorter E. The history of lithium therapy. Bipolar Disorders. 2009;11(2):4-9. https://doi.org/10.1111/j.1399-5618.2009.00706.x
Cade JF. Lithium salts in the treatment of psychotic excitement. Medical Journal of Australia. 1949;2(10):349-352. https://doi.org/10.1080/j.1440-1614.1999.06241.x
Noack CH, Trautner EM. The lithium treatment of maniacal psychosis. Medical Journal of Australia. 1951;2(7):219-222. https://doi.org/10.5694/j.1326-5377.1951.tb68249.x
Fyro B. Litarex (Dumex) — A new lithium preparation. Lakartidningen. 1975;72(51):5079.
Morrison JM, Pritchard HD, Braude MC, et al. Plasma and brain lithium levels after lithium carbonate and lithium chloride administration by different routes in rats. Proceedings of the Society for Experimental Biology and Medicine. 2016;137(3):889-892. https://doi.org/10.3181/00379727-137-35687
Olbrich R, Watzl H, Volter M, et al. Lithium in the treatment of chronic alcoholic patients with brain damage — A controlled study. Der Nervenarzt. 1991;62(3):182-186.
Dunderer M. Lithium aspartate in drug dependence. Fortschritte der Medizin. 1982;100(33):1500-1502.
Persson G. Comparison of plasma lithium levels and their interindividual variations with coated lithium carbonate tablets and a medium slow-release lithium sulphate preparation (Lithionit Duretter). Acta Psychiatrica Scandinavica. 1977;55(2):147-152. https://doi.org/10.1111/j.1600-0447.1977.tb00151.x
Lyubimov BI, Tolmacheva NS, Ostrovskaya RU. Experimental study of the neurotropic activity of lithium oxybutyrate. Farmakologiya i toksikologiya. 1980;(Vyp. 3):273-277. (In Russ.).
Shurygin AYa, Kravcov AA, Nemchinova EA, et al. Studying of the antioxidatic and neuroprotective properties of lithium salt of the comenic acid. Izv. vuzov. Sev.-Kavk. region. Estestv. Nauki. 2012;3:77-79. (In Russ.).
Smith AJ, Kim S-H, Tan J, et al. Plasma and brain pharmacokinetics of previously unexplored lithium salts. RSC Advances. 2014;4(24):12362-12365. https://doi.org/10.1039/C3RA46962J
Lippmann S, Evans R. A comparison of three types of lithium release preparations. Hospital & Community Psychiatry. 1983;34(2):113-114. https://doi.org/10.1176/ps.34.2.113
Chokhawala K, Lee S, Saadabadi A. Lithium. In StatPearls Internet. StatPearls Publishing. 2020.
Couffignal C, Chevillard L, Balkhi S, et al. The pharmacokinetics of lithium. In: The science and practice of lithium therapy. Springer. 2016. https://doi.org/10.1007/978-3-319-45923-3_2
Nieper H-A. Recalcification of bone metastases by calcium diorotate. Agressologie: revue internationale de physio-biologie et de pharmacologie appliquees aux effets de l’agression. 1970;11(6):495-500.
Kling MA, Manowitz P, Pollack IW. Rat brain and serum lithium concentrations after acute injections of lithium carbonate and orotate. Journal of Pharmacy and Pharmacology. 1978;30(6):368-370. https://doi.org/10.1111/j.2042-7158.1978.tb13258.x
Smith DF, Schou M. Kidney function and lithium concentrations of rats given an injection of lithium orotate or lithium carbonate. Journal of Pharmacy and Pharmacology. 1979;31(3):161-163. https://doi.org/10.1111/j.2042-7158.1979.tb13461.x
Harkevich DA. Pharmacology: textbook. M.: GEOTAR-Media; 2021. (In Russ.).
Lewitzka U, Severus E, Bauer R, et al. The suicide prevention effect of lithium: more than 20 years of evidence-a narrative review. Int J Bipolar Disord. 2015;3(1):32. https://doi.org/10.1186/s40345-015-0032-2
Klein PS, Melton DA. A molecular mechanism for the effect of lithium on development. Proc Natl Acad Sci USA. 1996;93(16):8455-8459. https://doi.org/10.1073/pnas.93.16.8455
Damri O, Sade Y, Toker L, et al. Molecular effects of lithium are partially mimicked by inositol-monophosphatase (IMPA)1 knockout mice in a brain region-dependent manner. Eur Neuropsychopharmacol. 2015;25(3):425-434. https://doi.org/10.1016/j.euroneuro.2014.06.012
Hallcher LM, Sherman WR. The effects of lithium ion and other agents on the activity of myo-inositol-1-phosphatase from bovine brain. J Biol Chem. 1980;255:10896-10901.
Ma J, Zhang GY. Lithium reduced N-methyl-D-aspartate receptor subunit 2A tyrosine phosphorylation and its interactions with Src and Fyn mediated by PSD-95 in rat hippocampus following cerebral ischemia. Neurosci Lett. 2003;348(3):185-189. https://doi.org/10.1016/s0304-3940(03)00784-5
Aubry JM, Schwald M, Ballmann E, et al. Early effects of mood stabilizers on the Akt/GSK-3beta signaling pathway and on cell survival and proliferation. Psychopharmacology (Berl). 2009;205(3):419-429. https://doi.org/10.1007/s00213-009-1551-2
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):6039-6042. https://doi.org/10.1074/jbc.274.10.6039
Hiroi T, Wei H, Hough C, et al. 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):102-111. https://doi.org/10.1038/sj.tpj.6500296
Farre JC, Subramani S. Peroxisome turnover by micropexophagy: an autophagy-related process. Trends Cell Biol. 2004;14:515-523. https://doi.org/10.1016/j.tcb.2004.07.014
Uttenweiler A, Mayer A. Microautophagy in the yeast Saccharomyces cerevisiae. Methods Mol Biol. 2008;445:245-259. https://doi.org/10.1007/978-1-59745-157-4_16
Levine B, Klionsky DJ. Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell. 2004;6:463-477. https://doi.org/10.1016/s1534-5807(04)00099-1
Wang QJ, Ding Y, Kohtz DS, et al. Induction of autophagy in axonal dystrophy and degeneration. J Neurosci. 2006;26:8057-8068. https://doi.org/10.1523/JNEUROSCI.2261-06.2006
Levine B, Kroemer G. Autophagy in the pathogenesis of disease. Cell. 2008;132:27-42. https://doi.org/10.1016/j.cell.2007.12.018
Hou L, Xiong N, Liu L, et al. Lithium protects dopaminergic cells from rotenone toxicity via autophagy enhancement. BMC Neurosci. 2015;16:82. https://doi.org/10.1186/s12868-015-0222-y
Kazemi H, Noori-Zadeh A, Darabi S, et al. Lithium prevents cell apoptosis through autophagy induction. Bratisl Lek Listy. 2018;119(4):234-239. https://doi.org/10.4149/BLL_2018_044
Gomez-Ramos A, Abad X, Fanarraga ML, et al. Expression of an altered form of tau in Sf9 insect cells results in the assembly of polymers resembling Alzheimer’s paired helical filaments. Brain Res. 2004;1007:57-64. https://doi.org/10.1016/j.brainres.2004.01.071
Sun X, Sato S, Murayama O, et al. Lithium inhibits amyloid secretion in COS7 cells transfected with amyloid precursor protein C100. Neurosci Lett. 2002;321:61-64. https://doi.org/10.1016/s0304-3940(01)02583-6
De Ferrari GV, Chacon MA, Barria MI, et al. Activation of Wnt signaling rescues neurodegeneration and behavioral impairments induced by beta-amyloid fibrils. Mol Psychiatry. 2003;8:195-208. https://doi.org/10.1038/sj.mp.4001208
Rametti A, Esclaire F, Yardin C, et al. Lithium down-regulates tau in cultured cortical neurons: A possible mechanism of neuroprotection. Neurosci Lett. 2008;434:93-98. https://doi.org/10.1016/j.neulet.2008.01.034
Rametti A, Esclaire F, Yardin C, et al. Linking alterations in tau phosphorylation and cleavage during neuronal apoptosis. J Biol Chem. 2004;279:54518-54528. https://doi.org/10.1074/jbc.M408186200
Yu F, Zhang Y, Chuang DM. Lithium reduces BACE1 overexpression, beta amyloid accumulation, and spatial learning deficit in mice with traumatic brain injury. J Neurotrauma. 2012;29:2342-2351. https://doi.org/10.1089/neu.2012.2449
Sofola O, Kerr F, Rogers I, et al. Inhibition of GSK-3 ameliorates Abeta pathology in an adult-onset Drosophila model of Alzheimer’s disease. PLoS Genet. 2010;6:e1001087. https://doi.org/10.1371/journal.pgen.1001087
Mudher A, Shepherd D, Newman TA, et al. GSK-3beta inhibition reverses axonal transport defects and behavioural phenotypes in Drosophila. Mol Psychiatry. 2004;9:522-530. https://doi.org/10.1038/sj.mp.4001483
Trujillo-Estrada L, Jimenez S, De Castro V, et al. In vivo modification of Abeta plaque toxicity as a novel neuroprotective lithium-mediated therapy for Alzheimer’s disease pathology. Acta Neuropathol Commun. 2013;1:73. https://doi.org/10.1186/2051-5960-1-73
Pan Y, Short JL, Newman SA, et al. Cognitive benefits of lithium chloride in APP/PS1 mice are associated with enhanced brain clearance of beta-amyloid. Brain Behav Immun. 2018;70:36. https://doi.org/10.1016/j.bbi.2018.03.007
Liu M, Qian T, Zhou W, et al. Beneficial effects of low-dose lithium on cognitive ability and pathological alteration of Alzheimer’s disease transgenic mice model. Neuroreport. 2020;31:943-951. https://doi.org/10.1097/WNR.0000000000001499
Pouladi MA, Brillaud E, Xie Y, et al. NP03, a novel low-dose lithium formulation, is neuroprotective in the YAC128 mouse model of Huntington disease. Neurobiol Dis. 2012;48:282-289. https://doi.org/10.1016/j.nbd.2012.06.026
Wilson EN, Do Carmo S, Welikovitch LA, et al. NP03, a microdose lithium formulation, blunts early amyloid post-plaque neuropathology in McGill-R-Thy1-APP Alzheimer-like transgenic rats. J Alzheimer’s Dis. 2020;73:723-739. https://doi.org/10.3233/JAD-190862
Nunes MA, Schowe NM, Monteiro-Silva KC, et al. Chronic microdose lithium treatment prevented memory loss and neurohistopathological changes in a transgenic mouse model of Alzheimer’s disease. PLoS ONE. 2015;10:e0142267. https://doi.org/10.1371/journal.pone.0142267
Vasconcelos-Moreno MP, Fries GR, Gubert C, et al. Telomere Length, Oxidative Stress, Inflammation and BDNF Levels in Siblings of Patients with Bipolar Disorder: Implications for Accelerated Cellular Aging. Int J Neuropsychopharmacol. 2017;20(6):445-454. https://doi.org/10.1093/ijnp/pyx001
Barbé-Tuana FM, Parisi MM, Panizzutti BS, et al. Shortened telomere length in bipolar disorder: a comparison of the early and late stages of disease. Braz J Psychiatry. 2016;38(4):281-286. https://doi.org/10.1590/1516-4446-2016-1910
Huang YC, Wang LJ, Tseng PT, et al. Leukocyte telomere length in patients with bipolar disorder: An updated meta-analysis and subgroup analysis by mood status. Psychiatry Res. 2018;270:41-49. https://doi.org/10.1016/j.psychres.2018.09.035
Martinsson L, Wei Y, Xu D, et al. Long term lithium treatment in bipolar disorder is associated with longer leukocyte telomeres. Transl Psychiatry. 2013;3(5):e261. https://doi.org/10.1038/tp.2013.37
Pisanu C, Congiu D, Manchia M, et al. Differences in telomere length between patients with bipolar disorder and controls are influenced by lithium treatment. Pharmacogenomics. 2020;21(8):533-540. https://doi.org/10.2217/pgs-2020-0028
Köse Çinar R. Telomere length and hTERT in mania and subsequent remission. Braz J Psychiatry. 2018;40(1):19-25. https://doi.org/10.1590/1516-4446-2017-2216
Wei YB, Backlund L, Wegener G, et al. Telomerase dysregulation in the hippocampus of a rat model of depression: normalization by lithium. Int J Europsychopharmacol. 2015;18(7):pyv002. https://doi.org/10.1093/ijnp/pyv002
Lundberg M, Biernacka JM, Lavebratt C, et al. Expression of telomerase reverse transcriptase positively correlates with duration of lithium treatment in bipolar disorder. Psychiatry Res. 2020;286:112865. https://doi.org/10.1016/j.psychres.2020.112865
Niu C, Yip HK. Neuroprotective signaling mechanisms of telomerase are regulated by brain-derived neurotrophic factor in rat spinal cord motor neurons. J Neuropathol Exp Neurol. 2011;70(7):634-652. https://doi.org/10.1097/NEN.0b013e318222b97b
Terao T, Nakano H, Inoue Y, et al. Lithium and dementia: A preliminary study. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30:1125-1128. https://doi.org/10.1016/j.pnpbp.2006.04.020
Nunes PV, Forlenza OV, Gattaz WF. Lithium and risk for AD in elderly patients with bipolar disorder. Br J Psychiatry. 2007;190:359-360. https://doi.org/10.1192/bjp.bp.106.029868
Hampel H, Ewers M, Berger K, et al. Lithium trial in Alzheimer’s disease: A randomized, single-blind, placebo-controlled, multicenter 10-week study. J Clin Psychiatry. 2009;70:922-931.
Kessing LV, Forman JL, Andersen PK. Does lithium protect against dementia? Bipolar Disord. 2010;12:87-94. https://doi.org/10.1111/j.1399-5618.2009.00788.x
Gerhard T, Devanand DP, Huang C, et al. Lithium treatment and risk for dementia in adults with bipolardisorder: Population-based cohort study. Br J Psychiatry. 2015;207:46-51. https://doi.org/10.1192/bjp.bp.114.154047
Forlenza OV, Radanovic M, Talib LL, et al. Clinical and biological effects of long-term lithium treatment in older adults with amnestic mild cognitive impairment: Randomised clinical trial. Br J Psychiatry. 2019;215:668-674. https://doi.org/10.1192/bjp.2019.76
Nunes MA, Viel TA, Buck HS. Microdose lithium treatment stabilized cognitive impairment in patients with Alzheimer’s disease. Curr Alzheimer Res. 2013;10:104-107. https://doi.org/10.2174/1567205011310010014
Pepelyaev EG, Gromova OA, Semenov VA, Yanko EV. Interrelation of development of cognitive disturbances with lithium level in an organism at middle-aged persons. Klinicheskaya Nevrologiya. 2019;1:30-33. (In Russ.).
Kessing LV, Gerds TA, Knudsen NN, et al. Association of Lithium in DrinkingWaterWith the Incidence of Dementia. JAMA Psychiatry. 2017;74:1005-1010. https://doi.org/10.1001/jamapsychiatry.2017.2362
Fajardo VA, Fajardo VA, LeBlanc PJ, et al. Examining the Relationship between Trace Lithium in Drinking Water and the Rising Rates of Age-Adjusted AD Mortality in Texas. J Alzheimers Dis. 2018;61:425-434. https://doi.org/10.3233/JAD-170744
Schrauzer GN, Shrestha KP. Lithium in drinking water and the incidences of crimes, suicides, and arrests related to drug addictions. Biol Trace Elem Res. 1990;25(2):105-113. https://doi.org/10.1007/BF02990271
Barjasteh-Askari F, Davoudi M, Amini H, et al. Relationship between suicide mortality and lithium in drinking water: A systematic review and meta-analysis. J Affect Disord. 2020;264:234-241. https://doi.org/10.1016/j.jad.2019.12.027
Torshin IYu, Sardaryan IS, Gromova OA, et al. Chemoreactome modeling the effects of anions of lithium salts ascorbate, nicotinate, hydroxybutyrate komenata and lithium carbonate. Farmakokinetika i Farmakodinamika. 2016;3:47-57. (In Russ.).
Pronin AV, Gromova OA, Torshin IYu, et al. Preclinical study the pharmacokinetics of lithium ascorbate. Farmakokinetika i Farmakodinamika. 2016;2:18-25. (In Russ.).
Ostrenko KV, Gromova OA, Sardaryan IS, et al. The effectiveness of lithium ascorbate on chronic alcohol intoxication model. Farmakokinetika i Farmakodinamika. 2016;4:31-41. (In Russ.).

Close metadata