Ameliorating Effects of Lithium on the Perinatal Ethanol-Induced Behavioral and Cognitive Dysfunction and Brain Oxidative Stress in Postnatal Developing Mice Pups

Author(s): Mohammad Ahmad, Gasem M. Abu Taweel*

Journal Name: Current Pharmaceutical Biotechnology

Volume 21 , Issue 13 , 2020


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Graphical Abstract:


Abstract:

Background: Developmental ethanol (EtOH) exposure can cause lifelong behavioral hyperactivity, cognitive deficits, emotional dysregulation, and more. However, co-treatment with lithium (Li) on the day of EtOH exposure prevents many of the impairments.

Methods: Experimental groups of pregnant mice were exposed to EtOH (20% v/v solution at a dose of 2.5 g/kg) in their drinking water and the animals were treated with Li (15 and 30 mg/kg) through IP injection on gestational days14, 16, 18, and 20, and post-natal days (PD) 3, 5, 7, and 9. All treatments with EtOH and exposure to Li doses to pregnant mice started on gestational day 14 and continued until post-natal day 9 (PD9). The effects on some developing morphological indices, nerve reflexes during weaning age, and various cognitive dysfunctions at adolescent ages and biochemical changes in the brain tissue indices of below-mentioned neurotransmitters and oxidative stress in post-natal developing offspring at adolescent age, were studied.

Results: Perinatal exposure to EtOH in pregnant mice resulted in several postnatal developing and morphological indices in the developing male pups during their weaning period, like gain in their body weight, delay in appearance of their body hair fuzz and opening of their eyes, and disruptions in their developing motor reflexes.

Discussion: During adolescent age, a significant deficit in their learning capability and cognitive behavior, decline in the neurochemical DA and 5-HT in their brain and some indices of oxidative stress TBARS, GSH, GST, CAT, and SOD was observed.

Conclusion: These results indicate that Li ameliorates significantly and dose-dependently EtOH induced developmental toxicities like morphological developments and dysfunctions in cognitive retention and oxidative stress on a long-term basis in brain tissue. However, further detailed studies are required for the clinical use of as an ameliorating agent for perinatal EtOH induced dysfunctions.

Keywords: Mice, perinatal, ethanol, lithium, cognitive dysfunctions, brain oxidative stress.

[1]
Riley, E.P.; McGee, C.L. Fetal alcohol spectrum disorders: an overview with emphasis on changes in brain and behavior. Exp. Biol. Med. (Maywood), 2005, 230(6), 357-365.
[http://dx.doi.org/10.1177/15353702-0323006-03] [PMID: 15956765]
[2]
Zhong, J.; Yang, X.; Yao, W.; Lee, W. Lithium protects ethanol-induced neuronal apoptosis. Biochem. Biophys. Res. Commun., 2006, 350(4), 905-910.
[http://dx.doi.org/10.1016/j.bbrc.2006.09.138] [PMID: 17045245]
[3]
Helfer, J.L.; Goodlett, C.R.; Greenough, W.T.; Klintsova, A.Y. The effects of exercise on adolescent hippocampal neurogenesis in a rat model of binge alcohol exposure during the brain growth spurt. Brain Res., 2009, 1294, 1-11.
[http://dx.doi.org/10.1016/j.brainres.2009.07.090] [PMID: 19647724]
[4]
Thomas, J.D.; Idrus, N.M.; Monk, B.R.; Dominguez, H.D. Prenatal choline supplementation mitigates behavioral alterations associated with prenatal alcohol exposure in rats. Birth Defects Res. A Clin. Mol. Teratol., 2010, 88(10), 827-837.
[http://dx.doi.org/10.1002/bdra.20713] [PMID: 20706995]
[5]
Murawski, N.J.; Stanton, M.E. Effects of dose and period of neonatal alcohol exposure on the context preexposure facilitation effect. Alcohol. Clin. Exp. Res., 2011, 35(6), 1160-1170.
[http://dx.doi.org/10.1111/j.1530-0277.2011.01449.x] [PMID: 21352243]
[6]
Patten, A.R.; Fontaine, C.J.; Christie, B.R. A comparison of the different animal models of fetal alcohol spectrum disorders and their use in studying complex behaviors. Front Pediatr., 2014, 2, 93.
[http://dx.doi.org/10.3389/fped.2014.00093] [PMID: 25232537]
[7]
Fontaine, C.J.; Patten, A.R.; Sickmann, H.M.; Helfer, J.L.; Christie, B.R. Effects of pre-natal alcohol exposure on hippocampal synaptic plasticity: Sex, age and methodological considerations. Neurosci. Biobehav. Rev., 2016, 64, 12-34.
[http://dx.doi.org/10.1016/j.neubiorev.2016.02.014] [PMID: 26906760]
[8]
Pies, R. Combining lithium and anticonvulsants in bipolar disorder: a review. Ann. Clin. Psychiatry, 2002, 14(4), 223-232.
[http://dx.doi.org/10.3109/10401230209147461] [PMID: 12630658]
[9]
Chuang, D.M. The antiapoptotic actions of mood stabilizers: Molecular mechanisms and therapeutic potentials. Ann. N. Y. Acad. Sci., 2005, 1053, 195-204.
[http://dx.doi.org/10.1196/annals.1344.018] [PMID: 16179524]
[10]
Marmol, F. Lithium: bipolar disorder and neurodegenerative diseases Possible cellular mechanisms of the therapeutic effects of lithium. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2008, 32(8), 1761-1771.
[http://dx.doi.org/10.1016/j.pnpbp.2008.08.012] [PMID: 18789369]
[11]
Machado-Vieira, R.; Manji, H.K.; Zarate, C.A., Jr The role of lithium in the treatment of bipolar disorder: Convergent evidence for neurotrophic effects as a unifying hypothesis. Bipolar Disord., 2009, 11(Suppl. 2), 92-109.
[http://dx.doi.org/10.1111/j.1399-5618.2009.00714.x] [PMID: 19538689]
[12]
Luo, J. Lithium-mediated protection against ethanol neurotoxicity. Front. Neurosci., 2010, 4, 41.
[PMID: 20661453]
[13]
Wozniak, D.F.; Hartman, R.E.; Boyle, M.P.; Vogt, S.K.; Brooks, A.R.; Tenkova, T.; Young, C.; Olney, J.W.; Muglia, L.J. Apoptotic neurodegeneration induced by ethanol in neonatal mice is associated with profound learning/memory deficits in juveniles followed by progressive functional recovery in adults. Neurobiol. Dis., 2004, 17(3), 403-414.
[http://dx.doi.org/10.1016/j.nbd.2004.08.006] [PMID: 15571976]
[14]
Saito, M.; Chakraborty, G.; Mao, R.F.; Paik, S.M.; Vadasz, C.; Saito, M. Tau phosphorylation and cleavage in ethanol-induced neurodegeneration in the developing mouse brain. Neurochem. Res., 2010, 35(4), 651-659.
[http://dx.doi.org/10.1007/s11064-009-0116-4] [PMID: 20049527]
[15]
Wilson, D.A.; Peterson, J.; Basavaraj, B.S.; Saito, M. Local and regional network function in behaviorally relevant cortical circuits of adult mice following postnatal alcohol exposure. Alcohol. Clin. Exp. Res., 2011, 35(11), 1974-1984.
[http://dx.doi.org/10.1111/j.1530-0277.2011.01549.x] [PMID: 21649667]
[16]
Sadrian, B.; Subbanna, S.; Wilson, D.A.; Basavarajappa, B.S.; Saito, M. Lithium prevents long-term neural and behavioral pathology induced by early alcohol exposure. Neuroscience, 2012, 206, 122-135.
[http://dx.doi.org/10.1016/j.neuroscience.2011.12.059] [PMID: 22266347]
[17]
Abu-Taweel, G.M.; Ajarem, J.S.; Ahmad, M. Neurobehavioral toxic effects of perinatal oral exposure to aluminum on the developmental motor reflexes, learning, memory and brain neurotransmitters of mice offspring. Pharmacol. Biochem. Behav., 2012, 101(1), 49-56.
[http://dx.doi.org/10.1016/j.pbb.2011.11.003] [PMID: 22115621]
[18]
Patrick, O.E.; Hirohisa, M.; Masahira, K.; Koreaki, M. Central nervous system bioaminergic responses to mechanic trauma. Surg. Neurol., 1991, 35, 273-279.
[http://dx.doi.org/10.1016/0090-3019(91)90004-S] [PMID: 2008642]
[19]
Ohkawa, H.; Ohishi, N.; Yagi, K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem., 1979, 95(2), 351-358.
[http://dx.doi.org/10.1016/0003-2697(79)90738-3] [PMID: 36810]
[20]
Mangino, M.J.; Murphy, M.K.; Grabau, G.G.; Anderson, C.B. Protective effects of glycine during hypothermic renal ischemia-reperfusion injury. Am. J. Physiol., 1991, 261(5 Pt 2), F841-F848.
[PMID: 1951715]
[21]
Habig, W.H.; Pabst, M.J.; Jakoby, W.B. Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J. Biol. Chem., 1974, 249(22), 7130-7139.
[PMID: 4436300]
[22]
Aebi, H. Catalase. Methods of Enzymatic Analysis; Bergmeyer, H.U., Ed.; Academic Press: New York, NY, USA, 1974, Vol. 2, pp. 673-684.
[23]
Misra, H.P.; Fridovich, I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J. Biol. Chem., 1972, 247(10), 3170-3175.
[PMID: 4623845]
[24]
Lewin, M.; Ilina, M.; Betz, J.; Masiello, K.; Hui, M.; Wilson, D.A.; Saito, M. Developmental ethanol-induced sleep fragmentation, behavioral hyperactivity, cognitive impairment and parvalbumin cell loss are prevented by lithium co-treatment. Neuroscience, 2018, 369, 269-277.
[http://dx.doi.org/10.1016/j.neuroscience.2017.11.033] [PMID: 29183826]
[25]
Sharma, A.; Rawat, A.K. Teratogenic effects of lithium and ethanol in the developing fetus. Alcohol, 1986, 3(2), 101-106.
[http://dx.doi.org/10.1016/0741-8329(86)90019-4] [PMID: 3087378]
[26]
Petkov, V.D.; Belcheva, S.; Konstantinova, E.; Kehayov, R. Participation of different 5-HT receptors in the memory process in rats and its modulation by the serotonin depletor p-chlorophenylalanine. Acta Neurobiol. Exp. (Warsz.), 1995, 55(4), 243-252.
[PMID: 8713354]
[27]
Tariq, M.; Ahmad, M.; Moutaery, K.A.; Deeb, S.A. Pentoxifylline ameliorates lithium-pilocarpine induced status epilepticus in young rats. Epilepsy Behav., 2008, 12(3), 354-365.
[http://dx.doi.org/10.1016/j.yebeh.2007.12.004] [PMID: 18203664]
[28]
Savage, L.M.; Buzzetti, R.A.; Ramirez, D.R. The effects of hippocampal lesions on learning, memory, and reward expectancies. Neurobiol. Learn. Mem., 2004, 82(2), 109-119.
[http://dx.doi.org/10.1016/j.nlm.2004.05.002] [PMID: 15341796]
[29]
Freitas, R.M. Investigation of oxidative stress involvement in hippocampus in epilepsy model induced by pilocarpine. Neurosci. Lett., 2009, 462(3), 225-229.
[http://dx.doi.org/10.1016/j.neulet.2009.07.037] [PMID: 19616071]
[30]
Reeta, K.H.; Mehla, J.; Gupta, Y.K. Curcumin is protective against phenytoin-induced cognitive impairment and oxidative stress in rats. Brain Res., 2009, 1301, 52-60.
[http://dx.doi.org/10.1016/j.brainres.2009.09.027] [PMID: 19765566]


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Article Details

VOLUME: 21
ISSUE: 13
Year: 2020
Page: [1325 - 1332]
Pages: 8
DOI: 10.2174/1389201021666200615170644
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