Abstract
Thimerosal (THIM) induces neurotoxic changes including neuronal death and releases apoptosis inducing factors from mitochondria to cytosol. THIM alters the expression level of factors involved in apoptosis. On the other hand, the anti-apoptotic effects of exercise have been reported. In this study, we aimed to discover the effect of three protocols of treadmill exercise on the expression level of mitochondrial transcription factor A (TFAM), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), BCL-2-associated death (BAD), BCL-2-associated X (BAX), BCL-XL, and BCL-2 (a pro-survival BCL-2 protein) in the hippocampus of control and THIM-exposed rats. Male Wistar rats were used in this research. Real-time PCR was applied to assess genes expression. The results showed that THIM increased the expression of pro-apoptotic factors (BAD and BAX), decreased the expression of anti-apoptotic factors (BCL-2 and BCL-XL), and decreased the expression of factors involved in mitochondrial biogenesis (TFAM and PGC-1α). Treadmill exercise protocols reversed the effect of THIM on all genes. In addition, treadmill exercise protocols decreased the expression of BAD and BAX, increased the expression of BCL-2, and increased the expression of TFAM and PGC-1α in control rats. In conclusion, THIM induced a pro-apoptotic effect and disturbed mitochondrial biogenesis and stability, whereas treadmill exercise reversed these effects.
Similar content being viewed by others
References
Abdelzaher LA, Hussein OA, Ashry IEM (2020) The novel potential therapeutic utility of montelukast in alleviating autistic behavior induced by early postnatal administration of thimerosal in mice. Cell Mol Neurobiol. https://doi.org/10.1007/s10571-020-00841-2
Afsordeh K, Sadeghi Y, Amini A, Namvarpour Z, Abdollahifar MA, Abbaszadeh HA, Aliaghaei A (2019) Alterations of neuroimmune cell density and pro-inflammatory cytokines in response to thimerosal in prefrontal lobe of male rats. Drug Chem Toxicol 42:176–186. https://doi.org/10.1080/01480545.2018.1465949
Aguiar AS Jr et al (2016) Moderate-intensity physical exercise protects against experimental 6-hydroxydopamine-induced hemiparkinsonism through Nrf2-antioxidant response element pathway. Neurochem Res 41:64–72. https://doi.org/10.1007/s11064-015-1709-8
Aguilo A, Tauler P, Fuentespina E, Tur JA, Cordova A, Pons A (2005) Antioxidant response to oxidative stress induced by exhaustive exercise. Physiol Behav 84:1–7. https://doi.org/10.1016/j.physbeh.2004.07.034
Ahmadalipour A, Rashidy-Pour A (2015) Effects of treadmill running exercise during the adolescent period of life on behavioral deficits in juvenile rats induced by prenatal morphine exposure. Physiol Behav 139:26–33. https://doi.org/10.1016/j.physbeh.2014.10.038
Alam TI et al (2003) Human mitochondrial DNA is packaged with TFAM. Nucleic Acids Res 31:1640–1645. https://doi.org/10.1093/nar/gkg251
Alihemmati A, Ebadi F, Moghadaszadeh M, Asadi M, Zare P, Badalzadeh R (2019) Effects of high-intensity interval training on the expression of microRNA-499 and pro- and anti-apoptotic genes in doxorubicin-cardiotoxicity in rats. J Electrocardiol 55:9–15. https://doi.org/10.1016/j.jelectrocard.2019.02.009
Ashkenazi A, Fairbrother WJ, Leverson JD, Souers AJ (2017) From basic apoptosis discoveries to advanced selective BCL-2 family inhibitors. Nat Rev Drug Discov 16:273–284. https://doi.org/10.1038/nrd.2016.253
Barrett JR (2005) Thimerosal and animal brains: new data for assessing human ethylmercury risk. Environ Health Perspect 113:A543-544
Baskin DS, Ngo H, Didenko VV (2003) Thimerosal induces DNA breaks, caspase-3 activation, membrane damage, and cell death in cultured human neurons and fibroblasts. Toxicol Sci 74:361–368. https://doi.org/10.1093/toxsci/kfg126
Blair A, Clark B, Clarke AJ, Wood P (1975) Tissue concentrations of mercury after chronic dosing of squirrel monkeys with thiomersal. Toxicology 3:171–176. https://doi.org/10.1016/0300-483x(75)90082-7
Bouitbir J et al (2012) Opposite effects of statins on mitochondria of cardiac and skeletal muscles: a 'mitohormesis' mechanism involving reactive oxygen species and PGC-1. Eur Heart J 33:1397–1407. https://doi.org/10.1093/eurheartj/ehr224
Brown LA, Macpherson PC, Koch LG, Qi NR, Britton SL, Brooks SV (2019) Late life maintenance and enhancement of functional exercise capacity in low and high responding rats after low intensity treadmill training. Exp Gerontol 125:110657. https://doi.org/10.1016/j.exger.2019.110657
Brown MB et al (2017) High-intensity interval training, but not continuous training, reverses right ventricular hypertrophy and dysfunction in a rat model of pulmonary hypertension. Am J Physiol Regul Integr Comp Physiol 312:R197-R210. https://doi.org/10.1152/ajpregu.00358.2016
Cao LM, Dong ZQ, Li Q, Chen X (2019) Treadmill training improves neurological deficits and suppresses neuronal apoptosis in cerebral ischemic stroke rats Neural Regen Res 14:1387–1393. https://doi.org/10.4103/1673-5374.253523
Chae CH, Kim HT (2009) Forced, moderate-intensity treadmill exercise suppresses apoptosis by increasing the level of NGF and stimulating phosphatidylinositol 3-kinase signaling in the hippocampus of induced aging rats. Neurochem Int 55:208–213. https://doi.org/10.1016/j.neuint.2009.02.024
Chatterjee A, O’Keefe C (2010) Current controversies in the USA regarding vaccine safety. Expert Rev Vaccines 9:497–502. https://doi.org/10.1586/erv.10.36
Chaturvedi RK, Flint Beal M (2013) Mitochondrial diseases of the brain. Free Radic Biol Med 63:1–29. https://doi.org/10.1016/j.freeradbiomed.2013.03.018
Chehimi L, Roy V, Jeljeli M, Sakly M (2012) Chronic exposure to mercuric chloride during gestation affects sensorimotor development and later behaviour in rats. Behav Brain Res 234:43–50. https://doi.org/10.1016/j.bbr.2012.06.005
Chen YN, Wang J, Zhang J, Li SJ, He L, Shao DD, Du HY (2013) Effect of thimerosal on the neurodevelopment of premature rats. World J Pediatr 9:356–360. https://doi.org/10.1007/s12519-013-0443-z
Chmura J, Nazar K, Kaciuba-Uscilko H (1994) Choice reaction time during graded exercise in relation to blood lactate and plasma catecholamine thresholds. Int J Sports Med 15:172–176. https://doi.org/10.1055/s-2007-1021042
Coleman MA, Garland T Jr, Marler CA, Newton SS, Swallow JG, Carter PA (1998) Glucocorticoid response to forced exercise in laboratory house mice (Mus domesticus). Physiol Behav 63:279–285. https://doi.org/10.1016/s0031-9384(97)00441-1
Coskun P, Wyrembak J, Schriner SE, Chen HW, Marciniack C, Laferla F, Wallace DC (2012) A mitochondrial etiology of Alzheimer and Parkinson disease. Biochim Biophys Acta 1820:553–564. https://doi.org/10.1016/j.bbagen.2011.08.008
de Las Heras N et al (2018) Chronic exercise improves mitochondrial function and insulin sensitivity in brown adipose tissue Front Physiol 9:1122. https://doi.org/10.3389/fphys.2018.01122
Dorea JG (2011) Integrating experimental (in vitro and in vivo) neurotoxicity studies of low-dose thimerosal relevant to vaccines. Neurochem Res 36:927–938. https://doi.org/10.1007/s11064-011-0427-0
Dorea JG, Farina M, Rocha JB (2013) Toxicity of ethylmercury (and Thimerosal): a comparison with methylmercury. J Appl Toxicol 33:700–711. https://doi.org/10.1002/jat.2855
Ekstrand MI et al (2004) Mitochondrial transcription factor A regulates mtDNA copy number in mammals. Hum Mol Genet 13:935–944. https://doi.org/10.1093/hmg/ddh109
Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35:495–516. https://doi.org/10.1080/01926230701320337
Feizolahi F, Azarbayjani MA, Nasehi M, Peeri M, Zarrindast MR (2019) The combination of swimming and curcumin consumption may improve spatial memory recovery after binge ethanol drinking. Physiol Behav 207:139–150. https://doi.org/10.1016/j.physbeh.2019.03.018
Freitas DA et al (2019) High-intensity interval training improves cerebellar antioxidant capacity without affecting cognitive functions in rats. Behav Brain Res 376:112181. https://doi.org/10.1016/j.bbr.2019.112181
Geier DA, Sykes LK, Geier MR (2007) A review of Thimerosal (Merthiolate) and its ethylmercury breakdown product: specific historical considerations regarding safety and effectiveness. J Toxicol Environ Health B Crit Rev 10:575–596. https://doi.org/10.1080/10937400701389875
Gharebaghi A et al (2017) Treadmill exercise attenuates 3,4-methylenedioxymethamphetamine-induced memory impairment through a decrease apoptosis in male rat hippocampus. J Neurosci Res 95:2448–2455. https://doi.org/10.1002/jnr.24078
Guida N et al (2016) MC1568 inhibits thimerosal-induced apoptotic cell death by preventing HDAC4 up-regulation in neuronal cells and in rat prefrontal cortex. Toxicol Sci 154:227–240. https://doi.org/10.1093/toxsci/kfw157
Han X, Cong H (2017) Enterovirus 71 induces apoptosis by directly modulating the conformational activation of pro-apoptotic protein. Bax J Gen Virol 98:422–434. https://doi.org/10.1099/jgv.0.000705
Harlan JM, Levine JD, Callahan KS, Schwartz BR, Harker LA (1984) Glutathione redox cycle protects cultured endothelial cells against lysis by extracellularly generated hydrogen peroxide. J Clin Invest 73:706–713. https://doi.org/10.1172/JCI111263
Herdman ML, Marcelo A, Huang Y, Niles RM, Dhar S, Kiningham KK (2006) Thimerosal induces apoptosis in a neuroblastoma model via the cJun N-terminal kinase pathway. Toxicol Sci 92:246–253. https://doi.org/10.1093/toxsci/kfj205
Hornig M, Chian D, Lipkin WI (2004) Neurotoxic effects of postnatal thimerosal are mouse strain dependent. Mol Psychiatry 9:833–845. https://doi.org/10.1038/sj.mp.4001529
Hu H, Moller G, Abedi-Valugerdi M (1999) Mechanism of mercury-induced autoimmunity: both T helper 1- and T helper 2-type responses are involved. Immunology 96:348–357. https://doi.org/10.1046/j.1365-2567.1999.00671.x
Huang JB et al (2020) Peroxisome proliferator-activated receptor gamma coactivator 1alpha activates vascular endothelial growth factor that protects against neuronal cell death following status epilepticus through PI3K/AKT and MEK/ERK signaling. Int J Mol Sci 21. https://doi.org/10.3390/ijms21197247
Humphrey ML, Cole MP, Pendergrass JC, Kiningham KK (2005) Mitochondrial mediated thimerosal-induced apoptosis in a human neuroblastoma cell line (SK-N-SH). Neurotoxicology 26:407–416. https://doi.org/10.1016/j.neuro.2005.03.008
Ide T et al (2001) Mitochondrial DNA damage and dysfunction associated with oxidative stress in failing hearts after myocardial infarction. Circ Res 88:529–535. https://doi.org/10.1161/01.res.88.5.529
Javad-Moosavi BZ, Nasehi M, Vaseghi S, Jamaldini SH, Zarrindast MR (2020) Activation and inactivation of nicotinic receptnors in the dorsal hippocampal region restored negative effects of total (TSD) and REM sleep deprivation (RSD) on memory acquisition. Locomotor Activity and Pain Perception Neuroscience 433:200–211. https://doi.org/10.1016/j.neuroscience.2020.03.006
Kang D, Kim SH, Hamasaki N (2007) Mitochondrial transcription factor A (TFAM): roles in maintenance of mtDNA and cellular functions. Mitochondrion 7:39–44. https://doi.org/10.1016/j.mito.2006.11.017
Kanter M, Aksu F, Takir M, Kostek O, Kanter B, Oymagil A (2017) Effects of low intensity exercise against apoptosis and oxidative stress in streptozotocin-induced diabetic rat heart. Exp Clin Endocrinol Diabetes 125:583–591. https://doi.org/10.1055/s-0035-1569332
Kern JK, Geier DA, Homme KG, Geier MR (2020) Examining the evidence that ethylmercury crosses the blood-brain barrier. Environ Toxicol Pharmacol 74:103312. https://doi.org/10.1016/j.etap.2019.103312
Kim TW, Park SS, Shin MS, Park HS, Baek SS (2020) Treadmill exercise ameliorates social isolation-induced memory impairment by enhancing silent information regulator-1 expression in rats. J Exerc Rehabil 16:227–233. https://doi.org/10.12965/jer.2040400.200
Koltai E, Hart N, Taylor AW, Goto S, Ngo JK, Davies KJ, Radak Z (2012) Age-associated declines in mitochondrial biogenesis and protein quality control factors are minimized by exercise training. Am J Physiol Regul Integr Comp Physiol 303:R127-134. https://doi.org/10.1152/ajpregu.00337.2011
Konopka AR, Suer MK, Wolff CA, Harber MP (2014) Markers of human skeletal muscle mitochondrial biogenesis and quality control: effects of age and aerobic exercise training. J Gerontol A Biol Sci Med Sci 69:371–378. https://doi.org/10.1093/gerona/glt107
Kunkel GH, Kunkel CJ, Ozuna H, Miralda I, Tyagi SC (2019) TFAM overexpression reduces pathological cardiac remodeling. Mol Cell Biochem 454:139–152. https://doi.org/10.1007/s11010-018-3459-9
Li FH, Yu HT, Xiao L, Liu YY (2016) Response of BAX, Bcl-2 proteins, and SIRT1/PGC-1alpha mRNA expression to 8-week treadmill running in the aging rat skeletal muscle. Adv Exp Med Biol 923:283–289. https://doi.org/10.1007/978-3-319-38810-6_38
Li WX, Chen SF, Chen LP, Yang GY, Li JT, Liu HZ, Zhu W (2012) Thimerosal-induced apoptosis in mouse C2C12 myoblast cells occurs through suppression of the PI3K/Akt/survivin pathway. PLoS One 7:e49064. https://doi.org/10.1371/journal.pone.0049064
Mahboubi S, Nasehi M, Imani A, Sadat-Shirazi MS, Zarrindast MR, Vousooghi N, Noroozian M (2019) Benefit effect of REM-sleep deprivation on memory impairment induced by intensive exercise in male wistar rats: with respect to hippocampal BDNF and TrkB Nat Sci. Sleep 11:179–188. https://doi.org/10.2147/NSS.S207339
Makani S, Gollapudi S, Yel L, Chiplunkar S, Gupta S (2002) Biochemical and molecular basis of thimerosal-induced apoptosis in T cells: a major role of mitochondrial pathway. Genes Immun 3:270–278. https://doi.org/10.1038/sj.gene.6363854
Malboosi N, Nasehi M, Hashemi M, Vaseghi S, Zarrindast MR (2020) The neuroprotective effect of NeuroAid on morphine-induced amnesia with respect to the expression of TFAM, PGC-1alpha. DeltafosB and CART genes in the hippocampus of male Wistar rats Gene 742:144601. https://doi.org/10.1016/j.gene.2020.144601
Maruta H, Yamashita H (2020) Acetic acid stimulates G-protein-coupled receptor GPR43 and induces intracellular calcium influx in L6 myotube cells. PLoS One 15:e0239428. https://doi.org/10.1371/journal.pone.0239428
Monir DM, Mahmoud ME, Ahmed OG, Rehan IF, Abdelrahman A (2020) Forced exercise activates the NrF2 pathway in the striatum and ameliorates motor and behavioral manifestations of Parkinson's disease in rotenone-treated rats. Behav Brain Funct 16:9. https://doi.org/10.1186/s12993-020-00171-9
Mutkus L, Aschner JL, Syversen T, Shanker G, Sonnewald U, Aschner M (2005) In vitro uptake of glutamate in GLAST- and GLT-1-transfected mutant CHO-K1 cells is inhibited by the ethylmercury-containing preservative thimerosal. Biol Trace Elem Res 105:71–86. https://doi.org/10.1385/BTER:105:1-3:071
Namvarpour Z, Nasehi M, Amini A, Zarrindast MR (2018) Protective role of alpha-lipoic acid in impairments of social and stereotyped behaviors induced by early postnatal administration of thimerosal in male rat. Neurotoxicol Teratol 67:1–9. https://doi.org/10.1016/j.ntt.2018.02.002
Nasehi M, Torabinejad S, Hashemi M, Vaseghi S, Zarrindast MR (2020) Effect of cholestasis and NeuroAid treatment on the expression of Bax, Bcl-2, Pgc-1alpha and Tfam genes involved in apoptosis and mitochondrial biogenesis in the striatum of male rats. Metab Brain Dis 35:183–192. https://doi.org/10.1007/s11011-019-00508-y
Noshadian M et al (2020) Alpha lipoic acid ameliorates THIM-induced prefrontal cell loss and abnormal enzymatically contents in the developing rat. J Chem Neuroanat 103:101727. https://doi.org/10.1016/j.jchemneu.2019.101727
Olczak M, Duszczyk M, Mierzejewski P, Meyza K, Majewska MD (2011) Persistent behavioral impairments and alterations of brain dopamine system after early postnatal administration of thimerosal in rats. Behav Brain Res 223:107–118. https://doi.org/10.1016/j.bbr.2011.04.026
Pan G et al (2021) Intensive treadmill training promotes cognitive recovery after cerebral ischemia-reperfusion in juvenile rats. Behav Brain Res 401:113085. https://doi.org/10.1016/j.bbr.2020.113085
Pan G et al (2020a) Treadmill exercise improves neurological function by inhibiting autophagy and the binding of HMGB1 to Beclin1 in MCAO juvenile rats. Life Sci 243:117279. https://doi.org/10.1016/j.lfs.2020.117279
Pan G et al (2020b) Treadmill exercise attenuates cerebral ischaemic injury in rats by protecting mitochondrial function via enhancement of caveolin-1. Life Sci:118634. https://doi.org/10.1016/j.lfs.2020.118634
Parran DK, Barker A, Ehrich M (2005) Effects of thimerosal on NGF signal transduction and cell death in neuroblastoma cells. Toxicol Sci 86:132–140. https://doi.org/10.1093/toxsci/kfi175
Pedrozo-Penafiel MJ, Miranda-Andrades JR, Gutierrez-Beleno LM, Larrude DG, Aucelio RQ (2020) Indirect voltammetric determination of thiomersal in influenza vaccine using photo-degradation and graphene quantum dots modified glassy carbon electrode. Talanta 215:120938. https://doi.org/10.1016/j.talanta.2020.120938
Pistritto G, Trisciuoglio D, Ceci C, Garufi A, D'Orazi G (2016) Apoptosis as anticancer mechanism: function and dysfunction of its modulators and targeted therapeutic strategies. Aging (Albany NY) 8:603–619. https://doi.org/10.18632/aging.100934
Pless R, Risher JF (2000) Mercury, infant neurodevelopment, and vaccination. J Pediatr 136:571–573. https://doi.org/10.1067/mpd.2000.106797
Polster BM, Fiskum G (2004) Mitochondrial mechanisms of neural cell apoptosis. J Neurochem 90:1281–1289. https://doi.org/10.1111/j.1471-4159.2004.02572.x
Radak Z et al (2001) Regular exercise improves cognitive function and decreases oxidative damage in rat brain. Neurochem Int 38:17–23. https://doi.org/10.1016/s0197-0186(00)00063-2
Rauf S, Soesatyo MH, Agustiningsih D, Partadiredja G (2020) Moderate intensity intermittent exercise upregulates neurotrophic and neuroprotective genes expression and inhibits Purkinje cell loss in the cerebellum of ovariectomized rats. Behav Brain Res 382:112481. https://doi.org/10.1016/j.bbr.2020.112481
Rice KM, Walker EM Jr, Wu M, Gillette C, Blough ER (2014) Environmental mercury and its toxic effects J Prev Med. Public Health 47:74–83. https://doi.org/10.3961/jpmph.2014.47.2.74
Serviddio G et al (2004) Ursodeoxycholic acid protects against secondary biliary cirrhosis in rats by preventing mitochondrial oxidative stress. Hepatology 39:711–720. https://doi.org/10.1002/hep.20101
Shoshan-Barmatz V, Mizrachi D, Keinan N (2013) Oligomerization of the mitochondrial protein VDAC1: from structure to function and cancer therapy. Prog Mol Biol Transl Sci 117:303–334. https://doi.org/10.1016/B978-0-12-386931-9.00011-8
Szumanska G, Gadamski R, Albrecht J (1993) Changes of the Na/K ATPase activity in the cerebral cortical microvessels of rat after single intraperitoneal administration of mercuric chloride: histochemical demonstration with light and electron microscopy. Acta Neuropathol 86:65–70. https://doi.org/10.1007/BF00454900
Tan M, Parkin JE (2000) Route of decomposition of thiomersal (thimerosal). Int J Pharm 208:23–34. https://doi.org/10.1016/s0378-5173(00)00514-7
Teixeira FB et al (2018) Exposure to inorganic mercury causes oxidative stress. Cell Death, and Functional Deficits in the Motor Cortex Front Mol Neurosci 11:125. https://doi.org/10.3389/fnmol.2018.00125
Teixeira FB et al (2014) Evaluation of the effects of chronic intoxication with inorganic mercury on memory and motor control in rats. Int J Environ Res Public Health 11:9171–9185. https://doi.org/10.3390/ijerph110909171
Terashi T et al (2019) Neuroprotective effects of different frequency preconditioning exercise on neuronal apoptosis after focal brain ischemia in rats. Neurol Res 41:510–518. https://doi.org/10.1080/01616412.2019.1580458
Theilen NT, Kunkel GH, Tyagi SC (2017) The role of exercise and TFAM in preventing skeletal muscle atrophy. J Cell Physiol 232:2348–2358. https://doi.org/10.1002/jcp.25737
Tiao MM et al (2009) Early transcriptional deregulation of hepatic mitochondrial biogenesis and its consequent effects on murine cholestatic liver injury. Apoptosis 14:890–899. https://doi.org/10.1007/s10495-009-0357-3
Ueha-Ishibashi T et al (2005) Flow-cytometric analysis on cytotoxic effect of thimerosal, a preservative in vaccines, on lymphocytes dissociated from rat thymic glands. Toxicol In Vitro 19:191–198. https://doi.org/10.1016/j.tiv.2004.07.004
Vasconcelos-Filho FSL et al (2020) Neuroprotector effect of daily 8-minutes of high-intensity interval training in rat abeta1–42 alzheimer disease model. Curr Alzheimer Res 17:1320–1333. https://doi.org/10.2174/1567205018666210218161856
Vaseghi S, Babapour V, Nasehi M, Zarrindast MR (2019) Synergistic but not additive effect between ACPA and lithium in the dorsal hippocampal region on spatial learning and memory in rats: isobolographic analyses. Chem Biol Interact 315:108895. https://doi.org/10.1016/j.cbi.2019.108895
Villena JA (2015) New insights into PGC-1 coactivators: redefining their role in the regulation of mitochondrial function and beyond. FEBS J 282:647–672. https://doi.org/10.1111/febs.13175
Vogtle FN et al (2012) Intermembrane space proteome of yeast mitochondria. Mol Cell Proteomics 11:1840–1852. https://doi.org/10.1074/mcp.M112.021105
Wang T, Yang Z, Zhang Y, Zhang X, Wang L, Zhang S, Jia L (2018) Caspase cleavage of Mcl-1 impairs its anti-apoptotic activity and proteasomal degradation in non-small lung cancer cells. Apoptosis 23:54–64. https://doi.org/10.1007/s10495-017-1436-5
Woo KJ et al (2006) Thimerosal induces apoptosis and G2/M phase arrest in human leukemia cells. Mol Carcinog 45:657–666. https://doi.org/10.1002/mc.20202
Wu Y, Deng F, Wang J, Liu Y, Zhou W, Qu L, Cheng M (2020) Intensity-dependent effects of consecutive treadmill exercise on spatial learning and memory through the p-CREB/BDNF/NMDAR signaling in hippocampus. Behav Brain Res 386:112599. https://doi.org/10.1016/j.bbr.2020.112599
Yap JL, Chen L, Lanning ME, Fletcher S (2017) Expanding the cancer arsenal with targeted therapies: disarmament of the antiapoptotic bcl-2 proteins by small molecules. J Med Chem 60:821–838. https://doi.org/10.1021/acs.jmedchem.5b01888
Yel L, Brown LE, Su K, Gollapudi S, Gupta S (2005) Thimerosal induces neuronal cell apoptosis by causing cytochrome c and apoptosis-inducing factor release from mitochondria. Int J Mol Med 16:971–977
Yole M, Wickstrom M, Blakley B (2007) Cell death and cytotoxic effects in YAC-1 lymphoma cells following exposure to various forms of mercury Toxicology 231:40–57 https://doi.org/10.1016/j.tox.2006.11.062
Zagaar M, Alhaider I, Dao A, Levine A, Alkarawi A, Alzubaidy M, Alkadhi K (2012) The beneficial effects of regular exercise on cognition in REM sleep deprivation: behavioral, electrophysiological and molecular evidence Neurobiol Dis 45:1153–1162. https://doi.org/10.1016/j.nbd.2011.12.039
Zhang L et al (2017) The pan-Bcl2 inhibitor at101 activates the intrinsic apoptotic pathway and causes dna damage in acute myeloid leukemia stem-like cells target. Oncol 12:677–687. https://doi.org/10.1007/s11523-017-0509-2
Author information
Authors and Affiliations
Contributions
P. Navazani conducted the experiments. S. Vaseghi wrote the manuscript, managed the literature search, and revised the manuscript. M. Hashemi conducted real-time PCR experiments. MR. Shafaati analyzed data. M. Nasehi designed the study. The authors declare that all data were generated in-house and that no paper mill was used.
Corresponding author
Ethics declarations
Informed Consent
Informed consent was obtained from all individual participants included in the study.
Conflict of Interest
The authors declare no competing interests.
Research Involving Human Participants and/or Animals
All procedures and protocols used in the study were in accordance with the Institute for Cognitive Science Studies (ICSS) guidelines and with the National Institutes of Health Guide for the Care and Use of Laboratory Animals.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Navazani, P., Vaseghi, S., Hashemi, M. et al. Effects of Treadmill Exercise on the Expression Level of BAX, BAD, BCL-2, BCL-XL, TFAM, and PGC-1α in the Hippocampus of Thimerosal-Treated Rats. Neurotox Res 39, 1274–1284 (2021). https://doi.org/10.1007/s12640-021-00370-w
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12640-021-00370-w