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Aging and Disease    2017, Vol. 8 Issue (1) : 17-30     DOI: 10.14336/AD.2016.1010
Original Article |
Metformin Impairs Spatial Memory and Visual Acuity in Old Male Mice
Nopporn Thangthaeng,Margaret Rutledge,Jessica M. Wong,Philip H. Vann,Michael J. Forster,Nathalie Sumien
Center for Neuroscience Discovery, Institute for Healthy Aging, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX 76107 USA.
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Metformin is an oral anti-diabetic used as first-line therapy for type 2 diabetes. Because benefits of metformin extend beyond diabetes to other age-related pathology, and because its effect on gene expression profiles resembles that of caloric restriction, metformin has a potential as an anti-aging intervention and may soon be assessed as an intervention to extend healthspan. However, beneficial actions of metformin in the central nervous system have not been clearly established. The current study examined the effect of chronic oral metformin treatment on motor and cognitive function when initiated in young, middle-aged, or old male mice. C57BL/6 mice aged 4, 11, or 22 months were randomly assigned to either a metformin group (2 mg/ml in drinking water) or a control group. The mice were monitored weekly for body weight, as well as food and water intake and a battery of behavioral tests for motor, cognitive and visual function was initiated after the first month of treatment. Liver, hippocampus and cortex were collected at the end of the study to assess redox homeostasis. Overall, metformin supplementation in male mice failed to affect blood glucose, body weights and redox homeostasis at any age. It also had no beneficial effect on age-related declines in psychomotor, cognitive or sensory functions. However, metformin treatment had a deleterious effect on spatial memory and visual acuity, and reduced SOD activity in brain regions. These data confirm that metformin treatment may be associated with deleterious effect resulting from the action of metformin on the central nervous system.

Keywords metformin      antidiabetic      aging      cognition      visual function      redox stress      antioxidant enzymes     
Corresponding Authors: Michael J. Forster,Nathalie Sumien   
Issue Date: 01 February 2017
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Nopporn Thangthaeng
Margaret Rutledge
Jessica M. Wong
Philip H. Vann
Michael J. Forster
Nathalie Sumien
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Nopporn Thangthaeng,Margaret Rutledge,Jessica M. Wong, et al. Metformin Impairs Spatial Memory and Visual Acuity in Old Male Mice[J]. A&D, 2017, 8(1): 17-30.
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[1] Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, et al. (2012). Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes care, 35: 1364-1379
[2] Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, et al. (2009). Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes care, 32: 193-203
[3] Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, et al. (2001). Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest, 108: 1167-1174
[4] Larsson O, Morita M, Topisirovic I, Alain T, Blouin MJ, Pollak M, et al. (2012). Distinct perturbation of the translatome by the antidiabetic drug metformin. Proc Natl Acad Sci U S A, 109: 8977-8982
[5] El-Mir MY, Nogueira V, Fontaine E, Averet N, Rigoulet M, Leverve X (2000). Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I. J Biol Chem, 275: 223-228
[6] Owen MR, Doran E, Halestrap AP (2000). Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem J, 348 (Pt 3): 607-614
[7] Madiraju AK, Erion DM, Rahimi Y, Zhang XM, Braddock DT, Albright RA, et al. (2014). Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. Nature, 510: 542-546
[8] Duca FA, Cote CD, Rasmussen BA, Zadeh-Tahmasebi M, Rutter GA, Filippi BM, et al. (2015). Metformin activates a duodenal Ampk-dependent pathway to lower hepatic glucose production in rats. Nature medicine, 21: 506-511
[9] An H, He L (2016). Current understanding of metformin effect on the control of hyperglycemia in diabetes. The Journal of endocrinology, 228: R97-R106
[10] Shin NR, Lee JC, Lee HY, Kim MS, Whon TW, Lee MS, et al. (2014). An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut, 63: 727-735
[11] Hattori Y, Suzuki K, Hattori S, Kasai K (2006). Metformin inhibits cytokine-induced nuclear factor kappaB activation via AMP-activated protein kinase activation in vascular endothelial cells. Hypertension, 47: 1183-1188
[12] Chae YK, Arya A, Malecek MK, Shin DS, Carneiro B, Chandra S, et al. (2016). Repurposing metformin for cancer treatment: current clinical studies. Oncotarget,
[13] Pryor R, Cabreiro F (2015). Repurposing metformin: an old drug with new tricks in its binding pockets. Biochem J, 471: 307-322
[14] Bost F, Sahra IB, Le Marchand-Brustel Y, Tanti JF (2012). Metformin and cancer therapy. Current opinion in oncology, 24: 103-108
[15] Gallagher EJ, LeRoith D (2011). Diabetes, cancer, and metformin: connections of metabolism and cell proliferation. Annals of the New York Academy of Sciences, 1243: 54-68
[16] Hundal RS, Inzucchi SE (2003). Metformin: new understandings, new uses. Drugs, 63: 1879-1894
[17] Eurich DT, Majumdar SR, McAlister FA, Tsuyuki RT, Johnson JA (2005). Improved clinical outcomes associated with metformin in patients with diabetes and heart failure. Diabetes care, 28: 2345-2351
[18] Scarpello JH (2003). Improving survival with metformin: the evidence base today. Diabetes Metab, 29: 6S36-43
[19] Dhahbi JM, Mote PL, Fahy GM, Spindler SR (2005). Identification of potential caloric restriction mimetics by microarray profiling. Physiol Genomics, 23: 343-350
[20] Spindler SR (2006). Use of microarray biomarkers to identify longevity therapeutics. Aging Cell, 5: 39-50
[21] Onken B, Driscoll M (2010). Metformin induces a dietary restriction-like state and the oxidative stress response to extend C. elegans Healthspan via AMPK, LKB1, and SKN-1. PloS one, 5: e8758
[22] Sykiotis GP, Bohmann D (2010). Stress-activated cap’n’collar transcription factors in aging and human disease. Science signaling, 3: re3
[23] Miller RA, Birnbaum MJ (2010). An energetic tale of AMPK-independent effects of metformin. J Clin Invest, 120: 2267-2270
[24] Martin-Montalvo A, Mercken EM, Mitchell SJ, Palacios HH, Mote PL, Scheibye-Knudsen M, et al. (2013). Metformin improves healthspan and lifespan in mice. Nature communications, 4: 2192
[25] Anisimov VN, Piskunova TS, Popovich IG, Zabezhinski MA, Tyndyk ML, Egormin PA, et al. (2010). Gender differences in metformin effect on aging, life span and spontaneous tumorigenesis in 129/Sv mice. Aging, 2: 945-958
[26] Anisimov VN, Berstein LM, Popovich IG, Zabezhinski MA, Egormin PA, Piskunova TS, et al. (2011). If started early in life, metformin treatment increases life span and postpones tumors in female SHR mice. Aging, 3: 148-157
[27] Novelle MG, Ali A, Dieguez C, Bernier M, de Cabo R (2016). Metformin: A Hopeful Promise in Aging Research. Cold Spring Harb Perspect Med, 6
[28] Tucker GT, Casey C, Phillips PJ, Connor H, Ward JD, Woods HF (1981). Metformin kinetics in healthy subjects and in patients with diabetes mellitus. British journal of clinical pharmacology, 12: 235-246
[29] Labuzek K, Suchy D, Gabryel B, Bielecka A, Liber S, Okopien B (2010). Quantification of metformin by the HPLC method in brain regions, cerebrospinal fluid and plasma of rats treated with lipopolysaccharide. Pharmacol Rep, 62: 956-965
[30] Tasci I (2014). Metformin: good or bad for the brain?. Ann Transl Med, 2: 53
[31] Wang J, Gallagher D, DeVito LM, Cancino GI, Tsui D, He L, et al. (2012). Metformin activates an atypical PKC-CBP pathway to promote neurogenesis and enhance spatial memory formation. Cell stem cell, 11: 23-35
[32] Hsu CC, Wahlqvist ML, Lee MS, Tsai HN (2011). Incidence of dementia is increased in type 2 diabetes and reduced by the use of sulfonylureas and metformin. Journal of Alzheimer’s disease: JAD, 24: 485-493
[33] Moore EM, Mander AG, Ames D, Kotowicz MA, Carne RP, Brodaty H, et al. (2013). Increased risk of cognitive impairment in patients with diabetes is associated with metformin. Diabetes care, 36: 2981-2987
[34] Imfeld P, Bodmer M, Jick SS, Meier CR (2012). Metformin, other antidiabetic drugs, and risk of Alzheimer’s disease: a population-based case-control study. Journal of the American Geriatrics Society, 60: 916-921
[35] Chen Y, Zhou K, Wang R, Liu Y, Kwak YD, Ma T, et al. (2009). Antidiabetic drug metformin (GlucophageR) increases biogenesis of Alzheimer’s amyloid peptides via up-regulating BACE1 transcription. Proc Natl Acad Sci U S A, 106: 3907-3912
[36] DiTacchio KA, Heinemann SF, Dziewczapolski G (2015). Metformin treatment alters memory function in a mouse model of Alzheimer’s disease. Journal of Alzheimer’s disease : JAD, 44: 43-48
[37] Esteghamati A, Eskandari D, Mirmiranpour H, Noshad S, Mousavizadeh M, Hedayati M, et al. (2013). Effects of metformin on markers of oxidative stress and antioxidant reserve in patients with newly diagnosed type 2 diabetes: a randomized clinical trial. Clin Nutr, 32: 179-185
[38] Formoso G, De Filippis EA, Michetti N, Di Fulvio P, Pandolfi A, Bucciarelli T, et al. (2008). Decreased in vivo oxidative stress and decreased platelet activation following metformin treatment in newly diagnosed type 2 diabetic subjects. Diabetes Metab Res Rev, 24: 231-237
[39] Allard JS, Perez EJ, Fukui K, Carpenter P, Ingram DK, de Cabo R (2016). Prolonged metformin treatment leads to reduced transcription of Nrf2 and neurotrophic factors without cognitive impairment in older C57BL/6J mice. Behavioural brain research, 301: 1-9
[40] Garg G, Singh S, Singh AK, Rizvi SI (2016). Metformin alleviates altered erythrocyte redox status during aging in rats. Rejuvenation research,
[41] Reagan-Shaw S, Nihal M, Ahmad N (2008). Dose translation from animal to human studies revisited. The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 22: 659-661
[42] Chaudhari K, Wong JM, Vann PH, Sumien N (2016). Exercise, but not antioxidants, reversed ApoE4-associated motor impairments in adult GFAP-ApoE mice. Behavioural brain research, 305: 37-45
[43] Chaudhari K, Wong JM, Vann PH, Sumien N (2014). Exercise training and antioxidant supplementation independently improve cognitive function in adult male and female GFAP-APOE mice. Journal of Sport and Health Science, 3: 196-205
[44] Shetty RA, Forster MJ, Sumien N (2013). Coenzyme Q(10) supplementation reverses age-related impairments in spatial learning and lowers protein oxidation. Age (Dordr), 35: 1821-1834
[45] Prusky GT, Alam NM, Douglas RM (2006). Enhancement of vision by monocular deprivation in adult mice. The Journal of neuroscience : the official journal of the Society for Neuroscience, 26: 11554-11561
[46] Paoletti F, Mocali A (1990). Determination of superoxide dismutase activity by purely chemical system based on NAD(P)H oxidation. Methods in enzymology, 186: 209-220
[47] Smith IK, Vierheller TL, Thorne CA (1988). Assay of glutathione reductase in crude tissue homogenates using 5,5′-dithiobis(2-nitrobenzoic acid). Anal Biochem, 175: 408-413
[48] Wendel A (1981). Glutathione peroxidase. Methods in enzymology, 77: 325-333
[49] (2009). Ustekinumab: new drug. Suspicion of carcinogenicity: too great a risk for psoriasis patients. Prescrire international, 18: 202-204
[50] Holmgren A (1977). Bovine thioredoxin system. Purification of thioredoxin reductase from calf liver and thymus and studies of its function in disulfide reduction. J Biol Chem, 252: 4600-4606
[51] Arner ES, Bjornstedt M, Holmgren A (1995). 1-Chloro-2,4-dinitrobenzene is an irreversible inhibitor of human thioredoxin reductase. Loss of thioredoxin disulfide reductase activity is accompanied by a large increase in NADPH oxidase activity. J Biol Chem, 270: 3479-3482
[52] Mannervik B (1985). The isoenzymes of glutathione transferase. Advances in enzymology and related areas of molecular biology, 57: 357-417
[53] Boyland E, Chasseaud LF (1969). The role of glutathione and glutathione S-transferases in mercapturic acid biosynthesis. Advances in enzymology and related areas of molecular biology, 32: 173-219
[54] Kim JY, Yim JH, Cho JH, Kim JH, Ko JH, Kim SM, et al. (2006). Adrenomedullin regulates cellular glutathione content via modulation of gamma-glutamate-cysteine ligase catalytic subunit expression. Endocrinology, 147: 1357-1364
[55] Verma S, Bhanot S, McNeill JH (1994). Metformin decreases plasma insulin levels and systolic blood pressure in spontaneously hypertensive rats. The American journal of physiology, 267: H1250-1253
[56] Rosen P, Wiernsperger NF (2006). Metformin delays the manifestation of diabetes and vascular dysfunction in Goto-Kakizaki rats by reduction of mitochondrial oxidative stress. Diabetes Metab Res Rev, 22: 323-330
[57] Sohal RS, Forster MJ (2014). Caloric restriction and the aging process: a critique. Free Radic Biol Med, 73: 366-382
[58] Aghili R, Malek M, Valojerdi AE, Banazadeh Z, Najafi L, Khamseh ME (2014). Body composition in adults with newly diagnosed type 2 diabetes: effects of metformin. J Diabetes Metab Disord, 13: 88
[59] Lv WS, Wen JP, Li L, Sun RX, Wang J, Xian YX, et al. (2012). The effect of metformin on food intake and its potential role in hypothalamic regulation in obese diabetic rats. Brain Res, 1444: 11-19
[60] Aubert G, Mansuy V, Voirol MJ, Pellerin L, Pralong FP (2011). The anorexigenic effects of metformin involve increases in hypothalamic leptin receptor expression. Metabolism: clinical and experimental, 60: 327-334
[61] Malin SK, Kashyap SR (2014). Effects of metformin on weight loss: potential mechanisms. Curr Opin Endocrinol Diabetes Obes, 21: 323-329
[62] Alhaider AA, Korashy HM, Sayed-Ahmed MM, Mobark M, Kfoury H, Mansour MA (2011). Metformin attenuates streptozotocin-induced diabetic nephropathy in rats through modulation of oxidative stress genes expression. Chem Biol Interact, 192: 233-242
[63] Xiao H, Ma X, Feng W, Fu Y, Lu Z, Xu M, et al. (2010). Metformin attenuates cardiac fibrosis by inhibiting the TGFbeta1-Smad3 signalling pathway. Cardiovascular research, 87: 504-513
[64] Fu YN, Xiao H, Ma XW, Jiang SY, Xu M, Zhang YY (2011). Metformin attenuates pressure overload-induced cardiac hypertrophy via AMPK activation. Acta pharmacologica Sinica, 32: 879-887
[65] Calvert JW, Gundewar S, Jha S, Greer JJ, Bestermann WH, Tian R, et al. (2008). Acute metformin therapy confers cardioprotection against myocardial infarction via AMPK-eNOS-mediated signaling. Diabetes, 57: 696-705
[66] Sumien N, Sims MN, Taylor HJ, Forster MJ (2006). Profiling psychomotor and cognitive aging in four-way cross mice. Age (Dordr), 28: 265-282
[67] Shetty RA, Ikonne US, Forster MJ, Sumien N (2014). Coenzyme Q10 and alpha-tocopherol reversed age-associated functional impairments in mice. Exp Gerontol, 58: 208-218
[68] Kane DA, Anderson EJ, Price JW3rd, Woodlief TL, Lin CT, Bikman BT, et al. (2010). Metformin selectively attenuates mitochondrial H2O2 emission without affecting respiratory capacity in skeletal muscle of obese rats. Free Radic Biol Med, 49: 1082-1087
[69] Kristensen JM, Larsen S, Helge JW, Dela F, Wojtaszewski JF (2013). Two weeks of metformin treatment enhances mitochondrial respiration in skeletal muscle of AMPK kinase dead but not wild type mice. PloS one, 8: e53533
[70] Wessels B, Ciapaite J, van den Broek NM, Nicolay K, Prompers JJ (2014). Metformin impairs mitochondrial function in skeletal muscle of both lean and diabetic rats in a dose-dependent manner. PloS one, 9: e100525
[71] Zhao RR, Xu XC, Xu F, Zhang WL, Zhang WL, Liu LM, et al. (2014). Metformin protects against seizures, learning and memory impairments and oxidative damage induced by pentylenetetrazole-induced kindling in mice. Biochemical and biophysical research communications, 448: 414-417
[72] Sarkaki A, Farbood Y, Badavi M, Khalaj L, Khodagholi F, Ashabi G (2015). Metformin improves anxiety-like behaviors through AMPK-dependent regulation of autophagy following transient forebrain ischemia. Metabolic brain disease, 30: 1139-1150
[73] Audia P, Feinfeld DA, Dubrow A, Winchester JF (2008). Metformin-induced lactic acidosis and acute pancreatitis precipitated by diuretic, celecoxib, and candesartan-associated acute kidney dysfunction. Clin Toxicol (Phila), 46: 164-166
[74] Bruijstens LA, van Luin M, Buscher-Jungerhans PM, Bosch FH (2008). Reality of severe metformin-induced lactic acidosis in the absence of chronic renal impairment. Neth J Med, 66: 185-190
[75] Deutsch GA (1981). Transient blindness associated with severe diabetic ketoacidosis. Minn Med, 64: 201
[76] Feeney C, Muller M, Bryzman S, Nakada T (1998). Reversible blindness associated with alcoholic ketoacidosis: pseudomethanol intoxication. The Journal of emergency medicine, 16: 597-599
[77] Kreshak AA, Clark RF (2010). Transient vision loss in a patient with metformin-associated lactic acidosis. The American journal of emergency medicine, 28: 1059 e1055-1057
[78] Miyake T, Nishiwaki A, Yasukawa T, Ugawa S, Shimada S, Ogura Y (2013). Possible implications of acid-sensing ion channels in ischemia-induced retinal injury in rats. Jpn J Ophthalmol, 57: 120-125
[79] Ettaiche M, Deval E, Pagnotta S, Lazdunski M, Lingueglia E (2009). Acid-sensing ion channel 3 in retinal function and survival. Invest Ophthalmol Vis Sci, 50: 2417-2426
[80] Chukwunonso Obi B, Chinwuba Okoye T, Okpashi VE, Nonye Igwe C, Olisah Alumanah E (2016). Comparative Study of the Antioxidant Effects of Metformin, Glibenclamide, and Repaglinide in Alloxan-Induced Diabetic Rats. J Diabetes Res, 2016: 1635361
[81] Srividhya S, Ravichandran MK, Anuradha CV (2002). Metformin attenuates blood lipid peroxidation and potentiates antioxidant defense in high fructose-fed rats. J Biochem Mol Biol Biophys, 6: 379-385
[82] Srividhya S, Anuradha CV (2002). Metformin improves liver antioxidant potential in rats fed a high-fructose diet. Asia Pacific journal of clinical nutrition, 11: 319-322
[83] Pavlovic D, Kocic R, Kocic G, Jevtovic T, Radenkovic S, Mikic D, et al. (2000). Effect of four-week metformin treatment on plasma and erythrocyte antioxidative defense enzymes in newly diagnosed obese patients with type 2 diabetes. Diabetes, obesity & metabolism, 2: 251-256
[84] Itoh K, Chiba T, Takahashi S, Ishii T, Igarashi K, Katoh Y, et al. (1997). An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochemical and biophysical research communications, 236: 313-322
[85] Lewis KN, Wason E, Edrey YH, Kristan DM, Nevo E, Buffenstein R (2015). Regulation of Nrf2 signaling and longevity in naturally long-lived rodents. Proc Natl Acad Sci U S A, 112: 3722-3727
[86] Picone P, Nuzzo D, Caruana L, Messina E, Barera A, Vasto S, et al. (2015). Metformin increases APP expression and processing via oxidative stress, mitochondrial dysfunction and NF-kappaB activation: Use of insulin to attenuate metformin’s effect. Biochimica et biophysica acta, 1853: 1046-1059
[87] Dubey A, Forster MJ, Lal H, Sohal RS (1996). Effect of age and caloric intake on protein oxidation in different brain regions and on behavioral functions of the mouse. Arch Biochem Biophys, 333: 189-197
[88] Ingram DK, Weindruch R, Spangler EL, Freeman JR, Walford RL (1987). Dietary restriction benefits learning and motor performance of aged mice. Journal of gerontology, 42: 78-81
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