Prolonged metformin treatment leads to reduced transcription of Nrf2 and neurotrophic factors without cognitive impairment in older C57BL/6J mice

Behavioural Brain Research

Volumn 301, Issue , 2016, Pages 1-9

  Allard, Joanne S ^a,b   Perez, Evelyn J ^b   Fukui, Koji ^b,c   Carpenter, Priscilla ^a   Ingram, Donald K ^d   Cabo, Rafael de ^b  

^a HOWARD UNIVERSITY COLLEGE OF MEDICINE   (United States)

^b NATIONAL INSTITUTE ON AGING   (United States)

^c SHIBAURA INSTITUTE OF TECHNOLOGY   (Japan)

^d PENNINGTON BIOMEDICAL RESEARCH CENTER   (United States)

Author keywords

BDNF; Metformin; Neurotrophin 3; NGF; Nrf2; Water maze

Indexed keywords

BRAIN DERIVED NEUROTROPHIC FACTOR; METFORMIN; NERVE GROWTH FACTOR; NEUROTROPHIC FACTOR; NEUROTROPHIN; NEUROTROPHIN 3; TRANSCRIPTION FACTOR NRF2; ANTIDIABETIC AGENT; GLUCOSE BLOOD LEVEL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; MESSENGER RNA; NFE2L2 PROTEIN, MOUSE;

AGED; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BODY FAT; BRAIN HOMOGENATE; COGNITIVE DEFECT; CONTROLLED STUDY; DOWN REGULATION; DRUG MECHANISM; FAT INTAKE; GENE EXPRESSION REGULATION; GENETIC TRANSCRIPTION; HIPPOCAMPUS; LONG TERM CARE; MALE; MORRIS WATER MAZE TEST; MOTOR COORDINATION; MOTOR PERFORMANCE; MOUSE; NEUROPROTECTION; NONHUMAN; NRF2 GENE; PRIORITY JOURNAL; PROTEIN EXPRESSION; QUALITATIVE ANALYSIS; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; ROTAROD TEST; SPATIAL MEMORY; TREATMENT DURATION; ADIPOSE TISSUE; ADVERSE EFFECTS; AGING; ANIMAL; BRAIN; C57BL MOUSE; COGNITION; DRUG EFFECTS; GLUCOSE BLOOD LEVEL; LIPID DIET; MAZE TEST; METABOLISM; MOTOR ACTIVITY; PHYSIOLOGY; PSYCHOLOGY; RANDOMIZATION;

ADIPOSE TISSUE; AGING; AMP-ACTIVATED PROTEIN KINASES; ANIMALS; BLOOD GLUCOSE; BRAIN; BRAIN-DERIVED NEUROTROPHIC FACTOR; COGNITION; DIET, HIGH-FAT; HYPOGLYCEMIC AGENTS; MALE; MAZE LEARNING; METFORMIN; MICE, INBRED C57BL; MOTOR ACTIVITY; NERVE GROWTH FACTOR; NEUROTROPHIN 3; NF-E2-RELATED FACTOR 2; RANDOM ALLOCATION; RNA, MESSENGER;

EID: 84951266035     PISSN: 01664328     EISSN: 18727549     Source Type: Journal    
DOI: 10.1016/j.bbr.2015.12.012     Document Type: Article

References (64)

1. ID Federation IDF Diabetes Atlas 2013, International Diabetes Federation, Brussels, Belgium. ID Federation (Ed.).
2. Whiting D.R., Guariguata L., Weil C., Shaw J. IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res. Clin. Pract. 2011, 94:311-321.
3. National Diabetes Statistics Report Estimates of Diabetes and Its Burden in the United States 2014, Centers for Disease Control and Prevention, Atlanta, GA. Services USDoHaH (Ed.).
4. Moses R.G. Repaglinide/metformin fixed-dose combination to improve glycemic control in patients with type 2 diabetes: an update. Diabetes Metab. Syndr. Obes. 2010, 3:145-154.
5. Mooradian A.D., Perryman K., Fitten J., Kavonian G.D., Morley J.E. Cortical function in elderly non-insulin dependent diabetic patients. Behavioral and electrophysiologic studies. Arch. Intern. Med. 1988, 148:2369-2372.
6. Perlmuter L.C., Hakami M.K., Hodgson-Harrington C., Ginsberg J., Katz J., Singer D.E., et al. Decreased cognitive function in aging non-insulin-dependent diabetic patients. Am. J. Med. 1984, 77:1043-1048.
7. Hassenstab J.J., Sweat V., Bruehl H., Convit A. Metabolic syndrome is associated with learning and recall impairment in middle age. Dement. Geriatr. Cogn. Disord. 2010, 29:356-362.
8. Akter K., Lanza E.A., Martin S.A., Myronyuk N., Rua M., Raffa R.B. Diabetes mellitus and Alzheimer's disease: shared pathology and treatment?. Br. J. Clin. Pharmacol. 2011, 71:365-376.
9. Strachan M.W., Lawrence Lecture R.D. The brain as a target organ in Type 2 diabetes: exploring the links with cognitive impairment and dementia. Diabet. Med. 2010, 28:141-147.
10. Xu W.L., von Strauss E., Qiu C.X., Winblad B., Fratiglioni L. Uncontrolled diabetes increases the risk of Alzheimer's disease: a population-based cohort study. Diabetologia 2009, 52:1031-1039.
11. Ryan C.M., Freed M.I., Rood J.A., Cobitz A.R., Waterhouse B.R., Strachan M.W. Improving metabolic control leads to better working memory in adults with type 2 diabetes. Diabetes Care 2006, 29:345-351.
12. Beeri M.S., Schmeidler J., Silverman J.M., Gandy S., Wysocki M., Hannigan C.M., et al. Insulin in combination with other diabetes medication is associated with less Alzheimer neuropathology. Neurology 2008, 71:750-757.
13. Zhou G., Myers R., Li Y., Chen Y., Shen X., Fenyk-Melody J., et al. Role of AMP-activated protein kinase in mechanism of metformin action. J. Clin. Investig. 2001, 108:1167-1174.
14. Stephenne X., Foretz M., Taleux N., van, der Z., on G.C., Sokal E., Hue L., et al. Metformin activates AMP-activated protein kinase in primary human hepatocytes by decreasing cellular energy status. Diabetologia 2011, 54:3101-3110.
15. Bailey C.J. Metformin and intestinal glucose handling. Diabetes. Metab. Rev. 1995, 11(Suppl. 1):S23-S32.
16. Ikeda T., Iwata K., Murakami H. Inhibitory effect of metformin on intestinal glucose absorption in the perfused rat intestine. Biochem. Pharmacol. 2000, 59:887-890.
17. Hettich M.M., Matthes F., Ryan D.P., Griesche N., Schroder S., Dorn S., et al. The anti-diabetic drug metformin reduces BACE1 protein level by interfering with the MID1 complex. PloS One 2014, 9:e102420.
18. Wang J., Gallagher D., DeVito L.M., Cancino G.I., Tsui D., He L., et al. Metformin activates an atypical PKC-CBP pathway to promote neurogenesis and enhance spatial memory formation. Cell Stem Cell 2012, 11:23-35.
19. Imfeld P., Bodmer M., Jick S.S., Meier C.R. Metformin, other antidiabetic drugs, and risk of Alzheimer's disease: a population-based case-control study. J. Am. Geriatr. Soc. 2012, 60:916-921.
20. Chen Y., Zhou K., Wang R., Liu Y., Kwak Y.D., Ma T., et al. Antidiabetic drug metformin (GlucophageR) increases biogenesis of Alzheimer's amyloid peptides via up-regulating BACE1 transcription. Proc. Natl. Acad. Sci. U. S. A. 2009, 106:3907-3912.
21. Palomba S., Falbo A., La Sala G.B. Metformin and gonadotropins for ovulation induction in patients with polycystic ovary syndrome: a systematic review with meta-analysis of randomized controlled trials. Reprod. Biol. Endocrinol. 2014, 12:3.
22. Pernicova I., Korbonits M. Metformin?mode of action and clinical implications for diabetes and cancer. Nat. Rev. Endocrinol. 2014, 10:143-156.
23. Rosilio C., Ben-Sahra I., Bost F., Peyron J.F. Metformin: a metabolic disruptor and anti-diabetic drug to target human leukemia. Cancer Lett. 2014, 346:188-196.
24. Beckmann R. Absorption, distribution in the organism and elimination of metformin. Diabetologia 1969, 5:318-324.
25. Lv W.S., Wen J.P., Li L., Sun R.X., Wang J., Xian Y.X., et al. The effect of metformin on food intake and its potential role in hypothalamic regulation in obese diabetic rats. Brain Res. 2012, 1444:11-19.
26. Wilcock C., Bailey C.J. Accumulation of metformin by tissues of the normal and diabetic mouse. Xenobiotica 1994, 24:49-57.
27. Labuzek K., Suchy D., Gabryel B., Bielecka A., Liber S., Okopien B. Quantification of metformin by the HPLC method in brain regions, cerebrospinal fluid and plasma of rats treated with lipopolysaccharide. Pharmacol. Rep. 2010, 62:956-965.
28. Ashabi G., Khodagholi F., Khalaj L., Goudarzvand M., Nasiri M. Activation of AMP-activated protein kinase by metformin protects against global cerebral ischemia in male rats: interference of AMPK/PGC-1alpha pathway. Metab. Brain Dis. 2014, 29:47-58.
29. Jin Q., Cheng J., Liu Y., Wu J., Wang X., Wei S., et al. Improvement of functional recovery by chronic metformin treatment is associated with enhanced alternative activation of microglia/macrophages and increased angiogenesis and neurogenesis following experimental stroke. Brain Behav. Immun. 2014, 40:131-142.
30. Patil S.P., Jain P.D., Ghumatkar P.J., Tambe R., Sathaye S. Neuroprotective effect of metformin in MPTP-induced Parkinson's disease in mice. Neuroscience 2014, 277:747-754.
31. Zhu X.C., Jiang T., Zhang Q.Q., Cao L., Tan M.S., Wang H.F., Ding Z.Z., Tan L., Yu J.T. Chronic metformin preconditioning provides neuroprotection via suppression of nf-κb-mediated inflammatory pathway in rats with permanent cerebral ischemia. Mol. Neurobiol. 2015, 52(August (1)):375-385.
32. Aghili R., Malek M., Valojerdi A.E., Banazadeh Z., Najafi L., Khamseh M.E. Body composition in adults with newly diagnosed type 2 diabetes: effects of metformin. J. Diabetes Metab. Disord. 2014, 13:88.
33. Aubert G., Mansuy V., Voirol M.J., Pellerin L., Pralong F.P. The anorexigenic effects of metformin involve increases in hypothalamic leptin receptor expression. Metabolism 2011, 60:327-334.
34. Duan Y., Zhang R., Zhang M., Sun L., Dong S., Wang G., et al. Metformin inhibits food intake and neuropeptide Y gene expression in the hypothalamus. Neural Regen. Res. 2013, 8:2379-2388.
35. Kim H.J., Park E.Y., Oh M.J., Park S.S., Shin K.H., Choi S.H., et al. Central administration of metformin into the third ventricle of C57BL/6 mice decreases meal size and number and activates hypothalamic S6 kinase. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2013, 305:R499-R505.
36. Lee C.K., Choi Y.J., Park S.Y., Kim J.Y., Won K.C., Kim Y.W. Intracerebroventricular injection of metformin induces anorexia in rats. Diabetes Metab. J. 2012, 36:293-299.
37. Collier C.A., Bruce C.R., Smith A.C., Lopaschuk G., Dyck D.J. Metformin counters the insulin-induced suppression of fatty acid oxidation and stimulation of triacylglycerol storage in rodent skeletal muscle. Am. J. Physiol. Endocrinol. Metab. 2006, 291:E182-E189.
38. Malin S.K., Kashyap S.R. Effects of metformin on weight loss: potential mechanisms. Curr. Opin. Endocrinol. Diabetes Obes. 2014, 21:323-329.
39. Wang C., Liu F., Yuan Y., Wu J., Wang H., Zhang L., et al. Metformin suppresses lipid accumulation in skeletal muscle by promoting fatty acid oxidation. Clin. Lab. 2014, 60:887-896.
40. Martin-Montalvo A., Mercken E.M., Mitchell S.J., Palacios H.H., Mote P.L., Scheibye-Knudsen M., et al. Metformin improves healthspan and lifespan in mice. Nat. Commun. 2013, 4(2192).
41. Ratzmann K.P., Knospe S., Heinke P., Schulz B. Relationship between body fat mass, carbohydrate tolerance and IRI response during glucose infusion in subjects with early diabetes. Acta Diabetol. Lat. 1979, 16:67-75.
42. Kwankaew J., Saetung S., Chanprasertyothin S., Leelawattana R., Rattarasarn C. Lean mass inversely predicts plasma glucose levels after oral glucose load independent of insulin secretion or insulin sensitivity in glucose intolerance subjects. Endocr. J. 2014, 61:77-83.
43. Kahn S.E., Prigeon R.L., Schwartz R.S., Fujimoto W.Y., Knopp R.H., Brunzell J.D., et al. Obesity, body fat distribution, insulin sensitivity and Islet beta-cell function as explanations for metabolic diversity. J. Nutr. 2001, 131:354S-360S.
44. Rebuffe-Scrive M., Surwit R., Feinglos M., Kuhn C., Rodin J. Regional fat distribution and metabolism in a new mouse model (C57BL/6J) of non-insulin-dependent diabetes mellitus. Metab. Clin. Exp. 1993, 42:1405-1409.
45. Kane D.A., Anderson E.J., Price J.W., Woodlief T.L., Lin C.T., Bikman B.T., et al. Metformin selectively attenuates mitochondrial H2O2 emission without affecting respiratory capacity in skeletal muscle of obese rats. Free Radic. Biol. Med. 2010, 49:1082-1087.
46. Kristensen J.M., Larsen S., Helge J.W., Dela F., Wojtaszewski J.F. Two weeks of metformin treatment enhances mitochondrial respiration in skeletal muscle of AMPK kinase dead but not wild type mice. PloS One 2013, 8:e53533.
47. Andrzejewski S., Gravel S.P., Pollak M., St-Pierre J. Metformin directly acts on mitochondria to alter cellular bioenergetics. Cancer Metab. 2014, 2:12.
48. Wessels B., Ciapaite J., van, den B., roek N.M., Nicolay K., Prompers J.J. Metformin impairs mitochondrial function in skeletal muscle of both lean and diabetic rats in a dose-dependent manner. PloS One 2014, 9:e100525.
49. Alzoubi K.H., Khabour O.F., Al-Azzam S.I., Tashtoush M.H., Mhaidat N.M. Metformin Eased Cognitive Impairment Induced by Chronic l-methionine Administration: Potential Role of Oxidative Stress. Curr. Neuropharmacol. 2014, 12:186-192.
50. Zhao R.R., Xu X.C., Xu F., Zhang W.L., Zhang W.L., Liu L.M., et al. Metformin protects against seizures, learning and memory impairments and oxidative damage induced by pentylenetetrazole-induced kindling in mice. Biochem. Biophys. Res. Commun. 2014, 448:414-417.
51. Moore E.M., Mander A.G., Ames D., Kotowicz M.A., Carne R.P., Brodaty H., et al. Increased risk of cognitive impairment in patients with diabetes is associated with metformin. Diabetes Care 2013, 36:2981-2987.
52. DiTacchio K.A., Heinemann S.F., Dziewczapolski G. Metformin treatment alters memory function in a mouse model of Alzheimer's disease. J. Alzheimer's Dis. 2015, 44:43-48.
53. Berry A., Bellisario V., Capoccia S., Tirassa P., Calza A., Alleva E., et al. Social deprivation stress is a triggering factor for the emergence of anxiety- and depression-like behaviours and leads to reduced brain BDNF levels in C57BL/6 J mice. Psychoneuroendocrinology 2012, 37:762-772.
54. Bothwell M. NGF, BDNF, NT3, and NT4. Handb. Exp. Pharmacol. 2014, 220:3-15.
55. Lu B., Nagappan G., Lu Y. BDNF synaptic plasticity, cognitive function, and dysfunction. Handb. Exp. Pharmacol. 2014, 220:223-250.
56. Maier T., Guell M., Serrano L. Correlation of mRNA and protein in complex biological samples. FEBS Lett. 2009, 583:3966-3973.
57. Srividhya S., Anuradha C.V. Metformin improves liver antioxidant potential in rats fed a high-fructose diet. Asia Pac. J. Clin. Nutr. 2002, 11:319-322.
58. Esteghamati A., Eskandari D., Mirmiranpour H., Noshad S., Mousavizadeh M., Hedayati M., et al. 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. 2013, 32:179-185.
59. Formoso G., De Filippis E.A., Michetti N., Di Fulvio P., Pandolfi A., Bucciarelli T., et al. Decreased in vivo oxidative stress and decreased platelet activation following metformin treatment in newly diagnosed type 2 diabetic subjects. Diabetes Metab. Res. Rev. 2008, 24:231-237.
60. Huang H.C., Nguyen T., Pickett C.B. Phosphorylation of Nrf2 at Ser-40 by protein kinase C regulates antioxidant response element-mediated transcription. J. Biol. Chem. 2002, 277:42769-42774.
61. Lewis K.N., Wason E., Edrey Y.H., Kristan D.M., Nevo E., Buffenstein R. Regulation of Nrf2 signaling and longevity in naturally long-lived rodents. Proc. Natl. Acad. Sci. U. S. A. 2015, 112:3722-3727.
62. Picone P., Nuzzo D., Caruana L., Messina E., Barera A., Vasto S., Di Carlo M. Metformin increases APP expression and processing via oxidative stress, mitochondrial dysfunction and NF-κB activation: use of insulin to attenuate metformin's effect. Biochim. Biophys. Acta. 2015, 1853(5):1046-1059.
63. McNeilly A.D., Williamson R., Balfour D.J., Stewart C.A., Sutherland C. A high-fat-diet-induced cognitive deficit in rats that is not prevented by improving insulin sensitivity with metformin. Diabetologia 2012, 55:3061-3070.
64. Anisimov V.N., Berstein L.M., Popovich I.G., Zabezhinski M.A., Egormin P.A., Piskunova T.S., et al. If started early in life, metformin treatment increases life span and postpones tumors in female SHR mice. Aging (Albany NY) 2011, 3:148-157.