The GLP-1 receptor agonist liraglutide reduces pathology-specific tau phosphorylation and improves motor function in a transgenic hTauP301L mouse model of tauopathy

Brain Research

Volumn 1634, Issue , 2016, Pages 158-170

  Hansen, Henrik H ^a   Barkholt, Pernille ^a   Fabricius, Katrine ^a   Jelsing, Jacob ^a   Terwel, Dick ^b   Pyke, Charles ^c   Knudsen, Lotte Bjerre ^c   Vrang, Niels ^a  

^a Gubra   (Denmark)

^b NV reMYND   (Belgium)

^c NOVO NORDISK A S   (Denmark)

Author keywords

Alzheimer's disease; GLP 1 receptor agonist; hTauP301L transgenic mouse; Liraglutide; Phosphorylated tau; Tauopathy

Indexed keywords

LIRAGLUTIDE; TAU PROTEIN; GLUCAGON LIKE PEPTIDE 1 RECEPTOR; MAPT PROTEIN, HUMAN; NEUROPROTECTIVE AGENT;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DISEASE SEVERITY; EXPERIMENTAL MODEL; FEMALE; HINDLIMB; LETHALITY; MOTOR PERFORMANCE; MOUSE; NEUROFIBRILLARY TANGLE; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; SURVIVAL RATE; TAUOPATHY; WILD TYPE; AGONISTS; ANIMAL; BLOOD; BODY WEIGHT; BRAIN; CONVALESCENCE; DISEASE MODEL; DRUG EFFECTS; EATING; GENETICS; METABOLISM; MOTOR ACTIVITY; NERVE CELL; PATHOPHYSIOLOGY; PHOSPHORYLATION; SURVIVAL ANALYSIS; TRANSGENIC MOUSE;

ANIMALS; BODY WEIGHT; BRAIN; DISEASE MODELS, ANIMAL; EATING; FEMALE; GLUCAGON-LIKE PEPTIDE-1 RECEPTOR; LIRAGLUTIDE; MICE; MICE, TRANSGENIC; MOTOR ACTIVITY; NEURONS; NEUROPROTECTIVE AGENTS; PHOSPHORYLATION; RECOVERY OF FUNCTION; SURVIVAL ANALYSIS; TAU PROTEINS; TAUOPATHIES;

EID: 84962229876     PISSN: 00068993     EISSN: 18726240     Source Type: Journal    
DOI: 10.1016/j.brainres.2015.12.052     Document Type: Article

References (76)

1. P.A. Adlard, and B.J. Cummings Alzheimer's disease - A sum greater than its parts? Neurobiol. Aging 25 2004 743 746
2. H. Agerso, L.B. Jensen, B. Elbrond, P. Rolan, and M. Zdravkovic The pharmacokinetics, pharmacodynamics, safety and tolerability of NN2211, a new long-acting GLP-1 derivative, in healthy men Diabetologia 45 2002 195 202
3. B. Allen, E. Ingram, M. Takao, M.J. Smith, R. Jakes, K. Virdee, H. Yoshida, M. Holzer, M. Craxton, P.C. Emson, C. Atzori, A. Migheli, R.A. Crowther, B. Ghetti, M.G. Spillantini, and M. Goedert Abundant tau filaments and nonapoptotic neurodegeneration in transgenic mice expressing human P301S tau protein J. Neurosci. 22 2002 9340 9351
4. Ad.C. Alonso, A. Mederlyova, M. Novak, I. Grundke-Iqbal, and K. Iqbal Promotion of hyperphosphorylation by frontotemporal dementia tau mutations J. Biol. Chem. 279 2004 34873 34881
5. E. Alvarez, M.D. Martínez, I. Roncero, J.A. Chowen, B. García-Cuartero, J.D. Gispert, C. Sanz, P. Vázquez, A. Maldonado, J. de Cáceres, M. Desco, M.A. Pozo, and E. Blázquez The expression of GLP-1 receptor mRNA and protein allows the effect of GLP-1 on glucose metabolism in the human hypothalamus and brainstem J. Neurochem. 92 2005 798 806
6. E. Alvarez, I. Roncero, J.A. Chowen, B. Thorens, and E. Blázquez Expression of the glucagon-like peptide-1 receptor gene in rat brain J. Neurochem. 66 1996 920 927
7. E.-D. Baraboi, D.H. St-Pierre, J. Shooner, E. Timofeeva, and D. Richard Brain activation following peripheral administration of the GLP-1 receptor agonist exendin-4 Am. J. Physiol. Regul. Integr. Comp. Physiol. 301 2011 R1011 R1024
8. F. Bassil, P.-O. Fernagut, E. Bezard, and W.G. Meissner Insulin, IGF-1 and GLP-1 signaling in neurodegenerative disorders: Targets for disease modification? Prog. Neurobiol. 118 2014 1 18
9. G. Bertilsson, C. Patrone, O. Zachrisson, A. Andersson, K. Dannaeus, J. Heidrich, J. Kortesmaa, A. Mercer, E. Nielsen, H. Rönnholm, and L. Wikström Peptide hormone exendin-4 stimulates subventricular zone neurogenesis in the adult rodent brain and induces recovery in an animal model of Parkinson's disease J. Neurosci. Res. 86 2008 326 338
10. G.J. Biessels, S. Staekenborg, E. Brunner, C. Brayne, and P. Scheltens Risk of dementia in diabetes mellitus: A systematic review Lancet Neurol. 5 2006 64 74
11. K. Boekhoorn, D. Terwel, B. Biemans, P. Borghgraef, O. Wiegert, G.J.A. Ramakers, K. de Vos, H. Krugers, T. Tomiyama, H. Mori, M. Joels, F. van Leuven, and P.J. Lucassen Improved long-term potentiation and memory in young tau-P301L transgenic mice before onset of hyperphosphorylation and tauopathy J. Neurosci. 26 2006 3514 3523
12. M. Bomba, D. Ciavardelli, E. Silvestri, L.M.T. Canzoniero, R. Lattanzio, P. Chiappini, M. Piantelli, C. Di Ilio, A. Consoli, and S.L. Sensi Exenatide promotes cognitive enhancement and positive brain metabolic changes in PS1-KI mice but has no effects in 3xTg-AD animals Cell Death Dis. 4 2013 e612
13. P. Borghgraef, C. Menuet, C. Theunis, J.V. Louis, H. Devijver, H. Maurin, C. Smet-Nocca, G. Lippens, G. Hilaire, H. Gijsen, D. Moechars, and F. Van Leuven Increasing brain protein O-GlcNAc-ylation mitigates breathing defects and mortality of Tau.P301L mice PLoS One 8 2013 e84442
14. H.Y. Cai, C. Hölscher, X.H. Yue, S.X. Zhang, X.H. Wang, F. Qiao, W. Yang, and J.S. Qi Lixisenatide rescues spatial memory and synaptic plasticity from amyloid β protein-induced impairments in rats Neuroscience 277 2014 6 13
15. S. Chen, F.M. An, L. Yin, A.R. Liu, D.K. Yin, W.B. Yao, and X.D. Gao Glucagon-like peptide-1 protects hippocampal neurons against advanced glycation end product-induced tau hyperphosphorylation Neuroscience 256 2014 137 146
16. S. Chen, A.-r Liu, F.-m An, W.-b Yao, and X.-d Gao Amelioration of neurodegenerative changes in cellular and rat models of diabetes-related Alzheimer's disease by exendin-4 Age 34 2012 1211 1224
17. Z. Chen, and C. Zhong Decoding Alzheimer's disease from perturbed cerebral glucose metabolism: Implications for diagnostic and therapeutic strategies Prog. Neurobiol. 108 2013 21 43
18. N. Crespo-Biel, C. Theunis, P. Borghgraef, B. Lechat, H. Devijver, H. Maurin, and F. Van Leuven Phosphorylation of protein Tau by GSK3β prolongs survival of bigenic Tau.P301L×GSK3β mice by delaying brainstem tauopathy Neurobiol. Dis. 67 2014 119 132
19. N. Crespo-Biel, C. Theunis, and F. Van Leuven Protein tau: Prime cause of synaptic and neuronal degeneration in Alzheimer's disease Int. J. Alzheimers Dis. 2012 2012 1 13
20. B. DellaValle, C. Hempel, F.F. Johansen, and J.A.L. Kurtzhals GLP-1 improves neuropathology after murine cold lesion brain trauma Ann. Clin. Transl. Neurol. 1 2014 721 732
21. M. Dutschmann, C. Menuet, G.M. Stettner, C. Gestreau, P. Borghgraef, H. Devijver, L. Gielis, G. Hilaire, and F. Van Leuven Upper airway dysfunction of Tau-P301L mice correlates with tauopathy in midbrain and ponto-medullary brainstem nuclei J. Neurosci. 30 2010 1810 1821
22. V.A. Gault, and C. Hölscher GLP-1 agonists facilitate hippocampal LTP and reverse the impairment of LTP induced by beta-amyloid Eur. J. Pharmacol. 587 2008 112 117
23. M. Gejl, J. Rungby, B. Brock, and A. Gjedde At the centennial of Michaelis and Menten, competing Michaelis-Menten steps explain effect of GLP-1 on blood-brain transfer and metabolism of glucose Basic Clin. Pharmacol. Toxicol. 115 2014 162 171
24. M. Goedert, R.A. Crowther, and M.G. Spillantini Tau mutations cause frontotemporal dementias Neuron 21 1998 955 958
25. G. Gu, B. Roland, K. Tomaselli, C.S. Dolman, C. Lowe, and J.S. Heilig Glucagon-like peptide-1 in the rat brain: Distribution of expression and functional implication J. Comp. Neurol. 521 2013 2235 2261
26. H.J. Gundersen, P. Bagger, T.F. Bendtsen, S.M. Evans, L. Korbo, N. Marcussen, A. Møller, K. Nielsen, J.R. Nyengaard, and B. Pakkenberg The new stereological tools: Disector, fractionator, nucleator and point sampled intercepts and their use in pathological research and diagnosis APMIS 96 1988 857 881
27. H.J. Gundersen, and E.B. Jensen The efficiency of systematic sampling in stereology and its prediction J. Microsc. 147 1987 229 263
28. R. Göke, P.J. Larsen, J.D. Mikkelsen, and S.P. Sheikh Distribution of GLP-1 binding sites in the rat brain: Evidence that exendin-4 is a ligand of brain GLP-1 binding sites Eur. J. Neurosci. 7 1995 2294 3000
29. A. Hamilton, S. Patterson, D. Porter, V.A. Gault, and C. Holscher Novel GLP-1 mimetics developed to treat type 2 diabetes promote progenitor cell proliferation in the brain J. Neurosci. Res. 89 2011 481 489
30. J. Hardy, and D.J. Selkoe The amyloid hypothesis of Alzheimer's disease: Progress and problems on the road to therapeutics Science 297 2002 353 356
31. C. Holscher Potential role of glucagon-like peptide-1 (GLP-1) in neuroprotection CNS Drugs 26 2012 871 882
32. J.J. Holst The physiology of glucagon-like peptide 1 Physiol. Rev. 87 2007 1409 1439
33. D.M. Holtzman, J.C. Morris, and A.M. Goate Alzheimer's disease: The challenge of the second century Sci. Transl. Med. 3 2011
34. M. Hong, V. Zhukareva, V. Vogelsberg-Ragaglia, Z. Wszolek, L. Reed, B.I. Miller, D.H. Geschwind, T.D. Bird, D. McKeel, A. Goate, J.C. Morris, K.C. Wilhelmsen, G.D. Schellenberg, J.Q. Trojanowski, and V.M. Lee Mutation-specific functional impairments in distinct tau isoforms of hereditary FTDP-17 Science 282 1998 1914 1917
35. T.M. Hsu, J.D. Hahn, V.R. Konanur, A. Lam, and S.E. Kanoski Hippocampal GLP-1 receptors influence food intake, meal size, and effort-based responding for food through volume transmission Neuropsychopharmacology 40 2015 327 337
36. T. Jaworski, I. Dewachter, C.M. Seymour, P. Borghgraef, H. Devijver, S. Kügler, and F. Van Leuven Alzheimer's disease: Old problem, new views from transgenic and viral models Biochim. Biophys. Acta 1802 2010 808 818
37. Y.D. Ke, F. Delerue, A. Gladbach, J. Götz, and L.M. Ittner Experimental diabetes mellitus exacerbates tau pathology in a transgenic mouse model of Alzheimer's disease PLoS One 4 2009 e7917
38. A. Kremer, H. Maurin, D. Demedts, H. Devijver, P. Borghgraef, and F. Van Leuven Early improved and late defective cognition is reflected by dendritic spines in Tau.P301L mice J. Neurosci. 31 2011 18036 18047
39. M. Küchler, K. Fouad, O. Weinmann, M.E. Schwab, and O. Raineteau Red nucleus projections to distinct motor neuron pools in the rat spinal cord J. Comp. Neurol. 448 2002 349 359
40. J. Lewis, E. McGowan, J. Rockwood, H. Melrose, P. Nacharaju, M. Van Slegtenhorst, K. Gwinn-Hardy, M. Paul Murphy, M. Baker, X. Yu, K. Duff, J. Hardy, A. Corral, W.L. Lin, S.H. Yen, D.W. Dickson, P. Davies, and M. Hutton Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein Nat. Genet. 25 2000 402 405
41. L. Li, Z.-F. Zhang, C. Holscher, C. Gao, Y.-H. Jiang, and Y.-Z. Liu (Val8) glucagon-like peptide-1 prevents tau hyperphosphorylation, impairment of spatial learning and ultra-structural cellular damage induced by streptozotocin in rat brains Eur. J. Pharmacol. 674 2012 280 286
42. Y. Li, K.B. Duffy, M.A. Ottinger, B. Ray, J.A. Bailey, H.W. Holloway, D. Tweedie, T. Perry, M.P. Mattson, D. Kapogiannis, K. Sambamurti, D.K. Lahiri, and N.H. Greig GLP-1 receptor stimulation reduces amyloid-beta peptide accumulation and cytotoxicity in cellular and animal models of Alzheimer's disease J. Alzheimers Dis. 19 2010 1205 1219
43. Y. Li, D. Tweedie, M.P. Mattson, H.W. Holloway, and N.H. Greig Enhancing the GLP-1 receptor signaling pathway leads to proliferation and neuroprotection in human neuroblastoma cells J. Neurochem. 113 2010 1621 1631
44. D.L. Ma, F.Q. Chen, W.J. Xu, W.Z. Yue, G. Yuan, and Y. Yang Early intervention with glucagon-like peptide 1 analog liraglutide prevents tau hyperphosphorylation in diabetic db/db mice J. Neurochem. 135 2015 301 308
45. C.M. Mack, C.X. Moore, C.M. Jodka, S. Bhavsar, J.K. Wilson, J.A. Hoyt, J.L. Roan, C. Vu, K.D. Laugero, D.G. Parkes, and A.A. Young Antiobesity action of peripheral exenatide (exendin-4) in rodents: Effects on food intake, body weight, metabolic status and side-effect measures Int. J. Obes. 30 2006 1332 1340
46. H. Maurin, S.-A. Chong, I. Kraev, H. Davies, A. Kremer, C.M. Seymour, B. Lechat, T. Jaworski, P. Borghgraef, H. Devijver, G. Callewaert, M.G. Stewart, and F. Van Leuven Early structural and functional defects in synapses and myelinated axons in stratum lacunosum moleculare in two preclinical models for tauopathy PLoS One 9 2014 e87605
47. P.L. McClean, and C. Hölscher Liraglutide can reverse memory impairment, synaptic loss and reduce plaque load in aged APP/PS1 mice, a model of Alzheimer's disease Neuropharmacology 76 pt.A 2014 57 67
48. P.L. McClean, and C. Hölscher Lixisenatide, a drug developed to treat type 2 diabetes, shows neuroprotective effects in a mouse model of Alzheimer's disease Neuropharmacology 86C 2014 241 258
49. P.L. McClean, V. Parthsarathy, E. Faivre, and C. Hölscher The diabetes drug liraglutide prevents degenerative processes in a mouse model of Alzheimer's disease J. Neurosci. 31 2011 6587 6594
50. J.J. Meier GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus Nat. Rev. Endocrinol. 8 2012 728 742
51. C. Menuet, P. Borghgraef, N. Voituron, C. Gestreau, L. Gielis, H. Devijver, M. Dutschmann, F. Van Leuven, and G. Hilaire Isoflurane anesthesia precipitates tauopathy and upper airways dysfunction in pre-symptomatic Tau.P301L mice: Possible implication for neurodegenerative diseases Neurobiol. Dis. 46 2012 234 243
52. I. Merchenthaler, M. Lane, and P. Shughrue Distribution of pre-pro-glucagon and glucagon-like peptide-1 receptor messenger RNAs in the rat central nervous system J. Comp. Neurol. 403 1999 261 280
53. L.H. Nilsen, C. Rae, L.M. Ittner, J. Götz, and U. Sonnewald Glutamate metabolism is impaired in transgenic mice with tau hyperphosphorylation J. Cereb. Blood Flow Metab. 33 2013 684 691
54. C. Orskov, S.S. Poulsen, M. Møller, and J.J. Holst Glucagon-like peptide I receptors in the subfornical organ and the area postrema are accessible to circulating glucagon-like peptide I Diabetes 45 1996 832 835
55. V. Parthsarathy, and C. Hölscher Chronic treatment with the GLP1 analogue liraglutide increases cell proliferation and differentiation into neurons in an AD mouse model PLoS One 8 2013 e58784
56. T. Perry, D.K. Lahiri, K. Sambamurti, D. Chen, M.P. Mattson, J.M. Egan, and N.H. Greig Glucagon-like peptide-1 decreases endogenous amyloid-beta peptide (Abeta) levels and protects hippocampal neurons from death induced by Abeta and iron J. Neurosci. Res. 72 2003 603 612
57. C.J. Price, T.D. Hoyda, and A.V. Ferguson The area postrema: A brain monitor and integrator of systemic autonomic state Neuroscientist 14 2008 182 194
58. P.L. Pugh, S.F. Ahmed, M.I. Smith, N. Upton, and A.J. Hunter A behavioural characterisation of the FVB/N mouse strain Behav. Brain Res. 155 2004 283 289
59. H.W. Querfurth, and F.M. LaFerla Alzheimer's disease N. Engl. J. Med. 362 2010 329 344
60. C. Reitz, and R. Mayeux Alzheimer disease: Epidemiology, diagnostic criteria, risk factors and biomarkers Biochem. Pharmacol. 88 2014 640 651
61. P. Richards, H.E. Parker, A.E. Adriaenssens, J.M. Hodgson, S.C. Cork, S. Trapp, F.M. Gribble, and F. Reimann Identification and characterization of GLP-1 receptor-expressing cells using a new transgenic mouse model Diabetes 63 2014 1224 1233
62. U. Rüb, K. Del Tredici, C. Schultz, D.R. Thal, E. Braak, and H. Braak The autonomic higher order processing nuclei of the lower brain stem are among the early targets of the Alzheimer's disease-related cytoskeletal pathology Acta Neuropathol. 101 2001 555 564
63. N. Scarmeas, G.M. Hadjigeorgiou, A. Papadimitriou, B. Dubois, M. Sarazin, J. Brandt, M. Albert, K. Marder, K. Bell, L.S. Honig, D. Wegesin, and Y. Stern Motor signs during the course of Alzheimer disease Neurology 63 2004 975 982
64. A. Secher, J. Jelsing, A.F. Baquero, J. Hecksher-Sørensen, M.A. Cowley, L.S. Dalbøge, G. Hansen, K.L. Grove, C. Pyke, K. Raun, L. Schäffer, M. Tang-Christensen, S. Verma, B.M. Witgen, N. Vrang, and L.B. Knudsen The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss J. Clin. Investig. 124 2014 4473 4488
65. A. Serrano-Pozo, M.P. Frosch, E. Masliah, and B.T. Hyman Neuropathological Alterations in Alzheimer Disease. Cold Spring Harb Perspect. Med. 1 2011 a006189
66. S. Sisley, R. Gutierrez-Aguilar, M. Scott, D.A. D'Alessio, D.A. Sandoval, and R.J. Seeley Neuronal GLP1R mediates liraglutide's anorectic but not glucose-lowering effect J. Clin. Investig. 124 2014 2456 2463
67. A. Spolcova, B. Mikulaskova, M. Holubova, V. Nagelova, Z. Pirnik, J. Zemenova, M. Haluzik, B. Zelezna, M.C. Galas, and L. Maletinska Anorexigenic lipopeptides ameliorate central insulin signaling and attenuate tau phosphorylation in hippocampi of mice with monosodium glutamate-induced obesity J. Alzheimers Dis. 45 2015 823 835
68. H.H. Subramanian, and G. Holstege The midbrain periaqueductal gray changes the eupneic respiratory rhythm into a breathing pattern necessary for survival of the individual and of the species Prog. Brain Res. 212 2014 351 384
69. K. Talbot, and H.-Y. Wang The nature, significance, and glucagon-like peptide-1 analog treatment of brain insulin resistance in Alzheimer's disease Alzheimers Dement. 10 2014 S12 S25
70. K. Tatarkiewicz, E.J. Sablan, C.J. Polizzi, C. Villescaz, and D.G. Parkes Long-term metabolic benefits of exenatide in mice are mediated solely via the known glucagon-like peptide 1 receptor Am. J. Physiol. Regul. Integr. Comp. Physiol. 306 2014 R490 R498
71. D. Terwel, R. Lasrado, J. Snauwaert, E. Vandeweert, C. Van Haesendonck, P. Borghgraef, and F. Van Leuven Changed conformation of mutant Tau-P301L underlies the moribund tauopathy, absent in progressive, nonlethal axonopathy of Tau-4R/2N transgenic mice J. Biol. Chem. 280 2005 3963 3973
72. D. Terwel, D. Muyllaert, I. Dewachter, P. Borghgraef, S. Croes, H. Devijver, and F. Van Leuven Amyloid activates GSK-3beta to aggravate neuronal tauopathy in bigenic mice Am. J. Pathol. 172 2008 786 798
73. N.T. Vagelatos, and G.D. Eslick Type 2 Diabetes as a risk factor for Alzheimer's disease: The confounders, interactions, and neuropathology associated with this relationship Epidemiol. Rev. 35 2013 152 160
74. W. Xu, Y. Yang, G. Yuan, W. Zhu, D. Ma, and S. Hu Exendin-4, a glucagon-like peptide-1 receptor agonist, reduces Alzheimer disease-associated tau hyperphosphorylation in the hippocampus of rats with type 2 diabetes J. Investig. Med.: Off. Publ. Am. Fed. Clin. Res. 63 2015 267 272
75. H. Yamamoto, C.E. Lee, J.N. Marcus, T.D. Williams, J.M. Overton, M.E. Lopez, A.N. Hollenberg, L. Baggio, C.B. Saper, D.J. Drucker, and J.K. Elmquist Glucagon-like peptide-1 receptor stimulation increases blood pressure and heart rate and activates autonomic regulatory neurons J. Clin. Investig. 110 2002 43 52
76. Y. Yang, J. Zhang, D. Ma, M. Zhang, S. Hu, S. Shao, and C.-X. Gong Subcutaneous administration of liraglutide ameliorates Alzheimer-associated tau hyperphosphorylation in rats with type 2 diabetes J. Alzheimers Dis. 37 2013 637 648