CHF5074 and LY450139 sub-acute treatments differently affect cortical extracellular glutamate levels in pre-plaque Tg2576 mice

Neuroscience

Volumn 266, Issue , 2014, Pages 13-22

  Beggiato, S ^a   Giuliani, A ^b   Sivilia, S ^b   Lorenzini, L ^b   Antonelli, T ^a,c   Imbimbo, B P ^d   Giardino, L ^b,c   Calza L ^b,c   Ferraro, L ^a,c  

^a UNIVERSITY OF FERRARA   (Italy)

^b UNIVERSITY OF BOLOGNA   (Italy)

^c IRET Foundation   (Italy)

^d Research and Development   (Italy)

Author keywords

amyloid targeting drugs; secretase; Alzheimer's disease; In vivo microdialysis; Novel object recognition and contextual fear conditioning

Indexed keywords

AMYLOID BETA PROTEIN; CHF 5074; GLUTAMIC ACID; NONSTEROID ANTIINFLAMMATORY AGENT; SEMAGACESTAT; UNCLASSIFIED DRUG; 1-(3',4'-DICHLORO-2-FLUORO(1,1'-BIPHENYL)-4-YL)CYCLOPROPANECARBOXYLIC ACID; ALANINE; AZEPINE DERIVATIVE; CYCLOPROPANE DERIVATIVE; FLURBIPROFEN; N2-((2S)-2-(3,5-DIFLUOROPHENYL)-2-HYDROXYETHANOYL)-N1-((7S)-5-METHYL-6-OXO-6,7-DIHYDRO-5H-DIBENZO(B,D)AZEPIN-7-YL)-L-ALANINAMIDE; NEUROPROTECTIVE AGENT;

ACUTE DRUG ADMINISTRATION; ALZHEIMER DISEASE; AMNESIA; AMYLOID PLAQUE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; COGNITIVE DEFECT; CONTROLLED STUDY; DIALYSATE; DRUG EFFECT; EXTRACELLULAR MATRIX; FEMALE; IN VIVO STUDY; MEMORY DISORDER; MOUSE; NEUROTRANSMISSION; NONHUMAN; PREFRONTAL CORTEX; PRIORITY JOURNAL; PROTEIN SYNTHESIS; TG2576 MOUSE; ANALOGS AND DERIVATIVES; ANIMAL; CHEMISTRY; DISEASE MODEL; DRUG EFFECTS; EXTRACELLULAR SPACE; HUMAN; METABOLISM; MICRODIALYSIS; SYNAPTIC TRANSMISSION; TRANSGENIC MOUSE;

ALANINE; ALZHEIMER DISEASE; ANIMALS; AZEPINES; CYCLOPROPANES; DISEASE MODELS, ANIMAL; EXTRACELLULAR SPACE; FEMALE; FLURBIPROFEN; GLUTAMIC ACID; HUMANS; MICE; MICE, TRANSGENIC; MICRODIALYSIS; NEUROPROTECTIVE AGENTS; PREFRONTAL CORTEX; SYNAPTIC TRANSMISSION;

EID: 84896857547     PISSN: 03064522     EISSN: 18737544     Source Type: Journal    
DOI: 10.1016/j.neuroscience.2014.01.065     Document Type: Article

References (63)

1. Alberdi E., Sánchez-Gómez M.V., Cavaliere F., Pérez-Samartín A., Zugaza J.L., Trullas R., Domercq M., Matute C. Amyloid beta oligomers induce Ca2+ dysregulation and neuronal death through activation of ionotropic glutamate receptors. Cell Calcium 2010, 47:264-272.
2. Ardiles A.-O., Tapia-Rojas C.-C., Mandal M., Alexandre F., Kirkwood A., Inestrosa N.-C., Palacios A.-G. Postsynaptic dysfunction is associated with spatial and object recognition memory loss in a natural model of Alzheimer's disease. Proc Natl Acad Sci U S A 2012, 109:13835-13840.
3. Arendt T. Synaptic degeneration in Alzheimer's disease. Acta Neuropathol 2009, 118:167-179.
4. Ashe K.-H., Zahs K.-R. Probing the biology of Alzheimer's disease in mice. Neuron 2010, 66:631-645.
5. Balducci C., Mehdawy B., Mare L., Giuliani A., Lorenzini L., Sivilia S., Giardino L., Calzà L., Lanzillotta A., Sarnico I., Pizzi M., Usiello A., Viscomi A.-R., Ottonello S., Villetti G., Imbimbo B.-P., Nisticò G., Forloni G., Nisticò R. The γ-secretase modulator CHF5074 restores memory and hippocampal synaptic plasticity in plaque-free Tg2576 mice. J Alzheimers Dis 2011, 24:799-816.
6. Barnes C.-A., Danysz W., Parsons C.G. Effects of the uncompetitive NMDA receptor antagonist memantine on hippocampal long-term potentiation, short-term exploratory modulation and spatial memory in awake, freely moving rats. Eur J Neurosci 1996, 8:565-571.
7. Bear M.F. A synaptic basis for memory storage in the cerebral cortex. Proc Natl Acad Sci U S A 1996, 93:13453-13459.
8. Bieschke J., Herbst M., Wiglenda T., Friedrich R.P., Boeddrich A., Schiele F., Kleckers D., Lopez del Amo J.M., Grüning B.A., Wang Q., Schmidt M.R., Lurz R., Anwyl R., Schnoegl S., Fändrich M., Frank R.F., Reif B., Günther S., Walsh D.M., Wanker E.E. Small-molecule conversion of toxic oligomers to nontoxic β-sheet-rich amyloid fibrils. Nat Chem Biol 2011, 8:93-101.
9. Canas P.M., Simões A.P., Rodrigues R.J., Cunha R.A. Predominant loss of glutamatergic terminal markers in a β-amyloid peptide model of Alzheimer's disease. Neuropharmacology 2014, 76(Pt A):51-56.
10. Chen K.-H., Reese E.-A., Kim H.-W., Rapoport S.-I., Rao J.-S. Disturbed neurotransmitter transporter expression in Alzheimer's disease brain. J Alzheimers Dis 2011, 26:755-766.
11. Cheng S., Li L., He S., Liu J., Sun Y., He M., Grasing K., Premont R.-T., Suo W.-Z. GRK5 deficiency accelerates {beta}-amyloid accumulation in Tg2576 mice via impaired cholinergic activity. J Biol Chem 2010, 285:41541-41548.
12. Christensen D.-Z., Kraus S.-L., Flohr A., Cotel M.-C., Wirths O., Bayer T.-A. Transient intraneuronal A beta rather than extracellular plaque pathology correlates with neuron loss in the frontal cortex of APP/PS1KI mice. Acta Neuropathol 2008, 116:647-655.
13. Comery T.-A., Martone R.-L., Aschmies S., Atchison K.-P., Diamantidis G., Gong X., Zhou H., Kreft A.-F., Pangalos M.-N., Sonnenberg-Reines J., Jacobsen J.-S., Marquis K.-L. Acute gamma-secretase inhibition improves contextual fear conditioning in the Tg2576 mouse model of Alzheimer's disease. J Neurosci 2005, 25:8898-8902.
14. Danysz W., Parsons C.-G. Alzheimer's disease, b-amyloid, glutamate, NMDA receptors and memantine-searching for the connections. Br J Pharmacol 2012, 167:324-352.
15. Del Arco A., Mora F. Glutamate-dopamine in vivo interaction in the prefrontal cortex modulates the release of dopamine and acetylcholine in the nucleus accumbens of the awake rat. J Neural Transm 2005, 112:97-109.
16. Di Santo S.-G., Prinelli F., Adorni F., Caltagirone C., Musicco M. A meta-analysis of the efficacy of donepezil, rivastigmine, galantamine, and memantine in relation to severity of Alzheimer's disease. J Alzheimers Dis 2013, 35:349-361.
17. Doody R.S., Raman R., Farlow M., Iwatsubo T., Vellas B., Joffe S., Kieburtz K., He F., Sun X., Thomas R.G., Aisen P.S., Siemers E., Sethuraman G., Mohs R. A phase 3 trial of semagacestat for treatment of Alzheimer's disease. N Engl J Med 2013, 369:341-350. Alzheimer's Disease Cooperative Study Steering Committee, Semagacestat Study GroupSemagacestat Study Group.
18. Giannakopoulos P., Herrmann F.-R., Bussière T., Bouras C., Kövari E., Perl D.-P., Morrison J.-H., Gold G., Hof P.-R. Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer's disease. Neurology 2003, 60:1495-1500.
19. Giannakopoulos P., Kövari E., Gold G., von Gunten A., Hof P.-R., Bouras C. Pathological substrates of cognitive decline in Alzheimer's disease. Front Neurol Neurosci 2009, 24:20-29.
20. Giuliani A., Beggiato S., Baldassarro V.A., Mangano C., Giardino L., Imbimbo B.-P., Antonelli T., Calzà L., Ferraro L. CHF5074 restores visual memory ability and pre-synaptic cortical acetylcholine release in pre-plaque Tg2576 mice. J Neurochem 2013, 124:613-620.
21. Henley D.-B., May P.-C., Dean R.-A., Siemers E.-R. Development of semagacestat (LY450139), a functional gamma-secretase inhibitor, for the treatment of Alzheimer's disease. Expert Opin Pharmacother 2009, 10:1657-1664.
22. Hermann D., Both M., Ebert U., Gross G., Schoemaker H., Draguhn A., Wicke K., Nimmrich V. Synaptic transmission is impaired prior to plaque formation in amyloid precursor protein-overexpressing mice without altering behaviorally-correlated sharp wave-ripple complexes. Neuroscience 2009, 162:1081-1090.
23. Hermann D., Mezler M., Müller M.K., Wicke K., Gross G., Draguhn A., Bruehl C., Nimmrich V. Synthetic Aβ oligomers (Aβ(1-42) globulomer) modulate presynaptic calcium currents: prevention of Aβ-induced synaptic deficits by calcium channel blockers. Eur J Pharmacol 2013, 702:44-55.
24. Hoxha E., Boda E., Montarolo F., Parolisi R., Tempia F. Excitability and synaptic alterations in the cerebellum of APP/PS1 mice. PLoS One 2012, 7:e34726.
25. Hsiao K., Chapman P., Nilsen S., Eckman C., Harigaya Y., Younkin S., Yang F., Cole G. Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science 1996, 274:99-102.
26. Hyman B.-T. Amyloid-dependent and amyloid-independent stages of Alzheimer disease. Arch Neurol 2011, 68:1062-1064.
27. Imbimbo B.-P., Del Giudice E., Colavito D., D'Arrigo A., Dalle Carbonare M., Villetti G., Facchinetti F., Volta R., Pietrini V., Baroc M.-F., Serneels L., De Strooper B., Leon A. 1-(3',4'-Dichloro-2-fluoro[1,1'-biphenyl]-4-yl)-cyclopropanecarboxylic acid (CHF5074), a novel gamma-secretase modulator, reduces brain beta-amyloid pathology in a transgenic mouse model of Alzheimer's disease without causing peripheral toxicity. J Pharmacol Exp Ther 2007, 323:822-830.
28. Imbimbo B.-P., Hutter-Paier B., Villetti G., Facchinetti F., Cenacchi V., Volta R., Lanzillotta A., Pizzi M., Windisch M. CHF5074, a novel gamma-secretase modulator, attenuates brain beta-amyloid pathology and learning deficit in a mouse model of Alzheimer's disease. Br J Pharmacol 2009, 156:982-993.
29. Imbimbo B.-P., Giardino L., Sivilia S., Giuliani A., Gusciglio M., Pietrini V., Del Giudice E., D'Arrigo A., Leon A., Villetti G., Calzà L. CHF5074, a novel gamma-secretase modulator, restores hippocampal neurogenesis potential and reverses contextual memory deficit in a transgenic mouse model of Alzheimer's disease. J Alzheimers Dis 2010, 20:159-173.
30. Imbimbo B.-P., Frigerio E., Breda M., Fiorentini F., Fernandez M., Sivilia S., Giardino L., Calzà L., Norris D., Casula D., Shenouda M. Pharmacokinetics and pharmacodynamics of CHF5074 After short-term administration in healthy subjects. Alzheimer Dis Assoc Disord 2013, 27:278-286.
31. Karreman M., Moghaddam B. Effect of a pharmacological stressor on glutamate efflux in the prefrontal cortex. Brain Res 1996, 716:180-182.
32. Lanzillotta A, Porrini V, Branca C, Benarese M, Imbimbo BP, Pizzi M (2013) CHF5074. In: clinical development for the treatment and prevention of Alzheimer's disease, switches cultured microglia from M1 to M2 activation state. The 11th International Conference on Alzheimer's & Parkinson's Diseases, Florence, March 6-10.
33. Lesné S., Koh M.-T., Kotilinek L., Kayed R., Glabe C.-G., Yang A., Gallagher M., Ashe K.-H. A specific amyloid-beta protein assembly in the brain impairs memory. Nature 2006, 440:352-357.
34. Lue L.-F., Kuo Y.-M., Roher A.-E., Brachova L., Shen Y., Sue L., Beach T., Kurth J.-H., Rydel R.-E., Rogers J. Soluble amyloid beta peptide concentration as a predictor of synaptic change in Alzheimer's disease. Am J Pathol 1999, 155:853-862.
35. Mangialasche F., Solomon A., Winblad B., Mecocci P., Kivipelto M. Alzheimer's disease: clinical trials and drug development. Lancet Neurol 2010, 9:702-716.
36. Marcello E., Epis R., Saraceno C., Di Luca M. Synaptic dysfunction in Alzheimer's disease. Adv Exp Med Biol 2012, 970:573-601.
37. May P.C., Yang Z., Li W.Y., Hyslop P.A., Siemers E., Boggs L.N. Multi-compartmental pharmacodynamic assessment of the functional γ-secretase inhibitor LY450139 in PDAPP transgenic mice and non-transgenic mice. Neurobiol Aging 2004, 25(Suppl. 2). Abstract O3-06-07.
38. Mezler M., Barghorn S., Schoemaker H., Gross G., Nimmrich V. Aβ-amyloid oligomer directly modulates P/Q-type calcium currents in Xenopus oocytes. Br J Pharmacol 2012, 165:1572-1583.
39. Mitani Y., Yarimizu J., Saita K., Uchino H., Akashiba H., Shitaka Y., Ni K., Matsuoka N. Differential effects between g-secretase inhibitors and modulators on cognitive function in amyloid precursor protein-transgenic and nontransgenic mice. J Neurosci 2012, 32:2037-2050.
40. Mota S.I., Ferreira I.L., Rego A.C. Dysfunctional synapse in Alzheimer's disease - A focus on NMDA receptors. Neuropharmacology 2014, 76(Pt A):16-26.
41. Nagakura A., Shitaka Y., Yarimizu J., Matsuoka N. Characterization of cognitive deficits in a transgenic mouse model of Alzheimer's disease and effects of donepezil and memantine. Eur J Pharmacol 2013, 703:53-61.
42. Nisticò R., Pignatelli M., Piccinin S., Mercuri N.B., Collingridge G. Targeting synaptic dysfunction in Alzheimer's disease therapy. Mol Neurobiol 2012, 46:572-587.
43. Parameshwaran K., Dhanasekaran M., Suppiramaniam V. Amyloid beta peptides and glutamatergic synaptic dysregulation. Exp Neurol 2008, 210:7-13.
44. Paula-Lima A.C., Brito-Moreira J., Ferreira S.T. Deregulation of excitatory neurotransmission underlying synapse failure in Alzheimer's disease. J Neurochem 2013, 126:191-202.
45. Paxinos G., Franklin K. The mouse brain in stereotaxic coordinates 2012, Academic Press. 4th ed.
46. Penzes P., Vanleeuwen J.-E. Impaired regulation of synaptic actin cytoskeleton in Alzheimer's disease. Brain Res Rev 2011, 67:184-192.
47. Peretto I., Radaelli S., Parini C., Zandi M., Raveglia L.F., Dondio G., Fontanella L., Misiano P., Bigogno C., Rizzi A., Riccardi B., Biscaioli M., Marchetti S., Puccini P., Catinella S., Rondelli I., Cenacchi V., Bolzoni P.T., Caruso P., Villetti G., Facchinetti F., Del Giudice E., Moretto N., Imbimbo B.P. Synthesis and biological activity of flubiprofen analogues as selective inhibitors of beta-amyloid(1)(-)(42) secretion. J Med Chem 2005, 48:5705-5720.
48. Proctor D.-T., Coulson E.-J., Dodd P.-R. Post-synaptic scaffolding protein interactions with glutamate receptors in synaptic dysfunction and Alzheimer's disease. Prog Neurobiol 2011, 93:509-521.
49. Puoliväli J., Wang J., Heikkinen T., Heikkilä M., Tapiola T., van Groen T., Tanila H. Hippocampal Aβ 42 levels correlate with spatial memory deficit in APP and PS1 double transgenic mice. Neurobiol Dis 2002, 9:339-347.
50. Reisberg B., Doody R., Stöffler A., Schmitt F., Ferris S., Möbius H.J. Memantine in moderate-to-severe Alzheimer's disease. N Engl J Med 2003, 348:1333-1341. Memantine Study Group.
51. Revett T.-J., Baker G.-B., Jhamandas J., Kar S. Glutamate system, amyloid ß peptides and tau protein: functional interrelationships and relevance to Alzheimer disease pathology. J Psychiatry Neurosci 2013, 38:6-23.
52. Ross J., Sharma S., Winston J., Nunez M., Bottini G., Franceschi M., Scarpini E., Frigerio E., Fiorentini F., Fernandez M., Sivilia S., Giardino L., Calza L., Norris D., Cicirello H., Casula D., Imbimbo B.P. CHF5074 reduces biomarkers of neuroinflammation in patients with mild cognitive impairment: a 12-week, double-blind, placebo-controlled study. Curr Alzheimer Res 2013, 10:742-753.
53. Rotaru D.C., Barrionuevo G., Sesack S.R. Mediodorsal thalamic afferents to layer III of the rat prefrontal cortex: synaptic relationships to subclasses of interneurons. J Comp Neurol 2005, 490:220-238.
54. Schliebs R., Arendt T. The cholinergic system in aging and neuronal degeneration. Behav Brain Res 2011, 221:555-563.
55. Siemers E., Skinner M., Dean R.A., Gonzales C., Satterwhite J., Farlow M., Ness D., May P.C. Safety, tolerability, and changes in amyloid beta concentrations after administration of a gamma-secretase inhibitor in volunteers. Clin Neuropharmacol 2005, 28:126-132.
56. Sivilia S., Lorenzini L., Giuliani A., Gusciglio M., Fernandez M., Baldassarro V.A., Mangano C., Ferraro L., Pietrina V., Baroc M.-F., Viscomi R., Ottonello S., Villetta G., Imbimbo B.-P., Calzà L., Giardino L. Multi-target action of the novel anti-Alzheimer compound CHF5074: in vivo study of long term treatment in Tg2576 mice. BMC Neurosci 2013, 14:44.
57. Sokolow S., Luu S.-H., Nandy K., Miller C.-A., Vinters H.-V., Poon W.-W., Gylys K.-H. Preferential accumulation of amyloid-beta in presynaptic glutamatergic terminals (VGluT1 and VGluT2) in Alzheimer's disease cortex. Neurobiol Dis 2012, 45:381-387.
58. Talantova M., Sanz-Blasco S., Zhang X., Xia P., Akhtar M.-W., Okamoto S., Dziewczapolski G., Nakamura T., Cao G., Pratt A.-E., Kang Y.-J., Tu S., Molokanova E., McKercher S.-R., Hires S.-A., Sason H., Stouffer D.-G., Buczynski M.-W., Solomon J.-P., Michael S., Powers E.-T., Kelly J.-W., Roberts A., Tong G., Fang-Newmeyer T., Parker J., Holland E.-A., Zhang D., Nakanishi N., Chen H.-S., Wolosker H., Wang Y., Parsons L.-H., Ambasudhan R., Masliah E., Heinemann S.-F., Piña-Crespo J.-C., Lipton S.A. Aβ induces astrocytic glutamate release, extrasynaptic NMDA receptor activation, and synaptic loss. Proc Natl Acad Sci U S A 2013, 110:E2518-E2527.
59. Watanabe T., Yamagata N., Takasaki K., Sano K., Hayakawa K., Katsurabayashi S., Egashira N., Mishima K., Iwasaki K., Fujiwara M. Decreased acetylcholine release is correlated to memory impairment in the Tg2576 transgenic mouse model of Alzheimer's disease. Brain Res 2009, 1249:222-228.
60. Willis B.A., Zhang W., Ayan-Oshodi M., Lowe S.L., Annes W.F., Sirois P.J., Friedrich S., de la Peña A. Semagacestat pharmacokinetics are not significantly affected by formulation, food, or time of dosing in healthy participants. J Clin Pharmacol 2012, 52:904-913.
61. Xu Y., Yan J., Zhou P., Li J., Gao H., Xia Y., Wang Q. Neurotransmitter receptors and cognitive dysfunction in Alzheimer's disease and Parkinson's disease. Prog Neurobiol 2012, 7:1-13.
62. Yi P., Hadden C., Kulanthaivel P., Calvert N., Annes W., Brown T., Barbuch R.J., Chaudhary A., Ayan-Oshodi M.A., Ring B.J. Disposition and metabolism of semagacestat, a {gamma}-secretase inhibitor, in humans. Drug Metab Dispos 2010, 38:554-565.
63. Zhang W., Bai M., Xi Y., Hao J., Liu L., Mao N., Su C., Miao J., Li Z. Early memory deficits precede plaque deposition in APPswe/PS1dE9 mice: involvement of oxidative stress and cholinergic dysfunction. Free Radic Biol Med 2012, 52:1443-1452.