Chronic Pharmacological mGluR5 Inhibition Prevents Cognitive Impairment and Reduces Pathogenesis in an Alzheimer Disease Mouse Model

Cell Reports

Volumn 15, Issue 9, 2016, Pages 1859-1865

  Hamilton, Alison ^a   Vasefi, Maryam ^b   Vander Tuin, Cheryl ^b   McQuaid, Robyn J ^c   Anisman, Hymie ^c   Ferguson, Stephen S G ^a  

^a UNIVERSITY OF OTTAWA   (Canada)

^b ROBARTS RESEARCH INSTITUTE   (Canada)

^c CARLETON UNIVERSITY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

2 CHLORO 4 [[2,5 DIMETHYL 1 [4 (TRIFLUOROMETHOXY)PHENYL] 1H IMIDAZOL 4 YL]ETHYNYL]PYRIDINE; BASIMGLURANT; METABOTROPIC RECEPTOR 5; METABOTROPIC RECEPTOR ANTAGONIST; UNCLASSIFIED DRUG; 2-CHLORO-4-((2,5-DIMETHYL-1-(4-(TRIFLUOROMETHOXY)PHENYL)-1H-IMIDAZOL-4-YL)ETHYNYL)PYRIDINE; AMYLOID BETA PROTEIN; IMIDAZOLE DERIVATIVE; PYRIDINE DERIVATIVE;

ALZHEIMER DISEASE; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; COGNITIVE DEFECT; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG POTENCY; DRUG SELECTIVITY; DRUG STRUCTURE; ENZYME INHIBITION; FRAGILE X SYNDROME; IN VIVO STUDY; MAJOR DEPRESSION; MALE; MOUSE; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; AMYLOID PLAQUE; ANIMAL; ANTAGONISTS AND INHIBITORS; C57BL MOUSE; COMPLICATION; DISEASE MODEL; DRUG EFFECTS; MEMORY; METABOLISM; PATHOLOGY; PATHOPHYSIOLOGY; TRANSGENIC MOUSE;

ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; ANIMALS; COGNITIVE DYSFUNCTION; DISEASE MODELS, ANIMAL; IMIDAZOLES; MEMORY; MICE, INBRED C57BL; MICE, TRANSGENIC; PLAQUE, AMYLOID; PYRIDINES; RECEPTOR, METABOTROPIC GLUTAMATE 5;

EID: 84971304022     PISSN: None     EISSN: 22111247     Source Type: Journal    
DOI: 10.1016/j.celrep.2016.04.077     Document Type: Article

References (20)

1. Citron M., Diehl T.S., Gordon G., Biere A.L., Seubert P., Selkoe D.J. Evidence that the 42- and 40-amino acid forms of amyloid beta protein are generated from the beta-amyloid precursor protein by different protease activities. Proc. Natl. Acad. Sci. USA 1996, 93:13170-13175.
2. Haas L.T., Kostylev M.A., Strittmatter S.M. Therapeutic molecules and endogenous ligands regulate the interaction between brain cellular prion protein (PrPC) and metabotropic glutamate receptor 5 (mGluR5). J. Biol. Chem. 2014, 289:28460-28477.
3. Hamilton A., Esseltine J.L., DeVries R.A., Cregan S.P., Ferguson S.S.G. Metabotropic glutamate receptor 5 knockout reduces cognitive impairment and pathogenesis in a mouse model of Alzheimer's disease. Mol. Brain 2014, 7:40.
4. Hu N.W., Nicoll A.J., Zhang D., Mably A.J., O'Malley T., Purro S.A., Terry C., Collinge J., Walsh D.M., Rowan M.J. mGlu5 receptors and cellular prion protein mediate amyloid-β-facilitated synaptic long-term depression in vivo. Nat. Commun. 2014, 5:3374.
5. Kamenetz F., Tomita T., Hsieh H., Seabrook G., Borchelt D., Iwatsubo T., Sisodia S., Malinow R. APP processing and synaptic function. Neuron 2003, 37:925-937.
6. Lalonde R., Kim H.D., Maxwell J.A., Fukuchi K. Exploratory activity and spatial learning in 12-month-old APP(695)SWE/co+PS1/DeltaE9 mice with amyloid plaques. Neurosci. Lett. 2005, 390:87-92.
7. 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.
8. Li S., Hong S., Shepardson N.E., Walsh D.M., Shankar G.M., Selkoe D. Soluble oligomers of amyloid Beta protein facilitate hippocampal long-term depression by disrupting neuronal glutamate uptake. Neuron 2009, 62:788-801.
9. Lindemann L., Jaeschke G., Michalon A., Vieira E., Honer M., Spooren W., Porter R., Hartung T., Kolczewski S., Büttelmann B., et al. CTEP: a novel, potent, long-acting, and orally bioavailable metabotropic glutamate receptor 5 inhibitor. J. Pharmacol. Exp. Ther. 2011, 339:474-486.
10. Lindemann L., Porter R.H., Scharf S.H., Kuennecke B., Bruns A., von Kienlin M., Harrison A.C., Paehler A., Funk C., Gloge A., et al. Pharmacology of basimglurant (RO4917523, RG7090), a unique metabotropic glutamate receptor 5 negative allosteric modulator in clinical development for depression. J. Pharmacol. Exp. Ther. 2015, 353:213-233.
11. Lu Y.M., Jia Z., Janus C., Henderson J.T., Gerlai R., Wojtowicz J.M., Roder J.C. Mice lacking metabotropic glutamate receptor 5 show impaired learning and reduced CA1 long-term potentiation (LTP) but normal CA3 LTP. J. Neurosci. 1997, 17:5196-5205.
12. McGowan E., Pickford F., Kim J., Onstead L., Eriksen J., Yu C., Skipper L., Murphy M.P., Beard J., Das P., et al. Abeta42 is essential for parenchymal and vascular amyloid deposition in mice. Neuron 2005, 47:191-199.
13. Michalon A., Sidorov M., Ballard T.M., Ozmen L., Spooren W., Wettstein J.G., Jaeschke G., Bear M.F., Lindemann L. Chronic pharmacological mGlu5 inhibition corrects fragile X in adult mice. Neuron 2012, 74:49-56.
14. Rammes G., Hasenjäger A., Sroka-Saidi K., Deussing J.M., Parsons C.G. Therapeutic significance of NR2B-containing NMDA receptors and mGluR5 metabotropic glutamate receptors in mediating the synaptotoxic effects of β-amyloid oligomers on long-term potentiation (LTP) in murine hippocampal slices. Neuropharmacology 2011, 60:982-990.
15. Renner M., Lacor P.N., Velasco P.T., Xu J., Contractor A., Klein W.L., Triller A. Deleterious effects of amyloid beta oligomers acting as an extracellular scaffold for mGluR5. Neuron 2010, 66:739-754.
16. Ribeiro F.M., Paquet M., Cregan S.P., Ferguson S.S.G. Group I metabotropic glutamate receptor signalling and its implication in neurological disease. CNS Neurol. Disord. Drug Targets 2010, 9:574-595.
17. Shankar G.M., Li S., Mehta T.H., Garcia-Munoz A., Shepardson N.E., Smith I., Brett F.M., Farrell M.A., Rowan M.J., Lemere C.A., et al. Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat. Med. 2008, 14:837-842.
18. Sokol D.K., Maloney B., Long J.M., Ray B., Lahiri D.K. Autism, Alzheimer disease, and fragile X: APP, FMRP, and mGluR5 are molecular links. Neurology 2011, 76:1344-1352.
19. Um J.W., Kaufman A.C., Kostylev M., Heiss J.K., Stagi M., Takahashi H., Kerrisk M.E., Vortmeyer A., Wisniewski T., Koleske A.J., et al. Metabotropic glutamate receptor 5 is a coreceptor for Alzheimer aβ oligomer bound to cellular prion protein. Neuron 2013, 79:887-902.
20. Wang Q., Walsh D.M., Rowan M.J., Selkoe D.J., Anwyl R. Block of long-term potentiation by naturally secreted and synthetic amyloid beta-peptide in hippocampal slices is mediated via activation of the kinases c-Jun N-terminal kinase, cyclin-dependent kinase 5, and p38 mitogen-activated protein kinase as well as metabotropic glutamate receptor type 5. J. Neurosci. 2004, 24:3370-3378.