The mGluR5 positive allosteric modulator, CDPPB, ameliorates pathology and phenotypic signs of a mouse model of Huntington's disease

Neurobiology of Disease

Volumn 73, Issue , 2015, Pages 163-173

  Doria, J G ^a   de Souza, J M ^a   Andrade, J N ^a   Rodrigues, H A ^a   Guimaraes, I M ^a   Carvalho, T G ^a   Guatimosim, C ^a   Dobransky, T ^b   Ribeiro, F M ^a  

^a FEDERAL UNIVERSITY OF MINAS GERAIS   (Brazil)

^b DB Biotech   (Slovakia)

Author keywords

BDNF; CDPPB; Huntington's disease; Memory and cognition; Metabotropic glutamate receptors; Neuroprotection

Indexed keywords

3 CYANO N (1,3 DIPHENYL 1H PYRAZOL 5 YL)BENZAMIDE; BRAIN DERIVED NEUROTROPHIC FACTOR; HUNTINGTIN; MESSENGER RNA; METABOTROPIC RECEPTOR 5; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; NEUROPROTECTIVE AGENT; PROTEIN KINASE B; UNCLASSIFIED DRUG; 3-CYANO-N-(1,3-DIPHENYL-1H-PYRAZOL-5-YL)BENZAMIDE; BENZAMIDE DERIVATIVE; GLUTAMIC ACID; HTT PROTEIN, HUMAN; MITOGEN ACTIVATED PROTEIN KINASE; NERVE PROTEIN; PYRAZOLE DERIVATIVE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL SURVIVAL; CONTROLLED STUDY; DRUG EFFICACY; EMBRYO; ENZYME PHOSPHORYLATION; GENE EXPRESSION; HISTOPATHOLOGY; HUNTINGTON CHOREA; IN VITRO STUDY; IN VIVO STUDY; LONG TERM CARE; MEMORY DISORDER; MOTOR DYSFUNCTION; MOUSE; MOUSE MODEL; NERVE CELL NECROSIS; NEUROPATHOLOGY; NONHUMAN; PHENOTYPE; PROTEIN AGGREGATION; PROTEIN EXPRESSION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; STEREOTYPY; SYMPTOM; TREATMENT DURATION; AGE; ANIMAL; ANIMAL EMBRYO; CELL CULTURE; CELL DEATH; CORPUS STRIATUM; CYTOLOGY; DISEASE MODEL; DRUG EFFECTS; GENETICS; HUMAN; HUNTINGTON DISEASE; METABOLISM; MITOCHONDRION; MOTOR ACTIVITY; NERVE CELL; PATHOLOGY; PATHOPHYSIOLOGY; RECOGNITION; SYNAPSE; TRANSGENIC MOUSE; ULTRASTRUCTURE;

AGE FACTORS; ANIMALS; BENZAMIDES; CELL DEATH; CELLS, CULTURED; CORPUS STRIATUM; DISEASE MODELS, ANIMAL; EMBRYO, MAMMALIAN; EXTRACELLULAR SIGNAL-REGULATED MAP KINASES; GLUTAMIC ACID; HUMANS; HUNTINGTON DISEASE; MICE; MICE, TRANSGENIC; MITOCHONDRIA; MOTOR ACTIVITY; NERVE TISSUE PROTEINS; NEURONS; PYRAZOLES; RECOGNITION (PSYCHOLOGY); SIGNAL TRANSDUCTION; SYNAPSES;

EID: 84908319342     PISSN: 09699961     EISSN: 1095953X     Source Type: Journal    
DOI: 10.1016/j.nbd.2014.08.021     Document Type: Article

References (45)

1. Agerman K., Hjerling-Leffler J., Blanchard M.P., Scarfone E., Canlon B., Nosrat C., Ernfors P. BDNF gene replacement reveals multiple mechanisms for establishing neurotrophin specificity during sensory nervous system development. Development 2003, 130:1479-1491.
2. Altar C.A., Cai N., Bliven T., Juhasz M., Conner J.M., Acheson A.L., Lindsay R.M., Wiegand S.J. Anterograde transport of brain-derived neurotrophic factor and its role in the brain. Nature 1997, 389:856-860.
3. Anborgh P.H., Godin C., Pampillo M., Dhami G.K., Dale L.B., Cregan S.P., Truant R., Ferguson S.S. Inhibition of metabotropic glutamate receptor signaling by the huntingtin-binding protein optineurin. J. Biol. Chem. 2005, 280:34840-34848.
4. Ayala J.E., Chen Y., Banko J.L., Sheffler D.J., Williams R., Telk A.N., Watson N.L., Xiang Z., Zhang Y., et al. mGluR5 positive allosteric modulators facilitate both hippocampal LTP and LTD and enhance spatial learning. Neuropsychopharmacology 2009, 34:2057-2071.
5. Balazs R. Trophic effect of glutamate. Curr. Top. Med. Chem. 2006, 6:961-968.
6. Becherer U., Guatimosim C., Betz W. Effects of staurosporine on exocytosis and endocytosis at frog motor nerve terminals. J. Neurosci. 2001, 21:782-787.
7. Calabresi P., Centonze D., Pisani A., Bernardi G. Metabotropic glutamate receptors and cell-type-specific vulnerability in the striatum: implication for ischemia and Huntington's disease. Exp. Neurol. 1999, 158:97-108.
8. Canals J.M., Pineda J.R., Torres-Peraza J.F., Bosch M., Martin-Ibanez R., Munoz M.T., Mengod G., Ernfors P., Alberch J. Brain-derived neurotrophic factor regulates the onset and severity of motor dysfunction associated with enkephalinergic neuronal degeneration in Huntington's disease. J. Neurosci. 2004, 24:7727-7739.
9. Chen T., Cao L., Dong W., Luo P., Liu W., Qu Y., Fei Z. Protective effects of mGluR5 positive modulators against traumatic neuronal injury through PKC-dependent activation of MEK/ERK pathway. Neurochem. Res. 2012, 37:983-990.
10. Cummings D.M., Milnerwood A.J., Dallerac G.M., Waights V., Brown J.Y., Vatsavayai S.C., Hirst M.C., Murphy K.P. Aberrant cortical synaptic plasticity and dopaminergic dysfunction in a mouse model of Huntington's disease. Hum. Mol. Genet. 2006, 15:2856-2868.
11. Datta S.R., Brunet A., Greenberg M.E. Cellular survival: a play in three Akts. Genes Dev. 1999, 13:2905-2927.
12. DiFiglia M. Excitotoxic injury of the neostriatum: a model for Huntington's disease. Trends Neurosci. 1990, 13:286-289.
13. Doria J.G., Silva F.R., de Souza J.M., Vieira L.B., Carvalho T.G., Reis H.J., Pereira G.S., Dobransky T., Ribeiro F.M. Metabotropic glutamate receptor 5 positive allosteric modulators are neuroprotective in a mouse model of Huntington's disease. Br. J. Pharmacol. 2013, 169:909-921.
14. Figurov A., Pozzo-Miller L.D., Olafsson P., Wang T., Lu B. Regulation of synaptic responses to high-frequency stimulation and LTP by neurotrophins in the hippocampus. Nature 1996, 381:706-709.
15. Gauthier L.R., Charrin B.C., Borrell-Pages M., Dompierre J.P., Rangone H., Cordelieres F.P., De Mey J., MacDonald M.E., Lessmann V., et al. Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules. Cell 2004, 118:127-138.
16. Gray M., Shirasaki D.I., Cepeda C., Andre V.M., Wilburn B., Lu X.H., Tao J., Yamazaki I., Li S.H., et al. Full-length human mutant huntingtin with a stable polyglutamine repeat can elicit progressive and selective neuropathogenesis in BACHD mice. J. Neurosci. 2008, 28:6182-6195.
17. Gray L.J., Hannan A.J., Zhang X. Metabotropic glutamate receptors as targets for novel antipsychotic treatments. Curr. Pharm. Biotechnol. 2012, 13:1522-1534.
18. Group T.H.s.D.C.R. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 1993, 72:971-983.
19. Han Y., Kaeser P.S., Sudhof T.C., Schneggenburger R. RIM determines Ca(2)+ channel density and vesicle docking at the presynaptic active zone. Neuron 2011, 69:304-316.
20. Humbert S., Bryson E.A., Cordelieres F.P., Connors N.C., Datta S.R., Finkbeiner S., Greenberg M.E., Saudou F. The IGF-1/Akt pathway is neuroprotective in Huntington's disease and involves Huntingtin phosphorylation by Akt. Dev. Cell 2002, 2:831-837.
21. Kandel E.S., Hay N. The regulation and activities of the multifunctional serine/threonine kinase Akt/PKB. Exp. Cell Res. 1999, 253:210-229.
22. Kang H., Schuman E.M. Long-lasting neurotrophin-induced enhancement of synaptic transmission in the adult hippocampus. Science 1995, 267:1658-1662.
23. Li S.H., Li X.J. Huntingtin-protein interactions and the pathogenesis of Huntington's disease. Trends Genet. 2004, 20:146-154.
24. Li X.J., Li S. Influence of species differences on the neuropathology of transgenic Huntington's disease animal models. J. Genet. Genom. 2012, 39:239-245.
25. Menalled L., El-Khodor B.F., Patry M., Suarez-Farinas M., Orenstein S.J., Zahasky B., Leahy C., Wheeler V., Yang X.W., et al. Systematic behavioral evaluation of Huntington's disease transgenic and knock-in mouse models. Neurobiol. Dis. 2009, 35:319-336.
26. Milnerwood A.J., Raymond L.A. Corticostriatal synaptic function in mouse models of Huntington's disease: early effects of huntingtin repeat length and protein load. J. Physiol. 2007, 585:817-831.
27. Reichel C.M., Schwendt M., McGinty J.F., Olive M.F., See R.E. Loss of object recognition memory produced by extended access to methamphetamine self-administration is reversed by positive allosteric modulation of metabotropic glutamate receptor 5. Neuropsychopharmacology 2011, 36:782-792.
28. Reitz C., Mayeux R. Alzheimer disease: epidemiology, diagnostic criteria, risk factors and biomarkers. Biochem. Pharmacol. 2014, 88:640-651.
29. Ribeiro F.M., Paquet M., Ferreira L.T., Cregan T., Swan P., Cregan S.P., Ferguson S.S. Metabotropic glutamate receptor-mediated cell signaling pathways are altered in a mouse model of Huntington's disease. J. Neurosci. 2010, 30:316-324.
30. Ribeiro F.M., Camargos E.R., de Souza L.C., Teixeira A.L. Animal models of neurodegenerative diseases. Rev. Bras. Psiquiatr. 2013, 35(Suppl. 2):S82-S91.
31. Ribeiro F.M., Devries R.A., Hamilton A., Guimaraes I.M., Cregan S.P., Pires R.G., Ferguson S.S. Metabotropic glutamate receptor 5 knockout promotes motor and biochemical alterations in a mouse model of Huntington's disease. Hum. Mol. Genet. 2014, 23:2030-2042.
32. Rodrigues H.A., Fonseca Mde C., Camargo W.L., Lima P.M., Martinelli P.M., Naves L.A., Prado V.F., Prado M.A., Guatimosim C. Reduced expression of the vesicular acetylcholine transporter and neurotransmitter content affects synaptic vesicle distribution and shape in mouse neuromuscular junction. PLoS One 2013, 8:e78342.
33. Rodriguez A.L., Grier M.D., Jones C.K., Herman E.J., Kane A.S., Smith R.L., Williams R., Zhou Y., Marlo J.E., et al. Discovery of novel allosteric modulators of metabotropic glutamate receptor subtype 5 reveals chemical and functional diversity and in vivo activity in rat behavioral models of anxiolytic and antipsychotic activity. Mol. Pharmacol. 2010, 78:1105-1123.
34. Simonyi A., Schachtman T.R., Christoffersen G.R. Metabotropic glutamate receptor subtype 5 antagonism in learning and memory. Eur. J. Pharmacol. 2010, 639:17-25.
35. Spear N., Gadient R.A., Wilkins D.E., Do M., Smith J.S., Zeller K.L., Schroeder P., Zhang M., Arora J., et al. Preclinical profile of a novel metabotropic glutamate receptor 5 positive allosteric modulator. Eur. J. Pharmacol. 2011, 659:146-154.
36. Tanaka J., Horiike Y., Matsuzaki M., Miyazaki T., Ellis-Davies G.C., Kasai H. Protein synthesis and neurotrophin-dependent structural plasticity of single dendritic spines. Science 2008, 319:1683-1687.
37. Tang T.S., Tu H., Chan E.Y., Maximov A., Wang Z., Wellington C.L., Hayden M.R., Bezprozvanny I. Huntingtin and huntingtin-associated protein 1 influence neuronal calcium signaling mediated by inositol-(1,4,5) triphosphate receptor type 1. Neuron 2003, 39:227-239.
38. 2+ signaling and apoptosis of medium spiny neurons in Huntington's disease. Proc. Natl. Acad. Sci. U. S. A. 2005, 102:2602-2607.
39. Trushina E., Dyer R.B., Badger J.D., Ure D., Eide L., Tran D.D., Vrieze B.T., Legendre-Guillemin V., McPherson P.S., et al. Mutant huntingtin impairs axonal trafficking in mammalian neurons in vivo and in vitro. Mol. Cell. Biol. 2004, 24:8195-8209.
40. Uslaner J.M., Parmentier-Batteur S., Flick R.B., Surles N.O., Lam J.S., McNaughton C.H., Jacobson M.A., Hutson P.H. Dose-dependent effect of CDPPB, the mGluR5 positive allosteric modulator, on recognition memory is associated with GluR1 and CREB phosphorylation in the prefrontal cortex and hippocampus. Neuropharmacology 2009, 57:531-538.
41. Vonsattel J.P., DiFiglia M. Huntington disease. J. Neuropathol. Exp. Neurol. 1998, 57:369-384.
42. Vonsattel J.P., Myers R.H., Stevens T.J., Ferrante R.J., Bird E.D., Richardson E.P. Neuropathological classification of Huntington's disease. J. Neuropathol. Exp. Neurol. 1985, 44:559-577.
43. Warby S.C., Doty C.N., Graham R.K., Shively J., Singaraja R.R., Hayden M.R. Phosphorylation of huntingtin reduces the accumulation of its nuclear fragments. Mol. Cell. Neurosci. 2009, 40:121-127.
44. Young A.B. Huntingtin in health and disease. J. Clin. Invest. 2003, 111:299-302.
45. Zuccato C., Ciammola A., Rigamonti D., Leavitt B.R., Goffredo D., Conti L., MacDonald M.E., Friedlander R.M., Silani V., et al. Loss of huntingtin-mediated BDNF gene transcription in Huntington's disease. Science 2001, 293:493-498.