AAV.shRNA-mediated downregulation of ROCK2 attenuates degeneration of dopaminergic neurons in toxin-induced models of Parkinson's disease in vitro and in vivo

Neurobiology of Disease

Volumn 73, Issue , 2015, Pages 150-162

  Saal, Kim Ann ^a   Koch, Jan C ^a   Tatenhorst, Lars ^a   Szego, Éva M ^b   Ribas, Vinicius Toledo ^a   Michel, Uwe ^a   Bähr, Mathias ^a,c   Tönges, Lars ^a,c   Lingor, Paul ^a,c  

^a UNIVERSITY MEDICAL CENTER GÖTTINGEN   (Germany)

^b UNIVERSITY OF GÖTTINGEN   (Germany)

^c Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain   (Germany)

Author keywords

6 OHDA; AAV shRNA; Bcl 2; Dopaminergic degeneration; Dopaminergic midbrain neurons; Erk1; LIMK1; MPP+; Parkinson's disease; ROCK2

Indexed keywords

ADENOVIRUS VECTOR; LIM KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; PROTEIN BCL 2; RHO KINASE; SHORT HAIRPIN RNA; 3,4 DIHYDROXYPHENYLACETIC ACID; ADRENERGIC RECEPTOR STIMULATING AGENT; HOMOVANILLIC ACID; LIM KINASE; LIMK1 PROTEIN, RAT; OXIDOPAMINE; SMALL INTERFERING RNA; TYROSINE 3 MONOOXYGENASE;

ADENOVIRUS 7; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CELL COUNT; CELL SURVIVAL; CONTROLLED STUDY; DOPAMINERGIC NERVE CELL; DOWN REGULATION; DRUG EFFICACY; DRUG MECHANISM; DRUG RESPONSE; IMMUNOHISTOCHEMISTRY; IN VITRO STUDY; IN VIVO STUDY; MESENCEPHALON; MOUSE; NERVE FIBER GROWTH; NERVE REGENERATION; NEUROPROTECTION; NONHUMAN; NUCLEOTIDE SEQUENCE; PARKINSON DISEASE; PROTEIN EXPRESSION; PROTEIN TARGETING; VIRAL GENE DELIVERY SYSTEM; ANIMAL; COMPLICATION; DEPENDOPARVOVIRUS; DISEASE MODEL; GENE VECTOR; GENETICS; METABOLISM; NERVE DEGENERATION; PATHOLOGY; PHYSIOLOGY; PSYCHOMOTOR PERFORMANCE; RAT; SUBSTANTIA NIGRA; WISTAR RAT;

3,4-DIHYDROXYPHENYLACETIC ACID; ADRENERGIC AGENTS; ANIMALS; DEPENDOVIRUS; DISEASE MODELS, ANIMAL; DOPAMINERGIC NEURONS; DOWN-REGULATION; GENETIC VECTORS; HOMOVANILLIC ACID; LIM KINASES; NERVE DEGENERATION; OXIDOPAMINE; PARKINSON DISEASE; PSYCHOMOTOR PERFORMANCE; RATS; RATS, WISTAR; RHO-ASSOCIATED KINASES; RNA, SMALL INTERFERING; SUBSTANTIA NIGRA; TYROSINE 3-MONOOXYGENASE;

EID: 84908518157     PISSN: 09699961     EISSN: 1095953X     Source Type: Journal    
DOI: 10.1016/j.nbd.2014.09.013     Document Type: Article

References (50)

1. Alvarez-Fischer D., Henze C., Strenzke C., Westrich J., Ferger B., Höglinger G.U., Oertel W.H., Hartmann A. Characterization of the striatal 6-OHDA model of Parkinson's disease in wild type and alpha-synuclein-deleted mice. Exp. Neurol. 2008, 210:182-193. 10.1016/j.expneurol.2007.10.012.
2. Barcia C., Ros C.M., Annese V., Carrillo-de Sauvage M.A., Ros-Bernal F., Gómez A., Yuste J.E., Campuzano C.M., de Pablos V., Fernandez-Villalba E., Herrero M.T. ROCK/Cdc42-mediated microglial motility and gliapse formation lead to phagocytosis of degenerating dopaminergic neurons in vivo. Sci. Rep. 2012, 2:809. 10.1038/srep00809.
3. Bartlett J.S., Samulski R.J., McCown T.J. Selective and rapid uptake of adeno-associated virus type 2 in brain. Hum. Gene Ther. 1998, 9:1181-1186. 10.1089/hum.1998.9.8-1181.
4. Blits B., Derks S., Twisk J., Ehlert E., Prins J., Verhaagen J. Adeno-associated viral vector (AAV)-mediated gene transfer in the red nucleus of the adult rat brain: comparative analysis of the transduction properties of seven AAV serotypes and lentiviral vectors. J. Neurosci. Methods 2010, 185:257-263. 10.1016/j.jneumeth.2009.10.009.
5. Borrajo A., Rodriguez-Perez A.I., Villar-Cheda B., Guerra M.J., Labandeira-Garcia J.L. Inhibition of the microglial response is essential for the neuroprotective effects of Rho-kinase inhibitors on MPTP-induced dopaminergic cell death. Neuropharmacology 2014, 85:1-8. 10.1016/j.neuropharm.2014.05.021.
6. Burke R.E., O'Malley K. Axon degeneration in Parkinson's disease. Exp. Neurol. 2013, 246:72-83. 10.1016/j.expneurol.2012.01.011.
7. Davies S.P., Reddy H., Caivano M., Cohen P. Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem. J. 2000, 351:95-105.
8. Deng X., Kornblau S.M., Ruvolo P.P., May W.S. Regulation of Bcl2 phosphorylation and potential significance for leukemic cell chemoresistance. J. Natl. Cancer Inst. Monogr. 2001, 30-37.
9. Dimmeler S., Breitschopf K., Haendeler J., Zeiher A.M. Dephosphorylation targets Bcl-2 for ubiquitin-dependent degradation: a link between the apoptosome and the proteasome pathway. J. Exp. Med. 1999, 189:1815-1822.
10. Ding J., Li Q.-Y., Wang X., Sun C.-H., Lu C.-Z., Xiao B.-G. Fasudil protects hippocampal neurons against hypoxia-reoxygenation injury by suppressing microglial inflammatory responses in mice. J. Neurochem. 2010, 114:1619-1629.
11. Dučić T., Barski E., Salome M., Koch J.C., Bähr M., Lingor P. X-ray fluorescence analysis of iron and manganese distribution in primary dopaminergic neurons. J. Neurochem. 2013, 124:250-261. 10.1111/jnc.12073.
12. Duffy P., Schmandke A., Schmandke A., Sigworth J., Narumiya S., Cafferty W.B.J., Strittmatter S.M. Rho-associated kinase II (ROCKII) limits axonal growth after trauma within the adult mouse spinal cord. J. Neurosci. 2009, 29:15266-15276. 10.1523/JNEUROSCI.4650-09.2009.
13. Ebert S., Gerber J., Bader S., Mühlhauser F., Brechtel K., Mitchell T.J., Nau R. Dose-dependent activation of microglial cells by Toll-like receptor agonists alone and in combination. J. Neuroimmunol. 2005, 159(1-2):87-96. (Epub 2004 Dec 1.).
14. Endo M., Ohashi K., Sasaki Y., Goshima Y., Niwa R., Uemura T., Mizuno K. Control of growth cone motility and morphology by LIM kinase and Slingshot via phosphorylation and dephosphorylation of cofilin. J. Neurosci. 2003, 23:2527-2537.
15. Finkelstein D.I., Stanic D., Parish C.L., Tomas D., Dickson K., Horne M.K. Axonal sprouting following lesions of the rat substantia nigra. Neuroscience 2000, 97:99-112.
16. Geoffroy C.G., Zheng B. Myelin-associated inhibitors in axonal growth after CNS injury. Curr. Opin. Neurobiol. 2014, 27C:31-38. 10.1016/j.conb.2014.02.012.
17. Hashimoto R., Nakamura Y., Kosako H., Amano M., Kaibuchi K., Inagaki M., Takeda M. Distribution of Rho-kinase in the bovine brain. Biochem. Biophys. Res. Commun. 1999, 263:575-579. 10.1006/bbrc.1999.1409.
18. Hirata A., Inatani M., Inomata Y., Yonemura N., Kawaji T., Honjo M., Tanihara H. Y-27632, a Rho-associated protein kinase inhibitor, attenuates neuronal cell death after transient retinal ischemia. Graefes Arch. Clin. Exp. Ophthalmol. 2008, 246:51-59. 10.1007/s00417-007-0666-6.
19. Hsieh T.-H., Chen J.-J.J., Chen L.-H., Chiang P.-T., Lee H.-Y. Time-course gait analysis of hemiparkinsonian rats following 6-hydroxydopamine lesion. Behav. Brain Res. 2011, 222:1-9. 10.1016/j.bbr.2011.03.031.
20. Klein R.L., Meyer E.M., Peel A.L., Zolotukhin S., Meyers C., Muzyczka N., King M.A. Neuron-specific transduction in the rat septohippocampal or nigrostriatal pathway by recombinant adeno-associated virus vectors. Exp. Neurol. 1998, 150:183-194. 10.1006/exnr.1997.6736.
21. Koch J.C., Solis G.P., Bodrikov V., Michel U., Haralampieva D., Shypitsyna A., Tönges L., Bähr M., Lingor P., Stuermer C.A.O. Upregulation of reggie-1/flotillin-2 promotes axon regeneration in the rat optic nerve in vivo and neurite growth in vitro. Neurobiol. Dis. 2013, 51:168-176. 10.1016/j.nbd.2012.11.007.
22. Koch J.C., Tönges L., Barski E., Michel U., Bähr M., Lingor P. ROCK2 is a major regulator of axonal degeneration, neuronal death and axonal regeneration in the CNS. Cell Death Dis. 2014, 5:e1225. 10.1038/cddis.2014.191.
23. Lau C.L., Perreau V.M., Chen M.J., Cate H.S., Merlo D., Cheung N.S., O'Shea R.D., Beart P.M. Transcriptomic profiling of astrocytes treated with the Rho kinase inhibitor fasudil reveals cytoskeletal and pro-survival responses. J. Cell. Physiol. 2012, 227:1199-1211. 10.1002/jcp.22838.
24. Lingor P., Unsicker K., Krieglstein K. Midbrain dopaminergic neurons are protected from radical induced damage by GDF-5 application. Short communication. J. Neural Transm. 1999, 106:139-144.
25. Lingor P., Teusch N., Schwarz K., Mueller R., Mack H., Bähr M., Mueller B.K. Inhibition of Rho kinase (ROCK) increases neurite outgrowth on chondroitin sulphate proteoglycan in vitro and axonal regeneration in the adult optic nerve in vivo. J. Neurochem. 2007, 103:181-189. 10.1111/j.1471-4159.2007.04756.x.
26. Lingor P., Tönges L., Pieper N., Bermel C., Barski E., Planchamp V., Bähr M. ROCK inhibition and CNTF interact on intrinsic signalling pathways and differentially regulate survival and regeneration in retinal ganglion cells. Brain 2008, 131:250-263. 10.1093/brain/awm284.
27. Löw K., Aebischer P. Use of viral vectors to create animal models for Parkinson's disease. Neurobiol. Dis. 2012, 48:189-201. 10.1016/j.nbd.2011.12.038.
28. McCown T.J., Xiao X., Li J., Breese G.R., Samulski R.J. Differential and persistent expression patterns of CNS gene transfer by an adeno-associated virus (AAV) vector. Brain Res. 1996, 713:99-107.
29. Meijering E., Jacob M., Sarria J.-C.F., Steiner P., Hirling H., Unser M. Design and validation of a tool for neurite tracing and analysis in fluorescence microscopy images. Cytometry A 2004, 58:167-176. 10.1002/cyto.a.20022.
30. Michel U., Malik I., Ebert S., Bähr M., Kügler S. Long-term in vivo and in vitro AAV-2-mediated RNA interference in rat retinal ganglion cells and cultured primary neurons. Biochem. Biophys. Res. Commun. 2005, 326:307-312. 10.1016/j.bbrc.2004.11.029.
31. Rodriguez-Perez A.I., Dominguez-Meijide A., Lanciego J.L., Guerra M.J., Labandeira-Garcia J.L. Inhibition of Rho kinase mediates the neuroprotective effects of estrogen in the MPTP model of Parkinson's disease. Neurobiol. Dis. 2013, 58:209-219. 10.1016/j.nbd.2013.06.004.
32. Schallert T., Fleming S.M., Leasure J.L., Tillerson J.L., Bland S.T. CNS plasticity and assessment of forelimb sensorimotor outcome in unilateral rat models of stroke, cortical ablation, parkinsonism and spinal cord injury. Neuropharmacology 2000, 39:777-787.
33. Stott S.R.W., Barker R.A. Time course of dopamine neuron loss and glial response in the 6-OHDA striatal mouse model of Parkinson's disease. Eur. J. Neurosci. 2014, 39:1042-1056. 10.1111/ejn.12459.
34. Sun X., Minohara M., Kikuchi H., Ishizu T., Tanaka M., Piao H., Osoegawa M., Ohyagi Y., Shimokawa H., Kira J.-I. The selective Rho-kinase inhibitor Fasudil is protective and therapeutic in experimental autoimmune encephalomyelitis. J. Neuroimmunol. 2006, 180:126-134. 10.1016/j.jneuroim.2006.06.027.
35. Tatenhorst L., Tönges L., Saal K.-A., Koch J.C., Szego E.M., Bähr M., Lingor P. Rho kinase inhibition by fasudil in the striatal 6-hydroxydopamine lesion mouse model of Parkinson disease. J. Neuropathol. Exp. Neurol. 2014, 73:770-779. 10.1097/NEN.0000000000000095.
36. Tenenbaum L., Jurysta F., Stathopoulos A., Puschban Z., Melas C., Hermens W.T., verhaagen J., Pichon B., Velu T., Levivier M. Tropism of AAV-2 vectors for neurons of the globus pallidus. Neuroreport. 2000, 10(11):2277-2283.
37. Tenenbaum L., Chtarto A., Lehtonen E., Velu T., Brotchi J., Levivier M. Recombinant AAV-mediated gene delivery to the central nervous system. J. Gene Med. 2004, 6(Suppl. 1):S212-S222. 10.1002/jgm.506.
38. Tönges L., Koch J.-C., Bähr M., Lingor P. ROCKing regeneration: rho kinase inhibition as molecular target for neurorestoration. Front. Mol. Neurosci. 2011, 4(39). 10.3389/fnmol.2011.00039.
39. Tönges L., Planchamp V., Koch J.-C., Herdegen T., Bähr M., Lingor P. JNK isoforms differentially regulate neurite growth and regeneration in dopaminergic neurons in vitro. J. Mol. Neurosci. 2011, 45:284-293. 10.1007/s12031-011-9519-1.
40. Tönges L., Frank T., Tatenhorst L., Saal K.A., Koch J.C., Szego É.M., Bähr M., Weishaupt J.H., Lingor P. Inhibition of rho kinase enhances survival of dopaminergic neurons and attenuates axonal loss in a mouse model of Parkinson's disease. Brain 2012, 135:3355-3370. 10.1093/brain/aws254.
41. Tönges L., Günther R., Suhr M., Jansen J., Balck A., Saal K.-A., Barski E., Nientied T., Götz A.A., Koch J.-C., Mueller B.K., Weishaupt J.H., Sereda M.W., Hanisch U.-K., Bähr M., Lingor P. Rho kinase inhibition modulates microglia activation and improves survival in a model of amyotrophic lateral sclerosis. Glia 2014, 62:217-232. 10.1002/glia.22601.
42. Tura A., Schuettauf F., Monnier P.P., Bartz-Schmidt K.U., Henke-Fahle S. Efficacy of Rho-kinase inhibition in promoting cell survival and reducing reactive gliosis in the rodent retina. Invest. Ophthalmol. Vis. Sci. 2009, 50:452-461. 10.1167/iovs.08-1973.
43. Ungerstedt U. Postsynaptic supersensitivity after 6-hydroxy-dopamine induced degeneration of the nigro-striatal dopamine system. Acta Physiol. Scand. Suppl. 1971, 367:69-93.
44. Vandeputte C., Taymans J.-M., Casteels C., Coun F., Ni Y., Van Laere K., Baekelandt V. Automated quantitative gait analysis in animal models of movement disorders. BMC Neurosci. 2010, 11:92. 10.1186/1471-2202-11-92.
45. Villar-Cheda B., Dominguez-Meijide A., Joglar B., Rodriguez-Perez A.I., Guerra M.J., Labandeira-Garcia J.L. Involvement of microglial RhoA/Rho-kinase pathway activation in the dopaminergic neuron death. Role of angiotensin via angiotensin type 1 receptors. Neurobiol. Dis. 2012, 47:268-279. 10.1016/j.nbd.2012.04.010.
46. Yamashita K., Kotani Y., Nakajima Y., Shimazawa M., Yoshimura S., Nakashima S., Iwama T., Hara H. Fasudil, a Rho kinase (ROCK) inhibitor, protects against ischemic neuronal damage in vitro and in vivo by acting directly on neurons. Brain Res. 2007, 1154:215-224. 10.1016/j.brainres.2007.04.013.
47. Yang N., Higuchi O., Ohashi K., Nagata K., Wada A., Kangawa K., Nishida E., Mizuno K. Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin reorganization. Nature 1998, 393:809-812. 10.1038/31735.
48. Zar J.H. Biostatistical Analysis 1999, Prentice Hall, Upper Saddle River, NJ. 4th edition.
49. Zhang J., Niu N., Wang M., McNutt M.A., Zhang D., Zhang B., Lu S., Liu Y., Liu Z. Neuron-derived IgG protects dopaminergic neurons from insult by 6-OHDA and activates microglia through the FcγR I and TLR4 pathways. Int. J. Biochem. Cell Biol. 2013, 45:1911-1920. 10.1016/j.biocel.2013.06.005.
50. Zolotukhin S., Byrne B.J., Mason E., Zolotukhin I., Potter M., Chesnut K., Summerford C., Samulski R.J., Muzyczka N. Recombinant adeno-associated virus purification using novel methods improves infectious titer and yield. Gene Ther. 1999, 6:973-985. 10.1038/sj.gt.3300938.