rAAV-based brain slice culture models of Alzheimer's and Parkinson's disease inclusion pathologies.
Alzheimer Disease
/ pathology
Animals
Brain
/ metabolism
Dependovirus
/ genetics
Drug Evaluation, Preclinical
/ methods
Gene Expression
Humans
Mice, Inbred C3H
Mice, Transgenic
Microorganisms, Genetically-Modified
Mutation
Neurons
/ pathology
Organ Culture Techniques
Parkinson Disease
/ pathology
Transduction, Genetic
Transgenes
alpha-Synuclein
/ genetics
tau Proteins
/ genetics
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
04 03 2019
04 03 2019
Historique:
received:
26
11
2018
revised:
09
01
2019
accepted:
10
01
2019
pubmed:
17
2
2019
medline:
24
3
2020
entrez:
17
2
2019
Statut:
ppublish
Résumé
It has been challenging to produce ex vivo models of the inclusion pathologies that are hallmark pathologies of many neurodegenerative diseases. Using three-dimensional mouse brain slice cultures (BSCs), we have developed a paradigm that rapidly and robustly recapitulates mature neurofibrillary inclusion and Lewy body formation found in Alzheimer's and Parkinson's disease, respectively. This was achieved by transducing the BSCs with recombinant adeno-associated viruses (rAAVs) that express α-synuclein or variants of tau. Notably, the tauopathy BSC model enables screening of small molecule therapeutics and tracking of neurodegeneration. More generally, the rAAV BSC "toolkit" enables efficient transduction and transgene expression from neurons, microglia, astrocytes, and oligodendrocytes, alone or in combination, with transgene expression lasting for many months. These rAAV-based BSC models provide a cost-effective and facile alternative to in vivo studies, and in the future can become a widely adopted methodology to explore physiological and pathological mechanisms related to brain function and dysfunction.
Identifiants
pubmed: 30770411
pii: jem.20182184
doi: 10.1084/jem.20182184
pmc: PMC6400529
doi:
Substances chimiques
MAPT protein, human
0
alpha-Synuclein
0
tau Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
539-555Subventions
Organisme : NIA NIH HHS
ID : P50 AG047266
Pays : United States
Organisme : NIH HHS
ID : S10 OD020026
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG055798
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG046139
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG018454
Pays : United States
Informations de copyright
© 2019 Croft et al.
Références
Am J Pathol. 2008 Mar;172(3):786-98
pubmed: 18258852
Lancet Neurol. 2011 Sep;10(9):785-96
pubmed: 21802369
Curr Alzheimer Res. 2016;13(4):370-80
pubmed: 26567746
Neurosci Lett. 1992 Nov 23;147(1):58-62
pubmed: 1336152
Mol Neurodegener. 2013 May 28;8:17
pubmed: 23714769
Biochem Soc Trans. 2010 Aug;38(4):1016-20
pubmed: 20658996
N Engl J Med. 2013 Jan 10;368(2):117-27
pubmed: 23150934
J Neuropathol Exp Neurol. 1999 Jun;58(6):667-77
pubmed: 10374757
Acta Neuropathol. 2002 Jan;103(1):26-35
pubmed: 11837744
Nat Cell Biol. 2002 Feb;4(2):160-4
pubmed: 11813001
Alzheimers Dement. 2016 Oct;12(10):1051-1065
pubmed: 27751442
JAMA Neurol. 2017 Dec 1;74(12):1464-1472
pubmed: 29059326
Nat Med. 2004 Oct;10(10):1055-63
pubmed: 15459709
Acta Neuropathol Commun. 2017 Jul 31;5(1):58
pubmed: 28760159
Acta Neuropathol. 2017 May;133(5):665-704
pubmed: 28386764
EMBO Rep. 2016 Apr;17(4):530-51
pubmed: 26931567
Ann Neurol. 1997 Jan;41(1):17-24
pubmed: 9005861
EMBO Rep. 2016 Apr;17(4):552-69
pubmed: 26931569
Hum Mutat. 2004 Oct;24(4):277-95
pubmed: 15365985
EMBO J. 1995 Apr 3;14(7):1304-13
pubmed: 7729409
Alzheimers Res Ther. 2014 Jan 02;6(1):1
pubmed: 24382028
J Neurocytol. 2003 Nov;32(9):1091-105
pubmed: 15044841
Nat Commun. 2017 Sep 14;8(1):537
pubmed: 28912554
Nature. 2014 Nov 13;515(7526):274-8
pubmed: 25307057
J Biol Chem. 2018 Feb 16;293(7):2408-2421
pubmed: 29259137
Acta Neuropathol. 2001 Jun;101(6):535-9
pubmed: 11515780
Mol Neurodegener. 2012 Oct 10;7:53
pubmed: 23046583
J Neurochem. 2013 May;125(3):446-56
pubmed: 23410232
Alzheimers Dement. 2016 Oct;12(10):1033-1039
pubmed: 27154059
Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):510-4
pubmed: 24368848
Mol Neurodegener. 2015 Jul 08;10:25
pubmed: 26152284
J Neurosci Res. 2000 Feb 15;59(4):528-33
pubmed: 10679792
J Neurosci. 2002 Nov 1;22(21):9340-51
pubmed: 12417659
Proc Natl Acad Sci U S A. 1998 May 26;95(11):6469-73
pubmed: 9600990
Mol Neurodegener. 2017 Dec 22;12(1):89
pubmed: 29273078
J Neurosci Res. 1995 Oct 15;42(3):294-305
pubmed: 8583497
J Physiol. 2003 Jul 1;550(Pt 1):135-47
pubmed: 12879864
Nat Genet. 2017 Sep;49(9):1373-1384
pubmed: 28714976
Am J Pathol. 1999 Jan;154(1):255-70
pubmed: 9916940
J Parkinsons Dis. 2017;7(s1):S51-S69
pubmed: 28282814
Nat Rev Neurosci. 2016 Jan;17(1):5-21
pubmed: 26631930
Nat Rev Dis Primers. 2017 Mar 23;3:17013
pubmed: 28332488
CNS Neurol Disord Drug Targets. 2010 Aug;9(4):403-28
pubmed: 20522014
Proc Natl Acad Sci U S A. 1987 May;84(10):3410-4
pubmed: 2437579
Neuron. 2002 May 16;34(4):509-19
pubmed: 12062036
J Neurochem. 1997 Nov;69(5):2087-95
pubmed: 9349554
Mol Ther Methods Clin Dev. 2016 Apr 13;3:16026
pubmed: 27308302
J Neurosci. 2005 Jun 1;25(22):5446-54
pubmed: 15930395
J Clin Invest. 2013 May;123(5):1847-55
pubmed: 23635781
Alzheimers Res Ther. 2014 Oct 27;6(5):73
pubmed: 25580161
J Mol Neurosci. 2002 Dec;19(3):317-20
pubmed: 12540058
Nat Protoc. 2006;1(5):2452-6
pubmed: 17406491
Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2288-92
pubmed: 1706519
Prog Neurobiol. 2009 Aug;88(4):221-45
pubmed: 19552996
J Immunol. 2010 May 1;184(9):5333-43
pubmed: 20368278
Neurobiol Aging. 2009 Jan;30(1):22-33
pubmed: 17590239
Neuroscience. 2015 Oct 1;305:86-98
pubmed: 26254240
Cell Death Dis. 2017 Mar 16;8(3):e2671
pubmed: 28300838
Neurosci Lett. 1995 Apr 21;189(3):167-9
pubmed: 7624036
FASEB J. 2015 Oct;29(10):4384-98
pubmed: 26156074
Drug Discov Today. 2005 Jul 15;10(14):993-1000
pubmed: 16023058
Brain Res. 1982 Jan;255(1):3-20
pubmed: 7034866
Mol Neurodegener. 2016 Apr 27;11:33
pubmed: 27118310
Nature. 1998 Jun 18;393(6686):702-5
pubmed: 9641683
J Biol Chem. 1986 May 5;261(13):6084-9
pubmed: 3084478
J Neuroinflammation. 2012 May 31;9:115
pubmed: 22651808
Neurobiol Aging. 2013 May;34(5):1343-1354
pubmed: 23158765
Neuropathol Appl Neurobiol. 2007 Feb;33(1):43-55
pubmed: 17239007
Acta Neuropathol Commun. 2016 Feb 25;4:17
pubmed: 26916334
Neuron. 2013 Oct 16;80(2):254-6
pubmed: 24139027
Mol Cell Biol. 2000 Jun;20(11):4106-14
pubmed: 10805752
Sci Rep. 2017 Aug 7;7(1):7434
pubmed: 28785087
Ann Neurol. 2002 Mar;51(3):373-6
pubmed: 11891833
Neurobiol Dis. 2005 Oct;20(1):64-73
pubmed: 16137567
Hum Mol Genet. 2006 May 1;15(9):1483-96
pubmed: 16600994
Lancet Neurol. 2015 Aug;14(8):855-866
pubmed: 26050140
Nat Genet. 2000 Aug;25(4):402-5
pubmed: 10932182
Alzheimers Res Ther. 2014 Jan 07;6(1):3
pubmed: 24393284
J Biol Chem. 2006 Oct 6;281(40):29739-52
pubmed: 16847063
Hum Mol Genet. 2015 Sep 15;24(18):5260-9
pubmed: 26136155
Biochem Soc Trans. 2010 Aug;38(4):967-72
pubmed: 20658986