Parkinson's disease relevant pathological features are manifested in male Pink1/Parkin deficient rats.
Alpha-synuclein
Motor symptoms
Neurodegeneration
Parkin/Pink1
T cells
Tremor
Journal
Brain, behavior, & immunity - health
ISSN: 2666-3546
Titre abrégé: Brain Behav Immun Health
Pays: United States
ID NLM: 101759062
Informations de publication
Date de publication:
Aug 2023
Aug 2023
Historique:
received:
14
06
2023
accepted:
15
06
2023
medline:
24
7
2023
pubmed:
24
7
2023
entrez:
24
7
2023
Statut:
epublish
Résumé
Animal disease models are important for neuroscience experimentation and in the study of neurodegenerative disorders. The major neurodegenerative disorder leading to motor impairments is Parkinson's disease (PD). The identification of hereditary forms of PD uncovered gene mutations and variants, such as loss-of-function mutations in PTEN-induced putative kinase 1 (Pink1) and the E3 ubiquitin ligase Parkin, two proteins involved in mitochondrial quality control, that could be harnessed to create animal models. However, to date, such models have not reproducibly recapitulated major aspects of the disease. Here, we describe the generation and phenotypic characterization of a combined Pink1/Parkin double knockout (dKO) rat, which reproducibly exhibits PD-relevant abnormalities, particularly in male animals. Motor dysfunction in Pink1/Parkin dKO rats was characterized by gait abnormalities and decreased rearing frequency, the latter of which was responsive to levodopa treatment. Pink1/Parkin dKO rats exhibited elevated plasma levels of neurofilament light chain and significant loss of tyrosine hydroxylase expression in the substantia nigra pars compacta (SNpc). Glial cell activation was also observed in the SNpc. Pink1/Parkin dKO rats showed elevated plasma and reduced cerebrospinal levels of alpha-synuclein as well as the presence of alpha-synuclein aggregates in the striatum. Further, the profile of circulating lymphocytes was altered, as elevated CD3
Identifiants
pubmed: 37484197
doi: 10.1016/j.bbih.2023.100656
pii: S2666-3546(23)00070-4
pmc: PMC10362548
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100656Informations de copyright
© 2023 The Authors.
Déclaration de conflit d'intérêts
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Références
J Neurochem. 2009 Nov;111(3):696-702
pubmed: 19694908
Eur Arch Psychiatry Clin Neurosci. 2014 Jun;264(4):357-62
pubmed: 24374936
Sci Rep. 2021 Jan 12;11(1):752
pubmed: 33436993
J Neuroimmunol. 2013 Dec 15;265(1-2):1-10
pubmed: 24210793
Cold Spring Harb Perspect Med. 2012 Jan;2(1):a008888
pubmed: 22315721
Proc Natl Acad Sci U S A. 2007 Jul 3;104(27):11441-6
pubmed: 17563363
Curr Biol. 2018 Feb 19;28(4):R170-R185
pubmed: 29462587
J Vis Exp. 2021 Jan 18;(167):
pubmed: 33522500
Parkinsonism Relat Disord. 2019 Mar;60:25-31
pubmed: 30404763
Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10744-9
pubmed: 15249681
Pflugers Arch. 2019 Oct;471(10):1247-1261
pubmed: 31520182
Parkinsonism Relat Disord. 2021 Jun;87:41-47
pubmed: 33964785
Indian J Med Res. 2017 Dec;146(6):738-745
pubmed: 29664032
Blood Cells Mol Dis. 2018 Nov;73:33-37
pubmed: 30195626
Front Med (Lausanne). 2021 Oct 18;8:736978
pubmed: 34733860
Mov Disord. 2018 Oct;33(10):1580-1590
pubmed: 30294923
Neurology. 2008 May 20;70(21):e87
pubmed: 18490612
Mol Ther. 2022 Apr 6;30(4):1465-1483
pubmed: 35038583
Proc Natl Acad Sci U S A. 2004 Jun 22;101(25):9435-40
pubmed: 15197276
Proc Natl Acad Sci U S A. 2005 May 31;102(22):8024-9
pubmed: 15911761
Nature. 2018 Sep;561(7722):258-262
pubmed: 30135585
J Neurosci. 2013 Jun 5;33(23):9592-600
pubmed: 23739956
Neurology. 2017 Mar 7;88(10):930-937
pubmed: 28179466
Mov Disord. 2017 Nov;32(11):1504-1523
pubmed: 29124790
EMBO J. 2012 Jun 26;31(14):3038-62
pubmed: 22735187
Brain Commun. 2019;1(1):fcz016
pubmed: 31667474
Mol Neurobiol. 2016 Jan;53(1):171-186
pubmed: 25421206
PLoS One. 2009 Jun 03;4(6):e5777
pubmed: 19492057
Neuroepidemiology. 2016;46(4):292-300
pubmed: 27105081
Front Neurosci. 2019 Jan 09;12:1034
pubmed: 30686993
Curr Gerontol Geriatr Res. 2013;2013:986254
pubmed: 24382959
BMC Biol. 2015 Jul 22;13:50
pubmed: 26197889
Brain Commun. 2021 Apr 23;3(2):fcab077
pubmed: 33928251
Front Neurol. 2020 Jul 28;11:682
pubmed: 32849182
Front Aging Neurosci. 2021 Aug 02;13:716993
pubmed: 34408647
Front Neurol. 2018 Aug 03;9:628
pubmed: 30123178
J Neurol Sci. 2016 Nov 15;370:256-257
pubmed: 27772770
Behav Brain Res. 2022 Jan 24;417:113575
pubmed: 34534596
Metabolism. 2015 Mar;64(3 Suppl 1):S40-6
pubmed: 25510818
Brain Pathol. 2014 Mar;24(2):152-65
pubmed: 24033473
Sci Rep. 2017 Jun 12;7(1):3225
pubmed: 28607434
Brain. 1993 Dec;116 ( Pt 6):1451-63
pubmed: 8293280
Sci Rep. 2020 Jun 17;10(1):9820
pubmed: 32555260
Neurodegener Dis. 2012;10(1-4):277-84
pubmed: 22205172
Brain. 2010 Apr;133(Pt 4):1128-42
pubmed: 20356854
Cells. 2021 Jan 31;10(2):
pubmed: 33572534
Front Neurol. 2020 Jan 21;10:1388
pubmed: 32038461
Hum Mol Genet. 2003 Sep 15;12(18):2277-91
pubmed: 12915482
Mov Disord. 2021 Jan;36(1):25-36
pubmed: 33314312
Mov Disord. 2008 Jul 30;23(10):1461-5
pubmed: 18546294
NPJ Parkinsons Dis. 2020 Nov 13;6(1):33
pubmed: 33298969
Neuroscience. 2019 Jun 15;409:169-179
pubmed: 31029729
J Clin Invest. 2009 Jan;119(1):182-92
pubmed: 19104149
Nature. 2006 Jun 29;441(7097):1162-6
pubmed: 16672981
Nature. 2006 Jun 29;441(7097):1157-61
pubmed: 16672980
Acta Neuropathol Commun. 2014 Aug 07;2:90
pubmed: 25099483
J Neural Transm (Vienna). 1999;106(7-8):685-92
pubmed: 10907727
J Neurol Neurosurg Psychiatry. 2017 Oct;88(10):818-824
pubmed: 28550072
Nature. 2017 Jun 29;546(7660):656-661
pubmed: 28636593
Ann Neurol. 1995 Jun;37(6):714-22
pubmed: 7778844
Neurochem Int. 2017 Oct;109:106-116
pubmed: 28434973
Eur J Immunol. 2013 Dec;43(12):3355-60
pubmed: 24037540
J Thromb Thrombolysis. 2022 May;53(4):950-953
pubmed: 34797472
Mov Disord. 2018 Nov;33(11):1724-1733
pubmed: 30440090
Neurobiol Dis. 2020 Oct;144:105028
pubmed: 32736085
Ann Neurol. 2015 Mar;77(3):458-68
pubmed: 25558820
Neuropathology. 2018 Mar 26;:
pubmed: 29582466
Sci Rep. 2018 Nov 26;8(1):17368
pubmed: 30478269
J Neural Transm (Vienna). 2010 Sep;117(9):1093-8
pubmed: 20665056
Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):4078-83
pubmed: 12642658
Front Aging Neurosci. 2021 Sep 22;13:717930
pubmed: 34630068
Nat Commun. 2020 Apr 20;11(1):1875
pubmed: 32313102
Arch Phys Med Rehabil. 2011 Sep;92(9):1431-6
pubmed: 21878213
Neurobiol Dis. 2014 Oct;70:190-203
pubmed: 24969022
NPJ Parkinsons Dis. 2021 Oct 11;7(1):93
pubmed: 34635674
J Neurosci Res. 2015 Nov;93(11):1713-27
pubmed: 26234713
J Biol Chem. 2003 Oct 31;278(44):43628-35
pubmed: 12930822
J Alzheimers Dis. 2021;82(3):913-919
pubmed: 34151807
Neurobiol Learn Mem. 1996 Mar;65(2):135-53
pubmed: 8833103
Nature. 2019 Jul;571(7766):565-569
pubmed: 31316206
Mol Neurobiol. 2016 Apr;53(3):1625-1636
pubmed: 25676140
Neurology. 2020 Aug 18;95(7):e827-e838
pubmed: 32680941
PLoS One. 2016 Jan 14;11(1):e0142520
pubmed: 26764486