Effect of Mycobacterium leprae on neurotrophins expression in human Schwann cells and mouse sciatic nerves.
Journal
Memorias do Instituto Oswaldo Cruz
ISSN: 1678-8060
Titre abrégé: Mem Inst Oswaldo Cruz
Pays: Brazil
ID NLM: 7502619
Informations de publication
Date de publication:
2020
2020
Historique:
received:
20
02
2020
accepted:
25
06
2020
entrez:
23
7
2020
pubmed:
23
7
2020
medline:
28
7
2020
Statut:
ppublish
Résumé
Although Mycobacterium leprae (ML) is well characterised as the causative agent of leprosy, the pathophysiological mechanisms underlying peripheral nerve damage still need further understanding. In vitro and in vivo studies have yielded insights into molecular mechanisms of ML interaction with Schwann cells (SC), indicating the regulation of genes and proteins crucial to neural plasticity. We aimed to investigate the effect of ML on neurotrophins expression in human SC (hSC) and mice sciatic nerves to better understand their role in leprosy neuropathy, and aiming to contribute to future therapeutic approaches. We evaluated mRNA and protein expression of BDNF, NGF, NT-3, NT-4 in hSC from amputation nerve fragments, as well as in athymic nude mice, infected by ML for eight months. Our in vitro results showed a trend to decline in NGF and BDNF mRNA in ML-treated hSC, compared to controls. The immunodetection of BDNF and NT-4 was significantly downregulated in ML-treated hSC. Conversely, ML-infected mice demonstrated upregulation of NT-3, compared to non-infected animals. Our findings indicate that ML may be involved in neurotrophins regulation, suggesting that a pathogen-related imbalance of these growth factors may have a role in the neural impairment of leprosy.
Sections du résumé
BACKGROUND
BACKGROUND
Although Mycobacterium leprae (ML) is well characterised as the causative agent of leprosy, the pathophysiological mechanisms underlying peripheral nerve damage still need further understanding. In vitro and in vivo studies have yielded insights into molecular mechanisms of ML interaction with Schwann cells (SC), indicating the regulation of genes and proteins crucial to neural plasticity.
OBJECTIVES
OBJECTIVE
We aimed to investigate the effect of ML on neurotrophins expression in human SC (hSC) and mice sciatic nerves to better understand their role in leprosy neuropathy, and aiming to contribute to future therapeutic approaches.
METHODS
METHODS
We evaluated mRNA and protein expression of BDNF, NGF, NT-3, NT-4 in hSC from amputation nerve fragments, as well as in athymic nude mice, infected by ML for eight months.
FINDINGS AND MAIN CONCLUSIONS
CONCLUSIONS
Our in vitro results showed a trend to decline in NGF and BDNF mRNA in ML-treated hSC, compared to controls. The immunodetection of BDNF and NT-4 was significantly downregulated in ML-treated hSC. Conversely, ML-infected mice demonstrated upregulation of NT-3, compared to non-infected animals. Our findings indicate that ML may be involved in neurotrophins regulation, suggesting that a pathogen-related imbalance of these growth factors may have a role in the neural impairment of leprosy.
Identifiants
pubmed: 32696914
pii: S0074-02762020000100330
doi: 10.1590/0074-02760200075
pmc: PMC7367213
pii:
doi:
Substances chimiques
Nerve Growth Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e200075Références
Methods Mol Biol. 2018;1727:1-17
pubmed: 29222769
Nature. 1989 Sep 14;341(6238):149-52
pubmed: 2779653
Science. 1998 Dec 11;282(5396):2076-9
pubmed: 9851927
Neuron. 2004 Jul 22;43(2):183-91
pubmed: 15260955
Clin Sci (Lond). 2006 Feb;110(2):175-91
pubmed: 16411894
Arq Neuropsiquiatr. 2011 Feb;69(1):100-4
pubmed: 21359431
J Vis Exp. 2014 Mar 23;(85):
pubmed: 24686247
Science. 1987 Sep 4;237(4819):1154-62
pubmed: 3306916
J Neuroimmunol. 2013 Oct 15;263(1-2):83-90
pubmed: 23993653
Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14661-8
pubmed: 11717413
Front Immunol. 2018 May 07;9:939
pubmed: 29867937
Microbiol Spectr. 2019 Jul;7(4):
pubmed: 31322104
Pain. 2000 Mar;85(1-2):231-8
pubmed: 10692623
Clin Dermatol. 2015 Jan-Feb;33(1):46-54
pubmed: 25432810
Neurosci Lett. 1995 Nov 10;200(1):37-40
pubmed: 8584261
Med Sci Monit. 2018 Aug 26;24:5943-5950
pubmed: 30145601
Trends Biotechnol. 1995 Jun;13(6):217-27
pubmed: 7598845
Neuroscience. 2001;105(3):779-83
pubmed: 11516841
J Neurosci Res. 2007 Oct;85(13):2863-9
pubmed: 17628499
J Cell Biol. 1992 Oct;119(1):45-54
pubmed: 1527172
J Neurosci. 2006 Jun 14;26(24):6651-60
pubmed: 16775154
Mol Neurobiol. 2018 Apr;55(4):2840-2850
pubmed: 28455697
Neuropathol Appl Neurobiol. 1997 Feb;23(1):59-67
pubmed: 9061691
Cold Spring Harb Perspect Biol. 2015 May 08;7(7):a020487
pubmed: 25957303
Lepr Rev. 2009 Dec;80(4):388-401
pubmed: 20306637
J Neurocytol. 1990 Jun;19(3):432-42
pubmed: 2391542
Philos Trans R Soc Lond B Biol Sci. 2006 Sep 29;361(1473):1545-64
pubmed: 16939974
J Neurosci Res. 1997 Oct 15;50(2):291-9
pubmed: 9373038
J Hand Surg Am. 2019 May;44(5):411-415
pubmed: 30177357
Mol Neurobiol. 2014 Dec;50(3):945-70
pubmed: 24752592