Cover Image

Evaluation of the effective time for GSK-3 inhibition in experimental autoimmune encephalomyelitis mouse model by tideglusib (NP-12) in preventing neuroinflammation

Glycogen synthase kinase-3 (GSK-3) is an enzyme involved in various neurodegenerative and neuro-inflammatory diseases, including multiple sclerosis (MS) and its animal model of experimental autoimmune encephalomyelitis (EAE). The severity of the disease could be characterized by the degree of cel...

Full description

Saved in:
Bibliographic Details
Main Author: Al-Zaidi, Ahmed Salam
Format: Thesis
Language:English
Published: 2018
Subjects:
Encephalomyelitis
Encephalitis
Online Access:http://psasir.upm.edu.my/id/eprint/84211/1/FPSK%20%28m%29%202019%2033%20UPM%20ir.pdf
http://psasir.upm.edu.my/id/eprint/84211/
Tags: Add Tag
No Tags, Be the first to tag this record!
id my.upm.eprints.84211
record_format eprints
spelling my.upm.eprints.842112022-01-04T02:35:57Z http://psasir.upm.edu.my/id/eprint/84211/ Evaluation of the effective time for GSK-3 inhibition in experimental autoimmune encephalomyelitis mouse model by tideglusib (NP-12) in preventing neuroinflammation Al-Zaidi, Ahmed Salam Glycogen synthase kinase-3 (GSK-3) is an enzyme involved in various neurodegenerative and neuro-inflammatory diseases, including multiple sclerosis (MS) and its animal model of experimental autoimmune encephalomyelitis (EAE). The severity of the disease could be characterized by the degree of cellular invasion to the central nervous system (CNS) and demyelination that partly mediated by Th1 and Th17 effector cells. The present study is to investigate the efficacy of GSK-3 inhibition at a different course of treatment in ameliorating disease progression. This study also aims to evaluate the effects of GSK-3 inhibition to central neuro-invasion and demyelination. Female C57BL/6 mice were induced with myelin oligodendrocyte glycoprotein (MOG35-55) in conjunction with complete freund's adjuvant (CFA) and pertussis toxin. Inhibition of GSK-3 is performed by the administration of NP-12, a small heterocyclic Thiadiazolidinones (TDZD), intraperitoneally during pre-EAE induction, on the same day, and post-EAE. Data revealed that NP-12 delivery during pre-EAE induction greatly protected the mice from EAE, delayed the onset of EAE symptoms by 7 days from day-14.3 ± 0.5 (in EAE mice) until day-21.3 ± 3.2 (in the treated mice). Furthermore, NP-12 treated-EAE mice had notably reduced the inflammatory cells infiltration and axonal damage (demyelination) in the spinal cord. Inhibition of GSK-3 also abrogated the production of Th1, Th9 and Th17 associated cytokines but, increases the production of IL-4 level to 1790 ± 95.0 pg/mL compare to EAE 480 ± 38.0 pg/mL and in IL-10 780 ± 22.0 pg/mL compared to EAE 410 ± 16.0 pg/mL. These data demonstrate the effectiveness of NP-12 at a different time course of administration to reduce the severity of EAE disease and protect the CNS environment from potential cellular invasion or demyelination, thus, suggests the potential use of GSK-3 inhibitor in the treatment of EAE. 2018-12 Thesis NonPeerReviewed text en http://psasir.upm.edu.my/id/eprint/84211/1/FPSK%20%28m%29%202019%2033%20UPM%20ir.pdf Al-Zaidi, Ahmed Salam (2018) Evaluation of the effective time for GSK-3 inhibition in experimental autoimmune encephalomyelitis mouse model by tideglusib (NP-12) in preventing neuroinflammation. Masters thesis, Universiti Putra Malaysia. Encephalomyelitis Encephalitis
institution Universiti Putra Malaysia
building UPM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Putra Malaysia
content_source UPM Institutional Repository
url_provider http://psasir.upm.edu.my/
language English
topic Encephalomyelitis
Encephalitis
spellingShingle Encephalomyelitis
Encephalitis
Al-Zaidi, Ahmed Salam
Evaluation of the effective time for GSK-3 inhibition in experimental autoimmune encephalomyelitis mouse model by tideglusib (NP-12) in preventing neuroinflammation
description Glycogen synthase kinase-3 (GSK-3) is an enzyme involved in various neurodegenerative and neuro-inflammatory diseases, including multiple sclerosis (MS) and its animal model of experimental autoimmune encephalomyelitis (EAE). The severity of the disease could be characterized by the degree of cellular invasion to the central nervous system (CNS) and demyelination that partly mediated by Th1 and Th17 effector cells. The present study is to investigate the efficacy of GSK-3 inhibition at a different course of treatment in ameliorating disease progression. This study also aims to evaluate the effects of GSK-3 inhibition to central neuro-invasion and demyelination. Female C57BL/6 mice were induced with myelin oligodendrocyte glycoprotein (MOG35-55) in conjunction with complete freund's adjuvant (CFA) and pertussis toxin. Inhibition of GSK-3 is performed by the administration of NP-12, a small heterocyclic Thiadiazolidinones (TDZD), intraperitoneally during pre-EAE induction, on the same day, and post-EAE. Data revealed that NP-12 delivery during pre-EAE induction greatly protected the mice from EAE, delayed the onset of EAE symptoms by 7 days from day-14.3 ± 0.5 (in EAE mice) until day-21.3 ± 3.2 (in the treated mice). Furthermore, NP-12 treated-EAE mice had notably reduced the inflammatory cells infiltration and axonal damage (demyelination) in the spinal cord. Inhibition of GSK-3 also abrogated the production of Th1, Th9 and Th17 associated cytokines but, increases the production of IL-4 level to 1790 ± 95.0 pg/mL compare to EAE 480 ± 38.0 pg/mL and in IL-10 780 ± 22.0 pg/mL compared to EAE 410 ± 16.0 pg/mL. These data demonstrate the effectiveness of NP-12 at a different time course of administration to reduce the severity of EAE disease and protect the CNS environment from potential cellular invasion or demyelination, thus, suggests the potential use of GSK-3 inhibitor in the treatment of EAE.
format Thesis
author Al-Zaidi, Ahmed Salam
author_facet Al-Zaidi, Ahmed Salam
author_sort Al-Zaidi, Ahmed Salam
title Evaluation of the effective time for GSK-3 inhibition in experimental autoimmune encephalomyelitis mouse model by tideglusib (NP-12) in preventing neuroinflammation
title_short Evaluation of the effective time for GSK-3 inhibition in experimental autoimmune encephalomyelitis mouse model by tideglusib (NP-12) in preventing neuroinflammation
title_full Evaluation of the effective time for GSK-3 inhibition in experimental autoimmune encephalomyelitis mouse model by tideglusib (NP-12) in preventing neuroinflammation
title_fullStr Evaluation of the effective time for GSK-3 inhibition in experimental autoimmune encephalomyelitis mouse model by tideglusib (NP-12) in preventing neuroinflammation
title_full_unstemmed Evaluation of the effective time for GSK-3 inhibition in experimental autoimmune encephalomyelitis mouse model by tideglusib (NP-12) in preventing neuroinflammation
title_sort evaluation of the effective time for gsk-3 inhibition in experimental autoimmune encephalomyelitis mouse model by tideglusib (np-12) in preventing neuroinflammation
publishDate 2018
url http://psasir.upm.edu.my/id/eprint/84211/1/FPSK%20%28m%29%202019%2033%20UPM%20ir.pdf
http://psasir.upm.edu.my/id/eprint/84211/
_version_ 1724075421523247104
score 13.211869

Similar Items