Please use this identifier to cite or link to this item:
https://hdl.handle.net/11147/10421
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Akyıldız Demir, Seçil | - |
dc.contributor.author | Timur, Zehra Kevser | - |
dc.contributor.author | Ateş, Nurselin | - |
dc.contributor.author | Martinez, Luis Alarcon | - |
dc.contributor.author | Seyrantepe, Volkan | - |
dc.date.accessioned | 2021-01-24T18:43:08Z | - |
dc.date.available | 2021-01-24T18:43:08Z | - |
dc.date.issued | 2020 | - |
dc.identifier.issn | 1742-2094 | - |
dc.identifier.uri | https://doi.org/10.1186/s12974-020-01947-6 | - |
dc.identifier.uri | https://hdl.handle.net/11147/10421 | - |
dc.description.abstract | Background Tay-Sachs disease (TSD), a type of GM2-gangliosidosis, is a progressive neurodegenerative lysosomal storage disorder caused by mutations in the alpha subunit of the lysosomal beta-hexosaminidase enzyme. This disease is characterized by excessive accumulation of GM2 ganglioside, predominantly in the central nervous system. Although Tay-Sachs patients appear normal at birth, the progressive accumulation of undegraded GM2 gangliosides in neurons leads to death. Recently, an early onset Tay-Sachs disease mouse model, with genotypeHexa-/-Neu3-/-, was generated. Progressive accumulation of GM2 led to premature death of the double KO mice. Importantly, this double-deficient mouse model displays typical features of Tay-Sachs patients, such as cytoplasmic vacuolization of nerve cells, deterioration of Purkinje cells, neuronal death, deceleration in movement, ataxia, and tremors. GM2-gangliosidosis is characterized by acute neurodegeneration preceded by activated microglia expansion, macrophage, and astrocyte activation, along with the production of inflammatory mediators. However, the mechanism of disease progression inHexa-/-Neu3-/-mice, relevant to neuroinflammation is poorly understood. Method In this study, we investigated the onset and progression of neuroinflammatory changes in the cortex, cerebellum, and retina ofHexa-/-Neu3-/-mice and control littermates by using a combination of molecular genetics and immunochemical procedures. Results We found elevated levels of pro-inflammatory cytokine and chemokine transcripts, such as Ccl2, Ccl3, Ccl4, and Cxcl10 and also extensive microglial and astrocyte activation and proliferation, accompanied by peripheral blood mononuclear cell infiltration in the vicinity of neurons and oligodendrocytes. Behavioral tests demonstrated a high level of anxiety, and age-dependent loss in both spatial learning and fear memory inHexa-/-Neu3-/-mice compared with that in the controls. Conclusion Altogether, our data suggest thatHexa-/-Neu3-/-mice display a phenotype similar to Tay-Sachs patients suffering from chronic neuroinflammation triggered by GM2 accumulation. Furthermore, our work contributes to better understanding of the neuropathology in a mouse model of early onset Tay-Sachs disease. | en_US |
dc.description.sponsorship | This study was partially supported by EMBO 2010 Installation Grant to Prof Dr. Volkan Seyrantepe. | en_US |
dc.language.iso | en | en_US |
dc.publisher | BioMed Central Ltd. | en_US |
dc.relation.ispartof | Journal of Neuroinflammation | en_US |
dc.rights | info:eu-repo/semantics/openAccess | en_US |
dc.subject | Tay-Sachs disease | en_US |
dc.subject | GM2 | en_US |
dc.subject | Mouse model | en_US |
dc.subject | Neuroinflammation | en_US |
dc.subject | Behavior | en_US |
dc.title | GM2 ganglioside accumulation causes neuroinflammation and behavioral alterations in a mouse model of early onset Tay-Sachs disease | en_US |
dc.type | Article | en_US |
dc.institutionauthor | Demir, Seçil Akyıldız | - |
dc.institutionauthor | Timur, Zehra Kevser | - |
dc.institutionauthor | Ateş, Nurselin | - |
dc.institutionauthor | Seyrantepe, Volkan | - |
dc.department | İzmir Institute of Technology. Molecular Biology and Genetics | en_US |
dc.identifier.volume | 17 | en_US |
dc.identifier.issue | 1 | en_US |
dc.identifier.wos | WOS:000574340600004 | en_US |
dc.identifier.scopus | 2-s2.0-85091264810 | en_US |
dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı | en_US |
dc.identifier.doi | 10.1186/s12974-020-01947-6 | - |
dc.identifier.pmid | 32951593 | en_US |
dc.relation.doi | 10.1186/s12974-020-01947-6 | en_US |
dc.coverage.doi | 10.1186/s12974-020-01947-6 | en_US |
local.message.claim | 2022-06-15T16:35:36.089+0300 | * |
local.message.claim | |rp02635 | * |
local.message.claim | |submit_approve | * |
local.message.claim | |dc_contributor_author | * |
local.message.claim | |None | * |
dc.identifier.wosquality | Q1 | - |
dc.identifier.scopusquality | Q1 | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.grantfulltext | open | - |
item.openairetype | Article | - |
item.cerifentitytype | Publications | - |
item.fulltext | With Fulltext | - |
item.languageiso639-1 | en | - |
crisitem.author.dept | 01.01. Units Affiliated to the Rectorate | - |
crisitem.author.dept | 04.03. Department of Molecular Biology and Genetics | - |
crisitem.author.dept | 04.03. Department of Molecular Biology and Genetics | - |
Appears in Collections: | Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection |
Files in This Item:
File | Size | Format | |
---|---|---|---|
s12974-020-01947-6.pdf | 12.83 MB | Adobe PDF | View/Open |
CORE Recommender
SCOPUSTM
Citations
23
checked on Dec 6, 2024
WEB OF SCIENCETM
Citations
21
checked on Dec 7, 2024
Page view(s)
438
checked on Dec 9, 2024
Download(s)
210
checked on Dec 9, 2024
Google ScholarTM
Check
Altmetric
Items in GCRIS Repository are protected by copyright, with all rights reserved, unless otherwise indicated.