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Author Issazadehnavikas, Shohreh ♦ Kornum, Birgitte Rahbek ♦ Katsioudi, Georgia ♦ Ejlerskov, Patrick ♦ Gustafsson, Julie Ry ♦ Degn, Matilda
Source Directory of Open Access Journals (DOAJ)
Content type Text
Publisher BioMed Central
File Format HTM / HTML
Date Created 2018-08-16
Copyright Year ©2018
Language English
Subject Domain (in LCC) RC346-429
Subject Keyword Biological psychiatry ♦ Neurosciences ♦ Autoimmune neurodegeneration ♦ Internal medicine ♦ Post mitotic neurons ♦ H2 ♦ Medicine ♦ Neuropsychiatry ♦ Diseases of the nervous system ♦ DNMT1 ♦ MHC class I ♦ HLA ♦ Neurology
Abstract Abstract Major Histocompability Complex I (MHC-I) molecules present cellularly derived peptides to the adaptive immune system. Generally MHC-I is not expressed on healthy post-mitotic neurons in the central nervous system, but it is known to increase upon immune activation such as viral infections and also during neurodegenerative processes. MHC-I expression is known to be regulated by the DNA methyltransferase DNMT1 in non-neuronal cells. Interestingly DNMT1 expression is high in neurons despite these being non-dividing. This suggests a role for DNMT1 in neurons beyond the classical re-methylation of DNA after cell division. We thus investigated whether DNMT1 regulates MHC-I in post-mitotic neurons. For this we used primary cultures of mouse cerebellar granule neurons (CGNs). Our results showed that knockdown of DNMT1 in CGNs caused upregulation of some, but not all subtypes of MHC-I genes. This effect was synergistically enhanced by subsequent IFNγ treatment. Overall MHC-I protein level was not affected by knockdown of DNMT1 in CGNs. Instead our results show that the relative MHC-I expression levels among the different MHC subtypes is regulated by DNMT1 activity. In conclusion, we show that while the mouse H2-D1/L alleles are suppressed in neurons by DNMT1 activity under normal circumstances, the H2-K1 allele is not. This finding is particularly important in two instances. One: in the context of CNS autoimmunity with epitope presentation by specific MHC-I subtypes where this allele specific regulation might become important; and two: in amyotropic lateral sclerosis (ALS) where H2-K but not H2-D protects motor neurons from ALS astrocyte-induced toxicity in a mouse model of ALS.
ISSN 17566606
Age Range 18 to 22 years ♦ above 22 year
Educational Use Research
Education Level UG and PG ♦ Career/Technical Study
Learning Resource Type Article
Publisher Date 2018-07-01
e-ISSN 17566606
Journal Molecular Brain
Volume Number 11
Issue Number 1
Page Count 16
Starting Page 1
Ending Page 16


Source: Directory of Open Access Journals (DOAJ)