English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
 
 
DownloadE-Mail
  Liver kinase B1 depletion from astrocytes worsens disease in a mouse model of multiple sclerosis

Kalinin, S., Meares, G. P., Lin, S. X., Pietruczyk, E. A., Saher, G., Spieth, L., et al. (2020). Liver kinase B1 depletion from astrocytes worsens disease in a mouse model of multiple sclerosis. Glia, 68(3), 600-616. doi:10.1002/glia.23742.

Item is

Files

show Files
hide Files
:
3374333.pdf (Publisher version), 7MB
 
File Permalink:
-
Name:
3374333.pdf
Description:
-
OA-Status:
Visibility:
Restricted (Max Planck Institute for Multidisciplinary Sciences, MGMN; )
MIME-Type / Checksum:
application/pdf
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show

Creators

show
hide
 Creators:
Kalinin, S., Author
Meares, G. P., Author
Lin, S. X., Author
Pietruczyk, E. A., Author
Saher, G.1, Author           
Spieth, L.1, Author           
Nave, K.-A.1, Author           
Boullerne, A. I., Author
Lutz, S. E., Author
Benveniste, E. N., Author
Feinstein, D. L., Author
Affiliations:
1Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society, ou_2173664              

Content

show
hide
Free keywords: EAE; astrocyte; liver kinase B1; mitochondria; motor neuron; multiple sclerosis.
 Abstract: Liver kinase B1 (LKB1) is a ubiquitously expressed kinase involved in the regulation
of cell metabolism, growth, and inflammatory activation. We previously reported that
a single nucleotide polymorphism in the gene encoding LKB1 is a risk factor for multi-
ple sclerosis (MS). Since astrocyte activation and metabolic function have important
roles in regulating neuroinflammation and neuropathology, we examined the serine/
threonine kinase LKB1 in astrocytes in a chronic experimental autoimmune encepha-
lomyelitis mouse model of MS. To reduce LKB1, a heterozygous astrocyte-selective
conditional knockout (het-cKO) model was used. While disease incidence was similar,
disease severity was worsened in het-cKO mice. RNAseq analysis identified Kyoto
Encyclopedia of Genes and Genomes (KEGG) pathways enriched in het-cKO mice
relating to mitochondrial function, confirmed by alterations in mitochondrial complex
proteins and reductions in mRNAs related to astrocyte metabolism. Enriched path-
ways included major histocompatibility class II genes, confirmed by increases in
MHCII protein in spinal cord and cerebellum of het-cKO mice. We observed
increased numbers of CD4+ Th17 cells and increased neuronal damage in spinal
cords of het-cKO mice, associated with reduced expression of choline
acetyltransferase, accumulation of immunoglobulin-γ, and reduced expression of fac-
tors involved in motor neuron survival. In vitro, LKB1-deficient astrocytes showed
reduced metabolic function and increased inflammatory activation. These data sug-
gest that metabolic dysfunction in astrocytes, in this case due to LKB1 deficiency,
can exacerbate demyelinating disease by loss of metabolic support and increase in
the inflammatory environment.

Details

show
hide
Language(s): eng - English
 Dates: 2019-10-052019-10-302020-03
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1002/glia.23742
 Degree: -

Event

show

Legal Case

show

Project information

show hide
Project name : This work was supported by grants BX002625 and 14S-RCS- 003 from the Department of Veterans Affairs (D.L.F.); grant TA3050-A-1 from the National Multiple Sclerosis Society (G.P.M.), grant R01 NS057563 (E.N.B.), and grant KL2TR002002 from the NIH (S.E.L.)
Grant ID : -
Funding program : -
Funding organization : -

Source 1

show
hide
Title: Glia
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 68 (3) Sequence Number: - Start / End Page: 600 - 616 Identifier: ISSN: 0894-1491
ISSN: 1098-1136