Characterizing microglial gene expression in a model of secondary progressive multiple sclerosis
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Characterizing microglial gene expression in a model of secondary progressive multiple sclerosis. / Vainchtein, Ilia D.; Alsema, Astrid M.; Dubbelaar, Marissa L.; Grit, Corien; Vinet, Jonathan; van Weering, Hilmar R. J.; Al-Izki, Sarah; Biagini, Giuseppe; Brouwer, Nieske; Amor, Sandra; Baker, David; Eggen, Bart J. L.; Boddeke, Erik W. G. M.; Kooistra, Susanne M.
I: Glia, Bind 71, Nr. 3, 2023, s. 588-601.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Characterizing microglial gene expression in a model of secondary progressive multiple sclerosis
AU - Vainchtein, Ilia D.
AU - Alsema, Astrid M.
AU - Dubbelaar, Marissa L.
AU - Grit, Corien
AU - Vinet, Jonathan
AU - van Weering, Hilmar R. J.
AU - Al-Izki, Sarah
AU - Biagini, Giuseppe
AU - Brouwer, Nieske
AU - Amor, Sandra
AU - Baker, David
AU - Eggen, Bart J. L.
AU - Boddeke, Erik W. G. M.
AU - Kooistra, Susanne M.
PY - 2023
Y1 - 2023
N2 - Multiple sclerosis (MS) is the most common inflammatory, demyelinating and neurodegenerative disease of the central nervous system in young adults. Chronic-relapsing experimental autoimmune encephalomyelitis (crEAE) in Biozzi ABH mice is an experimental model of MS. This crEAE model is characterized by an acute phase with severe neurological disability, followed by remission of disease, relapse of neurological disease and remission that eventually results in a chronic progressive phase that mimics the secondary progressive phase (SPEAE) of MS. In both MS and SPEAE, the role of microglia is poorly defined. We used a crEAE model to characterize microglia in the different phases of crEAE phases using morphometric and RNA sequencing analyses. At the initial, acute inflammation phase, microglia acquired a pro-inflammatory phenotype. At the remission phase, expression of standard immune activation genes was decreased while expression of genes associated with lipid metabolism and tissue remodeling were increased. Chronic phase microglia partially regain inflammatory gene sets and increase expression of genes associated with proliferation. Together, the data presented here indicate that microglia obtain different features at different stages of crEAE and a particularly mixed phenotype in the chronic stage. Understanding the properties of microglia that are present at the chronic phase of EAE will help to understand the role of microglia in secondary progressive MS, to better aid the development of therapies for this phase of the disease.
AB - Multiple sclerosis (MS) is the most common inflammatory, demyelinating and neurodegenerative disease of the central nervous system in young adults. Chronic-relapsing experimental autoimmune encephalomyelitis (crEAE) in Biozzi ABH mice is an experimental model of MS. This crEAE model is characterized by an acute phase with severe neurological disability, followed by remission of disease, relapse of neurological disease and remission that eventually results in a chronic progressive phase that mimics the secondary progressive phase (SPEAE) of MS. In both MS and SPEAE, the role of microglia is poorly defined. We used a crEAE model to characterize microglia in the different phases of crEAE phases using morphometric and RNA sequencing analyses. At the initial, acute inflammation phase, microglia acquired a pro-inflammatory phenotype. At the remission phase, expression of standard immune activation genes was decreased while expression of genes associated with lipid metabolism and tissue remodeling were increased. Chronic phase microglia partially regain inflammatory gene sets and increase expression of genes associated with proliferation. Together, the data presented here indicate that microglia obtain different features at different stages of crEAE and a particularly mixed phenotype in the chronic stage. Understanding the properties of microglia that are present at the chronic phase of EAE will help to understand the role of microglia in secondary progressive MS, to better aid the development of therapies for this phase of the disease.
KW - experimental autoimmune encephalitis
KW - microglia
KW - RNA sequencing
KW - secondary progressive MS
KW - EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS
KW - EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS
KW - OSTEOPONTIN LEVELS
KW - DISEASE-ACTIVITY
KW - ANIMAL-MODELS
KW - SPINAL-CORD
KW - REMYELINATION
KW - IMMUNE
KW - MYELIN
KW - ACTIVATION
U2 - 10.1002/glia.24297
DO - 10.1002/glia.24297
M3 - Journal article
C2 - 36377669
VL - 71
SP - 588
EP - 601
JO - GLIA
JF - GLIA
SN - 0894-1491
IS - 3
ER -
ID: 327944309