Glial fibrillary acidic protein expression alters astrocytic chemokine release and protects mice from cuprizone‐induced demyelination

Kramann, Nadine; Menken, Lena; Pförtner, Ramona; Schmid, Susanne; Stadelmann, Christine; Wegner, Christiane; Brück, Wolfgang

doi:10.1002/glia.23605

Cited by 14 publications

(10 citation statements)

References 37 publications

(51 reference statements)

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“…Glial fibrillary acidic protein belongs to a family of intermediate filament proteins that serve as a component of the cytoskeleton in astrocytes. In addition to its architectural function, recent studies revealed that the level of GFAP expression modulates astrocytic release of pro-inflammatory cytokines including Cxcl10 (Kramann et al, 2019). The expression of GFAP was found to be essential for reactive astrogliosis and glial scar formation (Pekny and Pekna, 2004).…”

Section: Discussionmentioning

confidence: 99%

Region-Specific Response of Astrocytes to Prion Infection

et al. 2019

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Chronic neuroinflammation involves reactive microgliosis and astrogliosis, and is regarded as a common pathological hallmark of neurodegenerative diseases including Alzheimer’s, Parkinson’s, ALS and prion diseases. Reactive astrogliosis, routinely observed immunohistochemically as an increase in glial fibrillary acidic protein (GFAP) signal, is a well-documented feature of chronic neuroinflammation associated with neurodegenerative diseases. Recent studies on single-cell transcriptional profiling of a mouse brain revealed that, under normal conditions, several distinct subtypes of astrocytes with regionally specialized distribution exist. However, it remains unclear whether astrocytic response to pro-inflammatory pathological conditions is uniform across whole brain or is region-specific. The current study compares the response of microglia and astrocytes to prions in mice infected with 22L mouse-adapted prion strain. While the intensity of reactive microgliosis correlated well with the extent of PrPSc deposition, reactive astrogliosis displayed a different, region-specific pattern. In particular, the thalamus and stratum oriens of hippocampus, which are both affected by 22L prions, displayed strikingly different response of astrocytes to PrPSc. Astrocytes in stratum oriens of hippocampus responded to accumulation of PrPSc with visible hypertrophy and increased GFAP, while in the thalamus, despite stronger PrPSc signal, the increase of GFAP was milder than in hippocampus, and the change in astrocyte morphology was less pronounced. The current study suggests that astrocyte response to prion infection is heterogeneous and, in part, defined by brain region. Moreover, the current work emphasizes the needs for elucidating region-specific changes in functional states of astrocytes and exploring the impact of these changes to chronic neurodegeneration.

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Section: Discussionmentioning

confidence: 99%

Region-Specific Response of Astrocytes to Prion Infection

et al. 2019

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“…Mild activation of ASTRs may induce pro-reparative A2-ASTRs, while the more reactive A1-ASTRs inhibit OPC proliferation, migration and differentiation and secrete toxic factors for OLGs [224,[231][232][233]. Notably, transgenic overexpression of GFAP alters the chemokine secretory profile of ASTRs and protects against cuprizone-induced demyelination in the corpus callosum [234], indicating that ASTR reactivity that is correlated with an upregulation of GFAP may serve a protective function. The authors did not report on differences in GM.…”

Section: Astrocyte Diversity and Remyelinationmentioning

confidence: 99%

Macroglial diversity: white and grey areas and relevance to remyelination

Werkman

Lentferink

Baron

2020

Cell. Mol. Life Sci.

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Macroglia, comprising astrocytes and oligodendroglial lineage cells, have long been regarded as uniform cell types of the central nervous system (CNS). Although regional morphological differences between these cell types were initially described after their identification a century ago, these differences were largely ignored. Recently, accumulating evidence suggests that macroglial cells form distinct populations throughout the CNS, based on both functional and morphological features. Moreover, with the use of refined techniques including single-cell and single-nucleus RNA sequencing, additional evidence is emerging for regional macroglial heterogeneity at the transcriptional level. In parallel, several studies revealed the existence of regional differences in remyelination capacity between CNS grey and white matter areas, both in experimental models for successful remyelination as well as in the chronic demyelinating disease multiple sclerosis (MS). In this review, we provide an overview of the diversity in oligodendroglial lineage cells and astrocytes from the grey and white matter, as well as their interplay in health and upon demyelination and successful remyelination. In addition, we discuss the implications of regional macroglial diversity for remyelination in light of its failure in MS. Since the etiology of MS remains unknown and only disease-modifying treatments altering the immune response are available for MS, the elucidation of macroglial diversity in grey and white matter and its putative contribution to the observed difference in remyelination efficiency between these regions may open therapeutic avenues aimed at enhancing endogenous remyelination in either area.

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“…As will be pointed out later, brain-intrinsic degenerative and/or inflammatory processes can trigger the activation of the signaling cascades involved during peripheral immune cell recruitment over the blood-brain barrier. For example, glial cells are an important source of the proinflammatory chemokines CCL2/MCP-1, RANTES and CXCL10/IP-10, which are required for TH 1 and TH 17 lymphocyte and monocyte recruitment into the CNS [28,29].…”

Section: Along Which Neuroanatomical Pathways Do Peripheral Immune Cells Travel Inside the Cns?mentioning

confidence: 99%

What Guides Peripheral Immune Cells into the Central Nervous System?

Greiner

Kipp

2021

Cells

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Multiple sclerosis (MS), an immune-mediated demyelinating disease of the central nervous system (CNS), initially presents with a relapsing-remitting disease course. During this early stage of the disease, leukocytes cross the blood–brain barrier to drive the formation of focal demyelinating plaques. Disease-modifying agents that modulate or suppress the peripheral immune system provide a therapeutic benefit during relapsing-remitting MS (RRMS). The majority of individuals with RRMS ultimately enter a secondary progressive disease stage with a progressive accumulation of neurologic deficits. The cellular and molecular basis for this transition is unclear and the role of inflammation during the secondary progressive disease stage is a subject of intense and controversial debate. In this review article, we discuss the following main hypothesis: during both disease stages, peripheral immune cells are triggered by CNS-intrinsic stimuli to invade the brain parenchyma. Furthermore, we outline the different neuroanatomical routes by which peripheral immune cells might migrate from the periphery into the CNS.

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Glial fibrillary acidic protein expression alters astrocytic chemokine release and protects mice from cuprizone‐induced demyelination

Cited by 14 publications

References 37 publications

Region-Specific Response of Astrocytes to Prion Infection

Region-Specific Response of Astrocytes to Prion Infection

Macroglial diversity: white and grey areas and relevance to remyelination

What Guides Peripheral Immune Cells into the Central Nervous System?

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