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Brain-Region-Specific Astroglial Responses In Vitro After LPS Exposure

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Abstract

Astroglia is well-known to be integrated in the complex regulation of neuroinflammation in the central nervous system. Astrocytes become activated and synthesize cytokines, chemokines, and prostanoids during degenerative and vulnerable processes and interact with other immune-competent cells. Degenerative disorders often occur in a brain-region-specific fashion suggesting differences in the activity and reactivity of innate immune cells. We have investigated the potency of lipopolysaccharides (LPS) to differently stimulate astrocytes from the cortex and midbrain. Astroglial cultures were prepared from Bagg albino/c mice and exposed to LPS. Astrocytes from both brain areas already differed in their capacity and profile of cytokine expression under basal unstimulated conditions. In response to LPS, we observed both a region-specific pattern of up-regulation of distinct cytokines and differences in the extent and time-course of activation. Our data demonstrate that astrocytes reveal a region-specific basal profile of cytokine expression and a selective area-specific regulation of cytokines upon LPS-induced inflammation. This makes astrocytes likely candidates to be responsible for region-specific incidence rates of neurological and neurodegenerative disorders.

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Abbreviations

AD:

Alzheimer’s disease

ALS:

amyotrophic lateral sclerosis

as:

antisense

bFGF:

basic fibroblast growth factor

CD-40:

cluster of designation-40

CNS:

central nervous system

DNA:

deoxyribonucleic acid

EDTA:

ethylenediaminetetraacetic acid

GFAP:

glial cell line-derived neurotrophic factor

HPRT:

hypoxanthin-guanin-phosphoribosyl-transferase

IFN:

interferon

IL:

interleukin

LPS:

lipopolysaccharides

MCP-1:

monocyte chemo-attractant protein-1

M-CSF:

macrophage colony stimulating factor

MD-2:

myeloid differentiation protein-2

MIP-3α:

macrophage inflammatory protein-3α

MS:

multiple sclerosis

Myd88:

myeloid differentiation factor-88

OD:

optical density

PD:

Parkinson’s disease

PCR:

polymerase chain reaction

PGE2 :

prostaglandin E2

POS:

positive control

Neg:

negative control

RANTES:

regulated on activation, normal T-cell expressed and presumably secreted

RNA:

ribonucleic acid

RT:

reverse transcription

SDS:

sodiumdodecyl sulfate

s:

sense

TLR:

Toll-like receptor

TNFα:

tumor necrosis factor α

VEGF:

vascular epithelial growth factor

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Acknowledgment

This work was supported by a START grant from the Medical Faculty of the RWTH Aachen (M.K.). We would like to thank U. Zahn and H. Helten for their excellent technical support.

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Authors and Affiliations

  1. Institute of Neuroanatomy, Medical Clinic, RWTH Aachen, Wendlingweg 2, 52057, Aachen, Germany

    Markus Kipp, Akvile Norkute, Sonja Johann, Leila Lorenz, Alena Braun, Andrea Hieble, Stefan Gingele, Friederike Pott, Janek Richter & Cordian Beyer

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  1. Markus Kipp
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  2. Akvile Norkute
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  4. Leila Lorenz
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  10. Cordian Beyer
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Correspondence to Cordian Beyer.

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Kipp, M., Norkute, A., Johann, S. et al. Brain-Region-Specific Astroglial Responses In Vitro After LPS Exposure. J Mol Neurosci 35, 235–243 (2008). https://doi.org/10.1007/s12031-008-9057-7

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  • DOI: https://doi.org/10.1007/s12031-008-9057-7

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