Abstract
We previously demonstrated that glia maturation factor (GMF), a brain specific protein, isolated, sequenced and cloned in our laboratory, induce expression of proinflammatory cytokines and chemokines in the central nervous system. We also reported that the up-regulation of GMF in astrocytes leads to the destruction of neurons suggesting a novel pathway of GMF-mediated cytotoxicity of brain cells, and implicated its involvement in the pathogenesis of inflammatory neurodegenerative diseases. In the present study, we examined the expressions of GMF in triple-transgenic Alzheimer’s disease (3xTg-AD) mice. Our results show a 13-fold up-regulation of GMF and 8–12-fold up-regulation of proinflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), IL-1β, interferon gamma (IFN-γ), and chemokine (C–C motif) ligand 2 (CCL2) and C–X–C motif chemokine 10 (CXCL10/IP-10) mRNA as determined by quantitative real-time RT-PCR in the brain of 3xTg-AD mice as compared to non-transgenic (Non-Tg) mice. In conclusion, the increase in GMF and cytokine/chemokine expression was correlated with reactive glial fibrillary acidic protein positive astrocytes and ionized calcium binding adaptor molecule 1 (Iba-1)-positive microglia in 3xTg-AD mice.
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Abbreviations
- CCL2:
-
Chemokine (C–C motif) ligand 2
- CXCL10:
-
C–X–C motif chemokine 10
- CNS:
-
Central nervous system
- ELISA:
-
Enzyme-linked immunosorbent assay
- GFAP:
-
Glial fibriallary acidic protein
- IFN-γ:
-
Interferon-gamma
- IL-1:
-
Interleukin-1
- Non-Tg:
-
Non-transgenic mice
- GMF:
-
Glia maturation factor
- Real-time PCR:
-
Real-time polymerase chain reaction
- 3xTg-AD mice:
-
Triple transgenic Alzheimer’s disease
- TNF-α:
-
Tumor necrosis factor-alpha
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Acknowledgments
We thank Scott Knight, Ashna Zaheer, and Marcus Ahrens for excellent technical help. 3xTg-AD mice were from Dr. Frank M. LaFerla, University of California, Irvine, obtained from Dr. Gloria Lee, University of Iowa. This work was supported by the Department of Veterans Affairs Merit Review award (to A.Z.) and by the National Institute of Neurological Disorders and Stroke grant NS-47145 (to A.Z.).
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Zaheer, S., Thangavel, R., Wu, Y. et al. Enhanced Expression of Glia Maturation Factor Correlates with Glial Activation in the Brain of Triple Transgenic Alzheimer’s Disease Mice. Neurochem Res 38, 218–225 (2013). https://doi.org/10.1007/s11064-012-0913-z
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DOI: https://doi.org/10.1007/s11064-012-0913-z