Enhanced expression of glia maturation factor correlates with glial activation in the brain of triple transgenic Alzheimer's disease mice.

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.

• Authors: Smita Zaheer, Ramasamy Thangavel, Yanghong Wu, Mohammad Moshahid Khan, Duraisamy Kempuraj, Asgar Zaheer
• Journal: Neurochemical research (Neurochem Res) Vol. 38 Issue 1 Pg. 218-25 (Jan 2013) ISSN: 1573-6903 [Electronic] United States
• PMID: 23086473 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Amyloid beta-Protein Precursor
• Chemokines
• Cytokines
• Glia Maturation Factor
• Presenilin-1
• tau Proteins

Topics

• Alzheimer Disease (genetics, metabolism, psychology)
• Amyloid beta-Protein Precursor (genetics)
• Animals
• Blotting, Western
• Brain (immunology)
• Brain Diseases (genetics, pathology)
• Chemokines (biosynthesis)
• Cognition Disorders (genetics, psychology)
• Cytokines (biosynthesis)
• Enzyme-Linked Immunosorbent Assay
• Fluorescent Antibody Technique
• Glia Maturation Factor (biosynthesis)
• Humans
• Immunohistochemistry
• Long-Term Potentiation (genetics, physiology)
• Macrophage Activation (genetics)
• Mice
• Mice, Transgenic
• Neurofibrillary Tangles (genetics, pathology)
• Neuroglia (immunology, physiology)
• Neuronal Plasticity (genetics, physiology)
• Plaque, Amyloid (genetics, pathology)
• Presenilin-1 (genetics)
• Real-Time Polymerase Chain Reaction
• tau Proteins (genetics)