Journal article
Glia maturation factor modulates β-amyloid-induced glial activation, inflammatory cytokine/chemokine production and neuronal damage
Brain research, Vol.1208, pp.192-203
05/07/2008
DOI: 10.1016/j.brainres.2008.02.093
PMCID: PMC2587299
PMID: 18395194
Abstract
Abstract Glia maturation factor (GMF), discovered and characterized in our laboratory, is a highly conserved protein primarily localized in mammalian central nervous system. Previously we demonstrated that GMF is required in the induced production of proinflammatory cytokines and chemokines in brain cells. We now report that ventricular infusion of human amyloid beta peptide1-42 (Aβ1-42) in mouse brain caused glial activation and large increases in the levels of GMF as well as induction of inflammatory cytokine/chemokine known for launching the neuro inflammatory cascade in Alzheimer's disease (AD). To test the hypothesis that GMF is involved in the pathogenesis of AD, we infused Aβ1-42 in the brain of GMF-deficient (GMF-KO) mice, recently prepared in our laboratory. GMF-deficient mice showed reduced glial activation and significantly suppressed proinflammatory cytokine/chemokine production following Aβ infusion compared to wild type (Wt) mice. The decrease in glial activation in the GMF-KO mice is also associated with significant reduction in Aβ induced loss of pre-synaptic marker, synaptophysin, and post-synaptic density protein-95 (PSD 95). We also examined the potential relationship between GMF or lack of it with learning and memory using the T-maze, Y-maze, and water maze, hippocampal-dependent spatial memory tasks. Our results show that memory retention was improved in GMF-KO mice compared to Wt controls following Aβ infusion. Diminution of these Aβ1-42 effects in primary cultures of GMF-KO astrocyte and microglia were reversed by reconstituted expression of GMF. Taken together, our results indicate a novel mediatory role of GMF in the neuro-inflammatory pathway of Aβ and its pro-inflammatory functions.
Details
- Title: Subtitle
- Glia maturation factor modulates β-amyloid-induced glial activation, inflammatory cytokine/chemokine production and neuronal damage
- Creators
- Asgar ZaheerSmita ZaheerRamasamy ThangavelYanghong WuShailendra K. SahuBaoli Yang - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Brain research, Vol.1208, pp.192-203
- DOI
- 10.1016/j.brainres.2008.02.093
- PMID
- 18395194
- PMCID
- PMC2587299
- NLM abbreviation
- Brain Res
- ISSN
- 0006-8993
- eISSN
- 1872-6240
- Publisher
- Elsevier B.V
- Language
- English
- Date published
- 05/07/2008
- Academic Unit
- Neurology; Obstetrics and Gynecology
- Record Identifier
- 9983557777102771
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