NR AXMK
AU Formentin,E.A.M.; Servida,F.; De Luigi,A.; Puricelli,M.; Ponti,W.; Poli,G.
TI Evaluation of Neuroinflammation Mechanisms in Co-cultures of Neurons, Astrocytes and Microglia from Newborn Hamsters
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.37
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB Inflammatory events mediated by activation of microglia and astrocytes partecipate to the neuronal death occuring in TSE. Cell activation is accompanied by morphological changes, proliferation and release of neurotoxic mediators. Understanding microgliaastrocyte interactions and the mechanisms involved in the regulation of microglia activation and neurotoxicity are important steps toward the identification of treatments for neurodegenerative diseases. The hamster model is commonly used for in vivo studies of TSE pathogenesis, but these studies lack of direct evidence of the functional properties exerted by activated microglia. We developed an astrocyte-microglia coculture system from neonatal hamster brains to study the molecular events related to glial activation. Moreover, we studied microglial induced apoptosis on hamster neurons in two different co-culture systems: microglia plated over neurons and microglia plated over a membrane well insert in the culture chamber of neurons, allowing medium exchange without physical contact of the two cell types. Astrocytemicroglia and neuron-microglia co-cultures were exposed to the neurotoxic, fibrillogenic HuPrP 106-126 peptide, using LPS and H2O2 as positive control and scrambled HuPrP 106-126 as negative control of glial activation. The presence of microglia in both the culture systems is necessary to stimulate, immediately after peptide inoculation, the production of mediators of oxidative stress (NO, ROS) and the mRNA expression of pro-inflammatory cytokines (IL-1beta and TNF-alfa by real-time RT PCR). These neurotoxic molecules are responsible for neuronal death even in the absence of a physical contact between neurons and microglia. Conversely to the rapid and high onset of IL-1beta and TNF-alfa, IL-10 expression is very low. IL-10 is a potent inhibitory factor in the CNS cytokine network involved in decreasing the expression of cytokine receptors as well as pro-inflammatory cytokine production by microglia.
AD E.A.M. Formentin, F. Servida, M. Puricelli, W. Ponti, G. Poli, Facoltà di Medicina Veterinaria, DIPAV, Italy; A. De Luigi, Mario Negri Institute for Pharmacological Research, Department of Neuroscience, Italy
SP englisch
PO Schottland
EA pdf-Datei und Poster (Postertitel: In vitro mechanisms of neuroinflammation in neuronal and astroglial co-culture systems from newborn hamsters)