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Area 4: Molecular recognition in biomolecules
Molecular and functional approaches to investigate the
neuroprotective and neuromodulatory roles of chemokines and their
receptors in the central nervous system.
Cristina Limatola
Department of Physiology and Pharmacology "Vittorio Erspamer"
: +39 06 49690243 - @: [email protected]
Proposal summary
In the last few years, we demonstrated that CX3CL1 protects hippocampal neurons from glutamateinduced excitotoxicity and that this protective mechanism requires the presence of extracellular adenosine,
acting through adenosine receptor 1 (A1R, Limatola, 2005; Lauro, 2008, 2010). More recently we also
demonstrated that CX3CL1 is neuroprotective in an in vivo model of cerebral ischemia in mice and rats and
that CX3CL1 activity again requires the presence of A1R, being its protective effects absent in A1R-/- mice
or in the presence of the A1R antagonist DPCPX (Cipriani et al., 2011). Recently, we also demonstrated for
the first time that CXCL16 has neuroprotective roles in the nervous system, reducing Glu-induced
excitotoxicity, in hippocampal cultures, with mechanisms requiring A3R and astrocyte-derived CCL2 (Rosito
et al., 2012).
In the present project we plan to further develop these studies investigating the effects of CX3CL1 and
CXCL16 on glial cells (astrocytes and microglia) focusing our attention on 1) Glu transporter activity,
expression and localization, 2) glutamine synthase expression, 3) microRNA (miRNA) modulation, 4) release
of soluble factors. Similarly to what performed on CX3CL1, we also want to investigate the protective
effects of CXCL16 in in vivo models of cerebral ischemia and its potential neuromodulatory action on
glutamatergic and GABAergic synaptic transmission, on synaptic plasticity, and the potential role of the
transmembrane chemokines CX3CL1 and CXCL16 in functional rescue of synaptic transmission upon
ischemic conditions.
GROUP COMPONENTS
Francesca GRASSI, professor; Davide RAGOZZINO, professor; Eleonora PALMA, professor; Sergio FUCILE,
professor; Flavia TRETTEL, researcher; Myriam CATALANO, researcher; Laura MAGGI, researcher;
Massimiliano RENZI researcher; Clotilde LAURO, technician; Giuseppina D’ALESSANDRO, postDoc fellow;
Maria ROSITO, postDoc fellow; Alfonso GRIMALDI phD student; Stefano GAROFALO phD student;
Giuseppina CHECE, technician; Fabrizio CICCHITTO technician.

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