RAGE and S100B: Partners in neuroprotection?.

RAMOS AJ, ACCORINTI J, BRUSCO A

Magdeburg, Alemania

Congreso; 4th International Symposium on Neuroprotection and Neurorepair,; 2006

  RAGE AND S100B: PARTNERS IN NEUROPROTECTION?   Ramos AJ*, Accorinti J, Brusco A Instituto de Biología Celular y Neurociencias “Prof. E. De Robertis”, Facultad de Medicina, Universidad de Buenos Aires, Argentina. E-mail: ajramos@mail.retina.ar We previously demonstrated that 5HT1A receptor agonists induce neuroprotection in a model of cortical devascularization (CD) (Ramos et al., Brain Res, 1030: 201-220, 2004) and the neuroprotection correlates with the increased S100B level in the extracellular space. S100B is a trophic factor that presents pro-survival activity in neuronal cultures when it is in the nanomolar concentration level and its effects seems to be mediated by the Receptor for Advanced Glycosylation End Products (RAGE). Using the cortical devascularization model (CD; unilateral pial disruption), we analyzed the profile of RAGE expression as well as its cellular localization. Wistar rats were subjected to CD lesion which consisted of a craniotomy followed by physical damage to the underlying pial blood vessels. To induce excitotoxicity in vitro, rat cortical primary neurons of 6DIV were exposed to glutamate during 5 min, washed and analyzed 24hs later. Primary neurons exposed to glutamate and brain sections of animals sacrificed at 3, 7 or 14 days post-lesion, were processed for western blot or immunohistochemistry to detect RAGE, S100B and glial (GFAP, vimentin) or neuronal markers (neurofilaments, MAP-2). Images were analyzed and quantified by digital image analysis. Our results showed that injury induces RAGE expression both in neurons and astroglial cells after CD in vivo and primary neurons presented robust RAGE expression after excitotoxicity. These results demonstrate that RAGE is present in the area of the CD injury and that released S100B could interact with its receptor to induce the prosurvival effects. Since RAGE is also able to mediate the S100B deleterious effects (over the micromolar range of concentration)  the equilibrium between these prosurvival/prodeath effects seems to depend on the S100B concentration reached in the extracellular space. Supported by grants of CONICET PIP 6063 (AJR); TWAS (AJR) and UBACYT (AB).