TY - JOUR A1 - Gonzalo-Ruiz, Alicia A1 - Delso, Maria A1 - Carrero, Isabel A1 - Gonzalo Vicente, Pilar A1 - Sanz-Anquela, José Miguel A1 - Rodríguez, Manuel A1 - Arévalo-Serrano, Juan T1 - A rat model of oligomeric forms of beta-amyloid (A?) peptide: neuronal loss, synaptic alteration, astrogliosis, and calcium-binding proteins activation in vivo JO - Eur. J. Anat. SN - 1136-4890 Y1 - 2011 VL - 15 SP - 47 EP - 72 UR - http://www.eurjanat.com/web/paper.php?id=110005ag KW - Alzheimer??s disease KW - Retrosplenial cortex KW - Astrocytosis KW - S100B KW - Calpain-1 N2 - Oligomers of Beta-amyloid (A?) peptide are presumed to cause synaptic and cognitive dysfunction in Alzheimer??s disease (AD). However, their contribution to other pathological features of AD remains unclear. To address the latter, we applied microinjections of A?1-42 oligomers into the retrosplenial cortex of the rat. We observed that A?1-42 induced a greater reduction in neuronal density as compared with that seen at control (A?42-1) injections. Oligomers of A?1-42 peptide caused synaptic alterations, as evidenced by the decrease in the presynaptic marker synaptophysin and the increase in chromogranin A. We also detected a marked interaction between GFAP-, and A?immunoreactive material in a time-dependent manner. To address the possible mechanisms involved in astrocyte activation, we analyzed the interaction between the calcium-dependent protease, calpain-1, and the calcium-binding protein, S100B, and astrogliosis in response to A? toxicity. Calpain-1 activation was studied by immunoblotting. Three immunopositive protein bands (80kDa, 76kDa, and 18kDa) were detected. Densitometry analyses revealed a significant increase in calpain-1 at 76kDa and at position 18kDa in A?1-42-treated animals as compared with the corresponding bands in control animals. Confocal analysis showed codistribution of A?-, and calpain 1-immunoreactivities in cortical cells, and in reactive astrocytes surrounding the injection of A?, and both cortical and leptomeningeal blood vessels. A colocalization of GFAP and S100B proteins was observed in astrocytes that surrounded the A? injection, and also in reactive astrocytes in close association with blood vessels. In conclusion, our results suggest that calpain-1 and S100B might play a critical role in astroglisois in response to A? toxicity. ER -