Oleuropein aglycone counteracts Aβ42 toxicity in the rat brain

Previous data have shown that oleuropein aglycone (OLE), the main secoiridoid phenol present in extra virgin olive oil, counteracts in vitro aggregation of the Aβ42 peptide and protects cultured cells and model organisms against aggregates toxicity. In this study we investigated the relative tissue toxicity of Aβ42 aggregated in vitro in the presence or in the absence of OLE by injecting the nucleus basalis magnocellularis (NBM) of adult male Wistar rats with a 1.5 μl solution containing OLE (450 μM) or Aβ42 (50 μM) aggregated in the absence (oligomers) or in the presence of 450 μM OLE. Control rats were injected with vehicle (1.5 μl). Thirty days after injection, the number of choline acetyltransferase (ChAT)-positive neurons, glia reaction and the Aβ peptide levels were detected by immunohistochemistry. An apparent reduction in the amount of soluble A11-positive oligomers was detected in the NBM injected with Aβ42 aggregated with OLE, as compared with the NBM injected with Aβ42 alone. In the latter case, the number of ChAT-positive neurons was significantly reduced (≈-33%) respect to that recorded in the NBM injected with phosphate buffer, OLE or Aβ42 aggregated with OLE. A markedly attenuated Aβ-induced astrocytes and microglia reaction was also found in the NBM injected with Aβ42 aggregated with OLE. Altogether, these data provide additional support to the anti-aggregation, neuroprotective and anti-inflammatory activities of this natural phenol, confirming its beneficial properties against neurodegeneration.