Oleuropein aglycone and polyphenols from olive mill waste water ameliorate cognitive deficits and neuropathology

Abstract

Aim: In TgCRND8 (Tg) mice we checked the dose–response effect of diet supplementation with oleuropein aglycone (OLE) at 12.5 or 0.5 mg kg−1of diet. We also studied the effects of dietary intake of the mix of polyphenols present in olive mill waste water administered at a total dose as high as the highest dose of OLE (50 mg kg−1of diet) previously investigated. Methods: Four month-old Tg mice were equally divided into four groups and treated for 8 weeks with a modified low fat (5.0%) AIN-76 A diet (10 g day−1 per mouse) as such, supplemented with OLE (12.5 or 0.5 mg kg−1of diet) or with a mix of polyphenols (50 mg kg−1of diet) found in olive mill waste water. Behavioural performance was evaluated by the step down inhibitory avoidance and object recognition tests. Neuropathology was analyzed by immunohistochemistry. Results: OLE supplementation at 12.5 mg kg−1of diet and the mix of polyphenols was found to improve significantly cognitive functions of Tg mice (P < 0.0001). Aß42 and pE-3Aß plaque area and number were significantly reduced in the cortex by OLE and in the cortex and hippocampus by the mix of polyphenols (P < 0.01, P < 0.001 and P < 0.0001). Similar autophagy induction was found in the brain cortex of differently treated mice. Conclusion: Our results extend previous data showing that the effects of OLE on behavioural performance and neuropathology are dose-dependent and not closely related to OLE by itself. In fact, diet supplementation with the same dose of a mix of polyphenols found in olive mill waste water resulted in comparable neuroprotection.