Oleuropein Promotes Neural Plasticity and Neuroprotection via PPARα-Dependent and Independent Pathways

Oleuropein (OLE), a main constituent of olives, displays pleiotropic beneficial dynamic in health and disease; the effects are based mainly on its antioxidant hypolipidemic properties, capacity to protect myocardium during ischemia. Furthermore, OLE activates peroxisome proliferator-activated receptor (PPARα) neurons astrocytes, providing neuroprotection against noxious biological reactions that induced following cerebral The current study investigated effect regulation various neural plasticity indices, emphasizing role PPARα. For this purpose, 129/Sv wild-type (WT) Pparα-null mice were treated with for three weeks. findings revealed chronic treatment up-regulated brain-derived neurotrophic factor (BDNF) TrkB prefrontal cortex (PFC) via activation ERK1/2, AKT PKA/CREB signaling pathways. No similar observed hippocampus. OLE-induced BDNF appear be mediated by PPARα, because no alterations PFC mice. Notably, did not affect factors NT3 NT4/5 both brain tissues. However, fenofibrate, selective PPARα agonist, mice, whereas drug sites tested. Interestingly, provided differentiated human SH-SY5Y cells β-amyloid H2O2 toxicity independently from activation. In conclusion, drugs, acting either as agonists or independent mechanisms, could improve synaptic function/plasticity lesser extent hippocampus, thus beneficially affecting cognitive functions.