Malliou, F.; Andriopoulou, C.E.; Kofinas, A.; Katsogridaki, A.; Leondaritis, G.; Gonzalez, F.J.; Michaelidis, T.M.; Darsinou, M.; Skaltsounis, L.A.; Konstandi, M. Oleuropein Promotes Neural Plasticity and Neuroprotection via PPARα-Dependent and Independent Pathways. Biomedicines2023, 11, 2250.
Malliou, F.; Andriopoulou, C.E.; Kofinas, A.; Katsogridaki, A.; Leondaritis, G.; Gonzalez, F.J.; Michaelidis, T.M.; Darsinou, M.; Skaltsounis, L.A.; Konstandi, M. Oleuropein Promotes Neural Plasticity and Neuroprotection via PPARα-Dependent and Independent Pathways. Biomedicines 2023, 11, 2250.
Malliou, F.; Andriopoulou, C.E.; Kofinas, A.; Katsogridaki, A.; Leondaritis, G.; Gonzalez, F.J.; Michaelidis, T.M.; Darsinou, M.; Skaltsounis, L.A.; Konstandi, M. Oleuropein Promotes Neural Plasticity and Neuroprotection via PPARα-Dependent and Independent Pathways. Biomedicines2023, 11, 2250.
Malliou, F.; Andriopoulou, C.E.; Kofinas, A.; Katsogridaki, A.; Leondaritis, G.; Gonzalez, F.J.; Michaelidis, T.M.; Darsinou, M.; Skaltsounis, L.A.; Konstandi, M. Oleuropein Promotes Neural Plasticity and Neuroprotection via PPARα-Dependent and Independent Pathways. Biomedicines 2023, 11, 2250.
Abstract
Oleuropein (OLE), a main constituent of olive, displays a pleiotropic beneficial dynamic in health and disease, based mainly on its antioxidant and hypolipidemic properties, and its capacity to protect myocardium during ischemia. Furthermore, OLE activates peroxisome proliferator-activated receptor (PPARα) in neurons and astrocytes, providing neuroprotection against noxious biological reactions that are induced following cerebral ischemia. Current study investigated the effect of OLE in the regulation of various neural plasticity indices, emphasizing the role of PPARα. For this purpose, 129/Sv wild-type (WT) and Pparα-null mice were treated with OLE for three weeks. The present findings revealed that chronic treatment with OLE up-regulated the brain-derived neurotrophic factor (BDNF) and its receptor TrkB in the prefrontal cortex (PFC) of mice via activation of ERK1/2, AKT and PKA/CREB signaling pathways. No similar effects were observed in the hippocampus. The OLE-induced effects on BDNF and TrkB appear to be mediated by PPARα, because no similar alterations were observed in the PFC of Pparα-null mice. Notably, OLE did not affect the neurotrophic factors NT3 and NT4/5 in both brain tissues. Fenofibrate though, a selective PPARα agonist, up-regulated BDNF and NT3 in the PFC of mice, whereas the drug induced NT4/5 in both brain sites tested. Interestingly, OLE provided neuroprotection in differentiated human SH-SY5Y cells against β-amyloid and H2O2 toxicity independently from PPARα activation. In conclusion, OLE and similar drugs acting either as PPARα agonists or via PPARα independent mechanisms could improve synaptic function/plasticity mainly in the PFC and to a lesser extent in the hippocampus, thus beneficially affecting cognitive functions.
Medicine and Pharmacology, Pharmacology and Toxicology
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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