Browsing by Author "Ordenes, Daniela"

Now showing 1 - 2 of 2
  • No Thumbnail Available
    Item
    Peroxisome Proliferator-Activated Receptor (PPAR) γ and PPARα Agonists Modulate Mitochondrial Fusion-Fission Dynamics: Relevance to Reactive Oxygen Species (ROS)-Related Neurodegenerative Disorders?
    (2013) Zolezzi, Juan M.; Silva-Alvarez, Carmen; Ordenes, Daniela; Godoy, Juan A.; Carvajal, Francisco J.; Santos, Manuel J.; Inestrosa, Nibaldo C.
    Recent studies showed that the activation of the retinoid X receptor, which dimerizes with peroxisome proliferator-activated receptors (PPARs), leads to an enhanced clearance of A beta from the brain of transgenic mice model of Alzheimer's disease (AD), because an increased expression of apolipoprotein E and it main transporters. However, the effects observed must involve additional underlying mechanisms that have not been yet explored. Several studies conducted in our laboratory suggest that part of the effects observed for the PPARs agonist might involves mitochondrial function and, particularly, mitochondrial dynamics. In the present study we assessed the effects of oxidative stress challenge on mitochondrial morphology and mitochondrial dynamics-related proteins in hippocampal neurons. Using immunofluorescence, we evaluated the PPAR gamma co-activator 1 alpha (PGC-1 alpha), dynamin related protein 1 (DRP1), mitochondrial fission protein 1 (FIS1), and mitochondrial length, in order to determine if PPARs agonist pre-treatment is able to protect mitochondrial population from hippocampal neurons through modulation of the mitochondrial fusion-fission events. Our results suggest that both a PPAR gamma agonist (ciglitazone) and a PPAR alpha agonist (WY 14.643) are able to protect neurons by modulating mitochondrial fusion and fission, leading to a better response of neurons to oxidative stress, suggesting that a PPAR based therapy could acts simultaneously in different cellular components. Additionally, our results suggest that PGC-1 alpha and mitochondrial dynamics should be further studied in future therapy research oriented to ameliorate neurodegenerative disorders, such as AD.
  • No Thumbnail Available
    Item
    Tetrahydrohyperforin Induces Mitochondrial Dynamics and Prevents Mitochondrial Ca2+ Overload after Aβ and Aβ-AChE Complex Challenge in Rat Hippocampal Neurons
    (2013) Zolezzi, Juan M.; Carvajal, Francisco J.; Rios, Juvenal A.; Ordenes, Daniela; Silva-Alvarez, C.; Godoy, Juan A.; Inestrosa, Nibaldo C.
    St. John's wort has been the subject of studies focused on its therapeutic properties against several diseases, including Alzheimer's disease (AD). Amyloid beta-peptide (A beta), a critical peptide in AD, has been linked to the mitochondrial dysfunction often observed in this disease. Despite many efforts to prevent A beta levels from increasing in AD, less has been done regarding the mitochondrial component. Therefore, we studied the effects of tetrahydrohyperforin (THH) on mitochondrial dysfunction of hippocampal neurons, challenged with A beta oligomers (A beta o) and A beta o-AChE complexes. We show that THH prevents mitochondrial calcium overload and induces the modulation of fusion-fission events, arresting mitochondrial dysfunction. Moreover, our results suggest that the modulation of mitochondrial dynamics probably occurs through a peroxisome proliferator-activated receptor gamma co-activator 1 alpha-mediated mechanism, inducing mitochondrial fusion-fission protein expression. Our results offer further explanation for the effects observed for THH and the beneficial effects of this ethno-botanical drug in AD.