title: Monitoring of neuronal loss in the hippocampus of Aβ-injected rat: autophagy, mitophagy, and mitochondrial biogenesis stand against apoptosis.
abstract: In the present study, we tried to answer the following questions: which kind of defense pathways are activated after Aβ insult? How defense systems react against noxious effects of Aβ and whether they are able to deal against apoptosis or not? So, we traced some molecular pathways including autophagy, mitophagy, and mitochondrial biogenesis before reaching to the endpoint of apoptosis. Besides, we measured the function of mitochondria after injection of Aβ (1-42) in CA1 area of hippocampus as a model of Alzheimer's disease (AD). Based on our data, autophagy markers reached to their maximum level and returned to the control level as apoptotic markers started to increase. As a specialized form of autophagy, mitophagy markers followed the trend of autophagy markers. Whereas mitochondrial dynamic processes shifted toward fission, mitochondrial biogenesis was severely affected by Aβ and significantly decreased. Alongside suppression of mitochondrial biogenesis, activity of specific enzymes involved in antioxidant defense system, electron transport chain, and tricarboxylic acid cycle (TCA) decreased in response to the Aβ. Activity of antioxidant enzymes increased at first and then decreased significantly compared to the control. TCA enzymes aconitase and malate dehydrogenase activities reduced immediately while citrate synthase and fumarase activities did not change. Based on our finding, monitoring of the master molecules of intracellular cascades and determining their trends before the destructive function of Aβ could be the target of therapeutic issues for AD.
authors.affiliation: NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Shaerzadeh
authors.forename: Fereshteh
authors.initials: F
authors.lastname: Motamedi
authors.forename: Dariush
authors.initials: D
authors.lastname: Minai-Tehrani
authors.forename: Fariba
authors.initials: F
authors.lastname: Khodagholi
mesh_terms: D000154:Aconitate Hydratase / Q000032:analysis; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000473:pathology; D002374:Catalase / Q000032:analysis; D002950:Citrate (si)-Synthase / Q000032:analysis; D002952:Citric Acid Cycle / Q000187:drug effects*; D003580:Cytochromes / Q000032:analysis; D004579:Electron Transport; D004790:Enzyme Induction; D005649:Fumarate Hydratase / Q000032:analysis; D005978:Glutathione / Q000032:analysis; D008291:Malate Dehydrogenase / Q000032:analysis; D008297:Male; D008845:Microinjections; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D063306:Mitophagy / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D010446:Peptide Fragments / Q000633:toxicity*; D011494:Protein Kinases / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000032:analysis; D013997:Time Factors; D000099202:PTEN-Induced Putative Kinase
chemical_list: D000154:Aconitate Hydratase; D016229:Amyloid beta-Peptides; D002374:Catalase; D002950:Citrate (si)-Synthase; D003580:Cytochromes; D005649:Fumarate Hydratase; D005978:Glutathione; D008291:Malate Dehydrogenase; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D011494:Protein Kinases; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D000099202:PTEN-Induced Putative Kinase; C075222:amyloid beta-protein (1-42)