Monitoring of Neuronal Loss in the Hippocampus of Aβ-Injected Rat: Autophagy, Mitophagy, and Mitochondrial Biogenesis Stand Against Apoptosis

• Published in: Neuromolecular medicine Vol. 16; no. 1; pp. 175 - 190
• Main Authors: Shaerzadeh, Fatemeh, Motamedi, Fereshteh, Minai-Tehrani, Dariush, Khodagholi, Fariba
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.03.2014
• Subjects: Aconitate hydratase; Aconitate Hydratase - analysis; Amyloid beta-Peptides - toxicity; Animals; Apoptosis - drug effects; Autophagy - drug effects; Biomedical and Life Sciences; Biomedicine; CA1 Region, Hippocampal - drug effects; CA1 Region, Hippocampal - pathology; Catalase - analysis; Citrate (si)-Synthase - analysis; Citric Acid Cycle - drug effects; Cytochromes - analysis; Electron Transport; Enzyme Induction; Fumarate Hydratase - analysis; Glutathione - analysis; Internal Medicine; Malate Dehydrogenase - analysis; Male; Microinjections; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondrial Degradation - drug effects; Nerve Tissue Proteins - analysis; Nerve Tissue Proteins - physiology; Neurology; Neurons - drug effects; Neurons - pathology; Neurosciences; Original Paper; Peptide Fragments - toxicity; Protein Kinases - analysis; Rats; Rats, Wistar; Reactive Oxygen Species - metabolism; Superoxide Dismutase - analysis; Time Factors; Amyloid beta; Mitochondrial biogenesis; Alzheimer’s disease; Autophagy; Apoptosis
• ISSN: 1535-1084; 1559-1174
• DOI: 10.1007/s12017-013-8272-8

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.