title: Effect of β-amyloid (25-35) on mitochondrial function and expression of mitochondrial permeability transition pore proteins in rat hippocampal neurons.
abstract: The aim of this study was to assess the effect of the β-amyloid fragment Aβ(25-35) on mitochondrial structure and function and on the expression of proteins associated with the mitochondrial permeability transition pore (MPTP) in rat hippocampal neurons. Ninety clean-grade Sprague-Dawley rats were randomly assigned to six groups (n = 15 per group). Aβ(25-35) (1, 5, or 10 µg/rat) was injected into hippocampal area CA1. Normal saline was injected as a control. The effect of Aβ(25-35) injection on hippocampal structure was assessed by transmission electron microscopy. Ca(2+) -ATPase activity, [Ca(2+) ](i) , and mitochondrial membrane potential were measured. The expression of genes associated with the MPTP, including the voltage-dependent anion channel (VDAC), adenine nucleotide translocator (ANT), and cyclophilin D (Cyp-D), were evaluated. Results showed that Aβ(25-35) injection damaged the mitochondrial structure of hippocampal neurons, decreased Ca(2+) -ATPase activity and mitochondrial membrane potential, and increased [Ca(2+) ](i) . The expression levels for VDAC, ANT, and Cyp-D in all groups were significantly (P < 0.05) higher than those in the normal control group after Aβ(25-35) injection. These results indicate that Aβ(25-35) damages mitochondria in rat hippocampal neurons and effects mitochondrial dysfunction, as well as increasing the expression of genes associated with the MPTP. Mitochondrial dysfunction may result in increased MPTP gene expression, leading to neurodegenerative effects.
authors.affiliation: Toxicology Group, Public Health College, Harbin Medical University, Harbin, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Ren
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Benchang
authors.initials: B
authors.lastname: Li
authors.forename: Yanping
authors.initials: Y
authors.lastname: Wu
authors.forename: Baixiang
authors.initials: B
authors.lastname: Li
mesh_terms: D033741:Adenine Nucleotide Translocator 1 / Q000032:analysis; D016229:Amyloid beta-Peptides / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000032:analysis; D005260:Female; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics*; D000083162:Mitochondrial Permeability Transition Pore; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050994:Voltage-Dependent Anion Channels / Q000235:genetics
chemical_list: D033741:Adenine Nucleotide Translocator 1; D016229:Amyloid beta-Peptides; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D010446:Peptide Fragments; D050994:Voltage-Dependent Anion Channels; C074636:amyloid beta-protein (25-35); D002118:Calcium