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. J. Cell. Biochem. 112: 1450–1457, 2011. © 2011 Wiley‐Liss, Inc.