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Effects of amyloid-β deposition on mitochondrial complex I | 48817

Journal of Neuroscience and Neuropharmacology

Effects of amyloid-β deposition on mitochondrial complex I activity in brain: A PET study in aged monkeys

4th Global Experts Meeting on Neuropharmacology

September 14-16, 2016 San Antonio, USA

Hideo Tsukada

Hamamatsu Photonics K.K., Japan

Scientific Tracks Abstracts: Neurochem Neuropharm

Abstract :

FDG-PET is a well-established technique for quantitative imaging of the regional cerebral metabolic rate of glucose (rCMRglc) in living brain. However, the unexpectedly high uptake of 18F-FDG in ischemia-damaged areas suggested that 18F-FDG was taken up into not only normal tissues but also inflammatory regions with microglial activation, which hampers the accurate diagnose of brain function. To solve this problem, the translational research with 18F-BCPP-EF, a novel PET probe for mitochondrial complex 1 (MC-1) activity was conducted using an animal PET to assess the aging effects on MC-I activity in monkey brain (Macaca mulatta). PET scans using 11C-PIB for A�², 11C-DPA-713 for inflammation (TSPO), 18F-FDG for rCMRglc, and 18F-BCPP-EF for MC-1 were performed under conscious states in young and aged animals. When plotted VT of 18F-BCPP-EF against SUVR of 11C-PIB in the cerebral cortical regions, it showed a significant negative correlation between them. Plotting of SUV of 11C-DPA-713 against SUVR of 11C-PIB resulted in a significant positive correlation, suggesting that A�² deposition-induced inflammatory effects with microglial activation. In contrast, plotting of rCMRglc against SUVR of 11C-PIB did not reach statistically significant level. Furthermore, we recently reported in TauTg mice the negative correlation between the uptake of 11C-PBB3, a PET probe for imaging Tau deposition, and MC-I in hippocampus, and positive correlation between memory function and MC-I activity measured using 18F-BCPP-EF. These results strongly suggested that 18F-BCPP-EF could discriminate the neuronal damaged areas with neuroinflammation, where 18F-FDG could not owing to its high uptake into the activated microglia.

Biography :

Hideo Tsukada received PhD from Shizuoka College of Pharmacy, Japan. He was a visiting researcher in Uppsala University PET Center, Directed by Professor Bengt Langstrom, from 1990 to 91. At present, he is the senior manager of PET Center, Central Research Laboratory, Hamamatsu Photonics, Japan, and conducting PET researches in preclinical to clinical stages. He has published more than 250 papers, being awarded by the Society for Nuclear Medicine (2009), and Japan Molecular Imaging Award (2010). He is serving as the visiting Professor in Hamamatsu University School of Medicine, and University of Shizuoka, School of Pharmaceutical Sciences.

Email: tsukada0412@nifty.com

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