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Comparing α7 nicotinic acetylcholine receptor binding, amyloid‐β deposition, and mitochondria complex‐I function in living brain: A PET study in aged monkeys
Author(s) -
Nishiyama Shingo,
Ohba Hiroyuki,
Kanazawa Masakatsu,
Kakiuchi Takeharu,
Tsukada Hideo
Publication year - 2015
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.21842
Subject(s) - nicotinic agonist , acetylcholine receptor , neuroscience , mitochondrion , acetylcholine , nicotinic acetylcholine receptor , amyloid (mycology) , brain function , chemistry , pharmacology , receptor , microbiology and biotechnology , medicine , biology , biochemistry , pathology
This study was aimed to assess the correlations among α7 nicotinic acetylcholine receptor (α7‐nAChR) binding, amyloid‐β (Aβ) deposition, and mitochondrial complex I (MC‐I) activity in the brain of aged monkeys ( Macaca mulatta ). Positron emission tomography (PET) measurements with [ 11 C]( R )‐MeQAA, [ 11 C]PIB, and [ 18 F]BCPP‐EF were conducted in monkeys in a conscious condition. [ 11 C]( R )‐MeQAA binding was analyzed by a simplified reference tissue model to calculate nondisplaceable binding potential (BP ND ), [ 11 C]PIB uptake was calculated by standard uptake value ratio (SUVR), and [ 18 F]BCPP‐EF binding was determined by Logan graphical analysis to calculate total distribution volume ( V T ) with arterial blood sampling. Higher brain uptake was determined in the thalamus, hippocampus, striatum, and cortical regions for [ 11 C]( R )‐MeQAA, while being lower in the cerebellum. Significant age‐related reduction of [ 11 C]( R )‐MeQAA binding to α7‐nAChR was determined only in the occipital cortex. The plot of Vt of [ 18 F]BCPP‐EF against BP ND of [ 11 C]( R )‐MeQAA indicated a significant negative correlation in the hippocampus and cortical regions in aged animals. Plotting of SUVR of [ 11 C]PIB against BP ND of [ 11 C]( R )‐MeQAA showed a positive correlation. The in vivo binding of [ 11 C]( R )‐MeQAA could reflect the upregulation of α7‐nAChR induced by neurodegenerative damage determined by Aβ deposition as well as impaired MC‐I activity in living brain. Synapse 69:475–483, 2015. © 2015 Wiley Periodicals, Inc.