0000000000441255

AUTHOR

Raul Herance

[11C]-DASB microPET imaging in the aged rat: Frontal and meso-thalamic increases in serotonin transporter binding

Whereas molecular imaging studies in the aging human brain have predominantly demonstrated reductions in serotonin transporter (5-HTT) availability, the majority of the rodent studies, using autoradiographic methods, report increases in neural 5-HTT levels with age. To our knowledge, however, no previous rodent studies have assessed this topic in vivo, and therefore it remains unclear whether this discrepancy arises from methodological or inter-species differences. We performed an [(11)C]-DASB microPET study to evaluate the effects of aging on 5-HTT availability in the rat brain. To generate binding potential estimates, quantitative tracer kinetic modeling was applied using the simplified r…

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THE EFFECTS OF AGING ON DOPAMINERGIC NEUROTRANSMISSION A microPET STUDY OF [11C]-raclopride BINDING IN THE AGED RODENT BRAIN

Rodent models are frequently used in aging re search to investigate biochemical age effects and aid in the development of therapies for pathological and non pathological age related degenerative processes In order to validate the use of animal models in aging research and pave the way for longitudinal intervention based animal studies, the consistency of cerebral aging processes across species needs to be evaluated The dopaminergic system seems particularly susceptible to the aging process, and one of the most consistent findings in human brain aging research is a decline in striatal D2-like receptor (D2R) availability, quantifiable by positron emission tomography (PET) imaging In this stud…

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In vivo molecular imaging of the GABA/benzodiazepine receptor complex in the aged rat brain

The GABA-ergic system, known to regulate neural tissue genesis during cortical development, has been postulated to play a role in cerebral aging processes. Using in vivo molecular imaging and voxel-wise quantification, we aimed to assess the effects of aging on the benzodiazepine (BDZ) recognition site of the GABA A receptor. To visualize BDZ site availability, [C-11]-flumazenil microPET acquisitions were conducted in young and old rats. The data were analyzed and region of interest analyses were applied to validate the voxel-wise approach. We observed decreased [C-11]-flumazenil binding in the aged rat brains in comparison with the young control group. More specifically, clusters of reduce…

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Evidence for a relationship between mitochondrial Complex I activity and mitochondrial aldehyde dehydrogenase during nitroglycerin tolerance: effects of mitochondrial antioxidants.

The medical use of nitroglycerin (GTN) is limited by patient tolerance. The present study evaluated the role of mitochondrial Complex I in GIN biotransformation and the therapeutic effect of mitochondrial antioxidants. The development of GIN tolerance (in rat and human vessels) produced a decrease in mitochondrial 02 consumption. Co-incubation with the mitochondria-targeted antioxidant mitoquinone (MQ 10(-6) mol/L) or with glutathione ester (GEE, 10(-4) mol/L) blocked GTN tolerance and the effects of GTN on mitochondrial respiration and aldehyde dehydrogenase 2 (ALDH-2) activity. Biotransformation of GTN depended on the mitochondria being functionally active, particularly mitochondrial Comp…

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