Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review
Longitudinal monoaminergic PET imaging of chronic proteasome inhibition in minipigs. / Lillethorup, Thea Pinholt; GLUD, AN; Alstrup, Aage Kristian Olsen et al.
In: Scientific Reports, Vol. 8, 15715, 24.10.2018.Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review
}
TY - JOUR
T1 - Longitudinal monoaminergic PET imaging of chronic proteasome inhibition in minipigs
AU - Lillethorup, Thea Pinholt
AU - GLUD, AN
AU - Alstrup, Aage Kristian Olsen
AU - Noer, Ove
AU - Nielsen, Erik Holm Toustrup
AU - Schacht, Anna Christina
AU - Landeck, Natalie
AU - Kirik, Deniz
AU - Orlowski, Dariusz
AU - Sørensen, Jens Christian Hedemann
AU - Doudet, Doris J
AU - Landau, Anne
PY - 2018/10/24
Y1 - 2018/10/24
N2 - Impairment of the ubiquitin proteasome system has been implicated in Parkinson’s disease. We used positron emission tomography to investigate longitudinal effects of chronic intracerebroventricular exposure to the proteasome inhibitor lactacystin on monoaminergic projections and neuroinflammation. Göttingen minipigs were implanted in the cisterna magna with a catheter connected to a subcutaneous injection port. Minipigs were imaged at baseline and after cumulative doses of 200 and 400 μg lactacystin, respectively. Main radioligands included [11C]-DTBZ (vesicular monoamine transporter type 2) and [11C]-yohimbine (α2-adrenoceptor). [11C]-DASB (serotonin transporter) and [11C]-PK11195 (activated microglia) became available later in the study and we present their results in a smaller subset of animals for information purposes only. Striatal [11C]-DTBZ binding potentials decreased significantly by 16% after 200 μg compared to baseline, but the decrease was not sustained after 400 μg (n = 6). [11C]-yohimbine volume of distribution increased by 18–25% in the pons, grey matter and the thalamus after 200 μg, which persisted at 400 μg (n = 6). In the later subset of minipigs, we observed decreased [11C]-DASB (n = 5) and increased [11C]-PK11195 (n = 3) uptake after 200 μg. These changes may mimic monoaminergic changes and compensatory responses in early Parkinson’s disease.
AB - Impairment of the ubiquitin proteasome system has been implicated in Parkinson’s disease. We used positron emission tomography to investigate longitudinal effects of chronic intracerebroventricular exposure to the proteasome inhibitor lactacystin on monoaminergic projections and neuroinflammation. Göttingen minipigs were implanted in the cisterna magna with a catheter connected to a subcutaneous injection port. Minipigs were imaged at baseline and after cumulative doses of 200 and 400 μg lactacystin, respectively. Main radioligands included [11C]-DTBZ (vesicular monoamine transporter type 2) and [11C]-yohimbine (α2-adrenoceptor). [11C]-DASB (serotonin transporter) and [11C]-PK11195 (activated microglia) became available later in the study and we present their results in a smaller subset of animals for information purposes only. Striatal [11C]-DTBZ binding potentials decreased significantly by 16% after 200 μg compared to baseline, but the decrease was not sustained after 400 μg (n = 6). [11C]-yohimbine volume of distribution increased by 18–25% in the pons, grey matter and the thalamus after 200 μg, which persisted at 400 μg (n = 6). In the later subset of minipigs, we observed decreased [11C]-DASB (n = 5) and increased [11C]-PK11195 (n = 3) uptake after 200 μg. These changes may mimic monoaminergic changes and compensatory responses in early Parkinson’s disease.
UR - https://rdcu.be/9XQ9
U2 - 10.1038/s41598-018-34084-5
DO - 10.1038/s41598-018-34084-5
M3 - Journal article
C2 - 30356172
VL - 8
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 15715
ER -