A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
[F-18]FMPEP-d(2) PET imaging shows age- and genotype-dependent impairments in the availability of cannabinoid receptor 1 in a mouse model of Alzheimer's disease
Tekijät: Jatta S. Takkinen, Francisco R. López-Picón, Anna K. Kirjavainen, Rea Pihlaja, Anniina Snellman, Tamiko Ishizu, Eliisa Löyttyniemi, Olof Solin, Juha O. Rinne, Merja Haaparanta-Solin
Kustantaja: ELSEVIER SCIENCE INC
Julkaisuvuosi: 2018
Journal: Neurobiology of Aging
Tietokannassa oleva lehden nimi: NEUROBIOLOGY OF AGING
Lehden akronyymi: NEUROBIOL AGING
Vuosikerta: 69
Aloitussivu: 199
Lopetussivu: 208
Sivujen määrä: 10
ISSN: 0197-4580
eISSN: 1558-1497
DOI: https://doi.org/10.1016/j.neurobiolaging.2018.05.013
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/34270955
Contradictory findings on the role of the type 1 cannabinoid receptor (CB1R) during the pathogenesis of Alzheimer's disease (AD) have been reported. Here, we evaluated the CB1R brain profile in an AD mouse model using longitudinal positron emission tomography with an inverse agonist for CB1R, [F-18]FMPEP-d(2). APP/PS1-21 and wild-type (n = 8 in each group) mice were repeatedly imaged between 6 to 15 months of age, accompanied by brain autoradiography, western blot, and CB1R immunohistochemistry with additional mice. [F-18]FMPEP-d(2) positron emission tomography demonstrated lower (p < 0.05) binding ratios in the parietotemporal cortex and hippocampus of APP/PS1-21 mice compared with age-matched wild-type mice. Western blot demonstrated no differences between APP/PS1-21 and wild-type mice in the CB1R abundance, whereas significantly lower (p < 0.05) receptor expression was observed in male than female mice. The results provide the first demonstration that [F-18]FMPEP-d(2) is a promising imaging tool for AD research in terms of CB1R availability, but not expression. This finding may further facilitate the development of novel therapeutic approaches based on endocannabinoid regulation. (C) 2018 The Authors. Published by Elsevier Inc.
Ladattava julkaisu This is an electronic reprint of the original article. |