Digital autoradiography for efficient functional imaging without anesthesia in experimental animals : Reversing phencyclidine-induced functional alterations using clozapine

Autoradiography (ARG) is a high-resolution imaging method for localization of radiolabeled biomarkers in ex vivo specimen. ARG using 2-deoxy-D-glucose (2-DG) method is used in to study drug actions on brain functional activity, as it provides results comparable to clinically used functional positron-emission tomography (PET). The requirement of slow analog detection methods and emerging advances in small animal PET imaging have, however, reduced the interest in ARG. In contrast to ARG, experimental animals need to be restrained or sedated/anesthetized for PET imaging, which strongly influence functional activity and thus complicate the interpretation of the results. Digital direct particle-counting ARG systems have gained attraction during the last decade to overcome the caveats of conventional ARG methods. Here we demonstrate that the well-established 2-DG imaging method can be adapted into use with contemporary digital detectors. This method readily and rapidly captures the characteristic effects of phencyclidine (5 mg/kg, i.p.), a dissociative agent targeting the NMDAR (N-methyl-D-aspartate receptor), on regional glucose utilization in the adult mouse brain. Pretreatment with antipsychotic drug clozapine (6 mg/kg, i.p.) essentially abolishes these effects of phencyclidine on brain functional activity. Digital ARG produces viable data for the regional analysis of functional activity in a fraction of time required for film development. These results support the use of digital ARG in preclinical drug research, where high throughput and response linearity are preferred and use of sedation/anesthesia has to be avoided.Peer reviewe

Improved synthesis of [18F] fallypride and characterization of a Huntington’s disease mouse model, zQ175DN KI, using longitudinal PET imaging of D2/D3 receptors

Dopamine receptors are involved in pathophysiology of neuropsychiatric diseases, including Huntington’s disease (HD). PET imaging of dopamine D2 receptors (D2R) in HD patients has demonstrated 40% decrease in D2R binding in striatum, and D2R could be a reliable quantitative target to monitor disease progression. A D2/3R antagonist, [18F] fallypride, is a high-affinity radioligand that has been clinically used to study receptor density and occupancy in neuropsychiatric disorders. Here we report an improved synthesis method for [18F]fallypride. In addition, high molar activity of the ligand has allowed us to apply PET imaging to characterize D2/D3 receptor density in striatum of the recently developed zQ175DN knock-in (KI) mouse model of HD.Peer reviewe

Inaugural Charles River World Congress on Animal Models in Drug Discovery and Development

https://deepblue.lib.umich.edu/bitstream/2027.42/138112/1/12967_2017_Article_1274.pd

Native and Complexed IGF-1: Biodistribution and Pharmacokinetics in Infantile Neuronal Ceroid Lipofuscinosis

Infantile neuronal ceroid lipofuscinosis (INCL) is a severe neurodegenerative disorder of childhood characterized by selective death of cortical neurons. Insulin-like growth factor 1 (IGF-1) is important in embryonic development and is considered as a potential therapeutic agent for several disorders of peripheral and central nervous systems. In circulation IGF-1 is mainly bound to its carrier protein IGFBP-3. As a therapeutic agent IGF-1 has shown to be more active as free than complexed form. However, this may cause side effects during the prolonged treatment. In addition to IGFBP-3 the bioavailability of IGF-1 can be modulated by using mesoporous silicon nanoparticles (NPs) which are optimal carriers for sustained release of unstable peptide hormones like IGF-1. In this study we compared biodistribution, pharmacokinetics, and bioavailability of radiolabeled free IGF-1, IGF-1/IGFBP-3, and IGF-1/NP complexes in a Cln1-/- knockout mouse model. IGF-1/NP was mainly accumulated in liver and spleen in all studied time points, whereas minor and more constant amounts were measured in other organs compared to free IGF-1 or IGF-1/IGFBP-3. Also concentration of IGF-1/NP in blood was relatively high and stable during studied time points suggesting continuous release of IGF-1 from the particles

Kohti kasvipainotteisia ruokavalintoja. Työkirja ruokapalveluille

Ruokapalvelut ovat ottaneet haasteen lisätä kasvisruokatarjontaa vauhdilla vastaan ja kehittävät innokkaasti uutta reseptiikkaa asiakkaita kuunnellen. Ilmasto- ja ravitsemussyistä kasvipainotteinen ruoka on tulevaisuuden ykkösruokavaihtoehto. Moniammatillinen yhteistyö julkisissa ruokapalveluissa ja ruokapalveluiden toisiltaan saama vertaistuki toimivat pilareina kasvipainotteisuuden ja kasvisruokamyönteisyyden edistämisessä. Yhteistyö lisää keskinäistä ymmärrystä ja luottamusta, sujuvoittaa arjen toimintaa sekä moninkertaistaa osaamispääomaa kasvipainotteista ruokatarjontaa lisättäessä. Kohti kasvipainotteisia ruokavalintoja -työkirja on rakentunut KasvisPro-koulutushankkeessa toteutettujen käytännön koulutusten ja verkkotyöpajojen materiaalien sekä koulutukseen osallistuneiden ruokapalvelutoimijoiden esittämien hyvien käytänteiden pohjalta. Työkirjasta löytyy kasvisruokatietoutta sekä käytännön ohjeita ja vinkkilistoja kasvipainotteisen ruokailun edistämiseen julkisissa ruokapalveluissa