Title
No effects of PCSK9-inhibitor treatment on spatial learning, locomotor activity, and novel object recognition in mice
Author
Schlunk, F.
Fisher, P.
Princen, H.M.G.
Rex, A.
Prinz, V.
Foddis, M.
Lütjohann, D.
Laufs, U.
Endres, M.
Publication year
2021
Abstract
Monoclonal anti-proprotein convertase subtilisin/kexin type 9 (PSCK9) neutralizing antibodies effectively lower plasma cholesterol levels and decrease cardiovascular events but also raised some concern that cognitive function could worsen as a side effect. Here, we performed experiments in mice to characterize the effect of anti-PCSK9 antibodies on behavior and cognitive function in detail. APOE*3Leiden.CETP mice and B6129SF1/J wildtype mice were fed a Western type diet and treated with the fully human anti-PCSK9 antibody CmAb1 (PL-45134; 10mg*kg-1 s.c.) or vehicle for 6 weeks. Locomotor activity, anxiety levels, recognition memory, and spatial learning were investigated using the open field, novel object recognition test, and Morris water maze, respectively. Serum cholesterol levels in APOE*3Leiden.CETP mice after treatment with anti-PCSK9 antibody were significantly lower compared to controls whereas cholesterol levels in B6129SF1/J wildtype mice remained unchanged at low levels. No apparent differences were found regarding locomotor activity, anxiety, recognition memory, and spatial learning between animals treated with anti-PCSK9 antibody or vehicle in APOE*3Leiden.CETP and B6129SF1/J wildtype mice. In this study, we found no evidence that treatment with anti-PCSK9 antibodies lead to differences in behavior or changes of cognition in mice.
Subject
Life
MHR - Metabolic Health Research
ELSS - Earth, Life and Social Sciences
Biomedical Innovation
Healthy Living
Cognitition
Animal research
PCSK9-inhibitors
Cholesterol
Behaviour
To reference this document use:
http://resolver.tudelft.nl/uuid:54a064ac-62fe-44ec-a6b6-1b2152d34cfa
DOI
https://doi.org/10.1016/j.bbr.2020.112875
TNO identifier
880213
Source
Behavioral Brain Research, 396
Article number
112875
Document type
article