Journal
BEHAVIOURAL BRAIN RESEARCH
Volume 396, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.bbr.2020.112875
Keywords
cognitition; animal research; PCSK9-inhibitors; cholesterol; behaviour
Categories
Funding
- Charite - Universitatsmedizin Berlin
- Berlin Institute of Health
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In this mouse study, treatment with anti-PCSK9 antibodies did not lead to differences in behavior or changes in cognition.
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*3-Leiden. 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.
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