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Updated: Dec 10, 2025
Novel Object Recognition Test for the Investigation of Learning and Memory in Mice
Published on: August 30, 2017
No effects of PCSK9-inhibitor treatment on spatial learning, locomotor activity, and novel object recognition in mice
Frieder Schlunk1, Paul Fischer2, Hans M G Princen3
1Klinik und Hochschulambulanz für Neurologie mit Abteilung für Experimentelle Neurologie, Center for Stroke Research Berlin (CSB), and NeuroCure, Charité University Medicine Berlin, Germany; Department of Neuroradiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
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.
Insights
Monoclonal anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies effectively lower cholesterol but may impact cognition. This study found no evidence of behavioral or cognitive changes in mice treated with anti-PCSK9 antibodies.
Area of Science:
- Neuroscience
- Cardiovascular Pharmacology
- Immunology
Background:
- Monoclonal anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) neutralizing antibodies are effective in reducing plasma cholesterol and cardiovascular events.
- Concerns have been raised regarding potential adverse effects of these antibodies on cognitive function.
Purpose of the Study:
- To investigate the effects of anti-PCSK9 antibodies on behavior and cognitive function in mice.
- To determine if anti-PCSK9 antibody treatment influences locomotor activity, anxiety, recognition memory, or spatial learning.
Main Methods:
- APOE*3Leiden.CETP and B6129SF1/J wildtype mice were fed a Western diet and treated with an anti-PCSK9 antibody (CmAb1) or vehicle for 6 weeks.
- Behavioral and cognitive functions were assessed using the open field test, novel object recognition test, and Morris water maze.
- Serum cholesterol levels were measured to confirm antibody efficacy.
Main Results:
- Anti-PCSK9 antibody treatment significantly lowered serum cholesterol in APOE*3Leiden.CETP mice but not in B6129SF1/J wildtype mice.
- No significant differences in locomotor activity, anxiety levels, recognition memory, or spatial learning were observed between anti-PCSK9 antibody-treated and vehicle-treated groups in either mouse model.
- These findings indicate no adverse effects on behavior or cognition.
Conclusions:
- Treatment with anti-PCSK9 antibodies did not lead to observable differences in behavior or cognitive function in the studied mouse models.
- This study provides evidence that anti-PCSK9 antibodies do not negatively impact cognitive processes in mice.
- Further research may be warranted to fully elucidate the long-term neurological effects of PCSK9 inhibition.
