Aplnr knockout mice display sex-specific changes in conditioned fear

The G-protein-coupled receptor APLNR and its ligands apelin and ELABELA/TODDLER/apela comprise the apelinergic system, a signaling pathway that is critical during development and physiological homeostasis. Targeted regulation of the receptor has been proposed to treat several important diseases including heart failure, pulmonary arterial hypertension and metabolic syndrome. The apelinergic system is widely expressed within the central nervous system (CNS). However, the role of this system in the CNS has not been completely elucidated. Utilizing an Aplnr knockout mouse model, we report here results from tests of sensory ability, locomotion, reward preference, social preference, learning and memory, and anxiety. We find that knockout of Aplnr leads to significant effects on acoustic startle response and sex-specific effects on conditioned fear responses without significant changes in baseline anxiety. In particular, male Aplnr knockout mice display enhanced context- and cue-dependent fear responses. Our results complement previous reports that exogenous Apelin administration reduced conditioned fear and freezing responses in rodent models, and future studies will explore the therapeutic benefit of APLNR-targeted drugs in rodent models of PTSD.

Automated summary

The G-protein-coupled receptor APLNR, along with its ligands apelin and ELABELA/TODDLER/apela, form the apelinergic system crucial for development and physiological balance, potentially offering treatment for heart failure, pulmonary arterial hypertension, and metabolic syndrome. While widely present in the central nervous system, its exact role remains unclear. Knockout of the Aplnr gene in mice showed significant impacts on sensory responses and fear behaviors, especially in male mice displaying heightened fear responses.