ORIGINAL RESEARCH article
Front. Neurosci.
Sec. Neurodevelopment
Effects of GPR110 expression on neurobehavioral outcomes in mice
Provisionally accepted
- National Institutes of Health, Bethesda, United States
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The adhesion G Protein-Coupled Receptor 110 (GPR110) is highly expressed in brain during development. Although its level is broadly reduced in adulthood, GPR110 expression notably persists in the hippocampus, yet its role in adult neurobehavioral function remains incompletely defined. In this study, we investigated whether altering GPR110 levels affects behavior and associated molecular pathways in adult mice. Using mice with global deletion of GPR110 and mice with Cre-dependent overexpression of GPR110 in glutamatergic neurons, we performed behavioral testing and transcriptomic and proteomic analyses of hippocampal and cortical tissue. Global deletion of GPR110 led to increased immobility in the open field test and impaired learning and memory, accompanied by downregulation of genes and proteins involved in synaptogenesis, neurotransmission, glutamatergic signaling, and neuronal development. In contrast, overexpression of GPR110 selectively in glutamatergic neurons reduced anxiety-and compulsive-like behaviors with enhanced receptor-mediated signaling and proteins linked to neuronal morphogenesis and synaptic communication. Together, these findings demonstrate that GPR110 regulates anxiety-related and cognitive behaviors in adult mice and modulates synaptic and signaling pathways that support neuronal structure and communication. The GPR110-dependent mechanism as a new target for neurobehavioral modulation may provide a strategy to mitigate anxiety-and cognition-related pathophysiologic behavioral conditions.
Keywords: Anxiety, GPR110, Hippocampus, learning and memory, Proteomics
Received: 23 Dec 2025; Accepted: 13 Feb 2026.
Copyright: © 2026 Melkumyan, Huang, Toro, Kenser and Kim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Mariam Melkumyan
Hee-Yong Kim
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