{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T21:29:43Z","timestamp":1785792583779,"version":"3.56.0"},"reference-count":17,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnins.2026.1774433","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T14:10:56Z","timestamp":1772633456000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Effects of GPR110 expression on neurobehavioral outcomes in mice"],"prefix":"10.3389","volume":"20","author":[{"given":"Mariam","family":"Melkumyan","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Signaling, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health","place":["Rockville, MD, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bill X.","family":"Huang","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Signaling, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health","place":["Rockville, MD, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Toro","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Signaling, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health","place":["Rockville, MD, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Kesner","sequence":"additional","affiliation":[{"name":"Unit on Motivation and Arousal, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health","place":["Rockville, MD, United States"]},{"name":"Department of Psychology, Indiana University - Indianapolis","place":["Indianapolis, IN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee-Yong","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Signaling, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health","place":["Rockville, MD, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1186\/s12974-023-02868-w","article-title":"Exacerbating effects of single-dose acute ethanol exposure on neuroinflammation and amelioration by GPR110 (ADGRF1) activation","volume":"20","author":"Banerjee","year":"2023","journal-title":"J. Neuroinflammation"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1111\/j.1471-4159.2009.06335.x","article-title":"Docosahexaenoic acid promotes hippocampal neuronal development and synaptic function","volume":"111","author":"Cao","year":"2009","journal-title":"J. Neurochem."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1186\/s12974-021-02195-y","article-title":"GPR110 ligands reduce chronic optic tract gliosis and visual deficit following repetitive mild traumatic brain injury in mice","volume":"18","author":"Chen","year":"2021","journal-title":"J. Neuroinflammation"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"2321","DOI":"10.1038\/s41380-024-02456-1","article-title":"Enhanced fear memory after social defeat in mice is dependent on interleukin-1 receptor signaling in glutamatergic neurons","volume":"29","author":"Goodman","year":"2024","journal-title":"Mol. Psychiatry"},{"key":"ref9001","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1038\/s42003-020-0831-6","article-title":"Synaptamide activates the adhesion GPCR GPR110 (ADGRF1) through GAIN domain binding","volume":"3","author":"Huang","year":"2020","journal-title":"Commun Biol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"102691","DOI":"10.1016\/j.xpro.2023.102691","article-title":"Protocol for identifying physiologically relevant binding proteins of G-protein-coupled receptors","volume":"4","author":"Huang","year":"2023","journal-title":"STAR Protocols"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"ENEURO.0319-21.2021","DOI":"10.1523\/ENEURO.0319-21.2021","article-title":"Promoting and optimizing the use of 3D-printed objects in spontaneous recognition memory tasks in rodents: a method for improving rigor and reproducibility","volume":"8","author":"Inayat","year":"2021","journal-title":"eNeuro"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"5340","DOI":"10.3390\/ijms24065340","article-title":"Ligand-induced activation of GPR110 (ADGRF1) to improve visual function impaired by optic nerve injury","volume":"24","author":"Kwon","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"3386","DOI":"10.3390\/ijms22073386","article-title":"Ligand-induced GPR110 activation facilitates axon growth after injury","volume":"22","author":"Kwon","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"13123","DOI":"10.1038\/ncomms13123","article-title":"Orphan GPR110 (ADGRF1) targeted by N-docosahexaenoylethanolamine in development of neurons and cognitive function","volume":"7","author":"Lee","year":"2016","journal-title":"Nat. Commun."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"107385","DOI":"10.1016\/j.isci.2023.107385","article-title":"Ventral pallidal glutamatergic neurons regulate wakefulness and emotion through separated projections","volume":"26","author":"Luo","year":"2023","journal-title":"iScience"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1671","DOI":"10.1038\/s41380-022-01858-3","article-title":"Ventral tegmental area glutamate neurons mediate nonassociative consequences of stress","volume":"29","author":"McGovern","year":"2024","journal-title":"Mol. Psychiatry"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"144","DOI":"10.3109\/03009734.2015.1032454","article-title":"Targeted deletion of VGluT2 expression in the embryonal telencephalon promotes an anxiolytic phenotype of the adult mouse","volume":"120","author":"Nordenankar","year":"2015","journal-title":"Ups. J. Med. Sci."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1186\/s12974-019-1621-2","article-title":"GPR110 (ADGRF1) mediates anti-inflammatory effects of N-docosahexaenoylethanolamine","volume":"16","author":"Park","year":"2019","journal-title":"J. Neuroinflammation"},{"key":"ref09","doi-asserted-by":"publisher","first-page":"D543","DOI":"10.1093\/nar\/gkae1011","article-title":"The PRIDE database at 20 years: 2025 update","volume":"53","author":"Perez-Riverol","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"146","DOI":"10.3389\/fnbeh.2018.00146","article-title":"Eliminating the VGluT2-dependent glutamatergic transmission of Parvalbumin-expressing neurons leads to deficits in locomotion and vocalization, decreased pain sensitivity, and increased dominance","volume":"12","author":"Roccaro-Waldmeyer","year":"2018","journal-title":"Front. Behav. Neurosci."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.neuron.2011.05.028","article-title":"Leptin action on GABAergic neurons prevents obesity and reduces inhibitory tone to POMC neurons","volume":"71","author":"Vong","year":"2011","journal-title":"Neuron"}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2026.1774433\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T14:10:57Z","timestamp":1772633457000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2026.1774433\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,4]]},"references-count":17,"alternative-id":["10.3389\/fnins.2026.1774433"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2026.1774433","relation":{},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,4]]},"article-number":"1774433"}}