title: A potential role for the acid-sensing T cell death associated gene-8 (TDAG8) receptor in depression-like behavior.
abstract: Inflammation has been suggested to contribute to the pathophysiology of depression. The T cell death associated gene-8 (TDAG8) receptor is a proton-sensing G-protein-coupled receptor (GPCR) expressed on immune cells in both the CNS and periphery. Previous work has shown modulation of inflammation by the TDAG8 receptor, with pro-inflammatory responses reported in the central nervous system (CNS). Given the link between depression and inflammation, the aim of the present study was to investigate the role of TDAG8 in depression relevant behaviors. Mice deficient in TDAG8 (TDAG8(-/-)) were tested in the forced swim test (FST) and sucrose preference paradigm. TDAG8 deficiency resulted in significant attenuation of immobility in the FST as compared to wild type TDAG8 (TDAG8(+/+)) mice. These differences were not due to alterations in motor activity evoked by TDAG8 deficiency as TDAG8(+/+) and TDAG8(-/-) mice displayed similar activity in the home cage or in a novel context. TDAG8(-/-) mice showed significantly higher consumption of sucrose compared to wild type mice although sucrose preference was not significantly different between genotypes. Collectively, our results support the involvement of the TDAG8 receptor in behavioral response relevant to depression. Further investigation is required to validate TDAG8 as a novel target linking inflammation and depression.
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, College of Medicine, Cincinnati, OH 45219, United States. Electronic address: larkeln@uc.edu.
authors.forename: Lauren Larke
authors.initials: LL
authors.lastname: Vollmer
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, College of Medicine, Cincinnati, OH 45219, United States.
authors.forename: Sarah N
authors.initials: SN
authors.lastname: Schmeltzer
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, College of Medicine, Cincinnati, OH 45219, United States.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Ahlbrand
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, College of Medicine, Cincinnati, OH 45219, United States; VA Medical Centre, Cincinnati, OH 45237, United States.
authors.forename: Renu
authors.initials: R
authors.lastname: Sah
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003863:Depression / Q000235:genetics* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004326:Drinking / Q000235:genetics; D004435:Eating / Q000235:genetics; D005518:Food Preferences; D049452:Green Fluorescent Proteins / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D013395:Sucrose / Q000008:administration & dosage; D013549:Sweetening Agents / Q000008:administration & dosage; D013550:Swimming / Q000523:psychology
chemical_list: C513337:GPR65 protein, mouse; D043562:Receptors, G-Protein-Coupled; D013549:Sweetening Agents; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D013395:Sucrose
keywords: Behavior; Depression; T cell death associated gene-8; TDAG8