A Novel Function of the Lysophosphatidic Acid Receptor 3 (LPAR3) Gene in Zebrafish on Modulating Anxiety, Circadian Rhythm Locomotor Activity, and Short-Term Memory

Abstract

Lysophosphatidic acid (LPA) is a small lysophospholipid molecule that activates multiple cellular functions through pathways with G-protein-coupled receptors. So far, six LPA receptors (LPAR1 to LPAR6) have been discovered and each one of them can connect to the downstream cell message-transmitting network. A previous study demonstrated that LPA receptors found in blood-producing stem cells can enhance erythropoietic processes through the activation of LPAR3. In the current study, newly discovered functions of LPAR3 were identified through extensive behavioral tests in lpar3 knockout (KO) zebrafish. It was found that the adult lpar3 KO zebrafish display an abnormal movement orientation and altered exploratory behavior compared to that of the control group in the three-dimensional locomotor and novel tank tests, respectively. Furthermore, consistent with those results, in the circadian rhythm locomotor activity test, the lpar3 KO zebrafish showed a lower level of angular velocity and average speed during the light cycles, indicating an hyperactivity-like behavior. In addition, the mutant fish also exhibited considerably higher locomotor activity during the dark cycle. Supporting those findings, this phenomenon was also displayed in the lpar3 KO zebrafish larvae. Furthermore, several important behavior alterations were also observed in the adult lpar3 KO fish, including a lower degree of aggression, less interest in conspecific social interaction, and looser shoal formation. However, there was no significant difference regarding the predator avoidance behavior between the mutant and the control fish. In addition, lpar3 KO zebrafish displayed memory deficiency in the passive avoidance test. These in vivo results support for the first time that the lpar3 gene plays a novel role in modulating behaviors of anxiety, aggression, social interaction, circadian rhythm locomotor activity, and memory retention in zebrafish.

Transcriptomics Changes in the Peritoneum of Mice with Lipopolysaccharide-Induced Peritonitis

“…The protein is involved in the GPCR signaling and peptide ligand-binding receptor pathway. Furthermore, LPAR3 is associated with Tracheal cancer and Trachea Adenoid Cystic Carcinoma [ 31 ].…”

Waterborne Exposure of Paclobutrazol at Environmental Relevant Concentration Induce Locomotion Hyperactivity in Larvae and Anxiolytic Exploratory Behavior in Adult Zebrafish

“…However, the visible light was switched on after every 10 min for the light cycle, and then switched off for the dark period. Later we did the behavioral assay such as total distance covered, turning frequency, and bursts during every 10 mints of the dark and light cycle using the ZebraBox instrument equipped with infrared camera and their tracking extension software system according to a previous protocol [ 39 , 40 , 41 ]. A total of 80 min of recording with swimming data were collected.…”

Shared biological mechanisms of depression and obesity: focus on adipokines and lipokines

“…In the hippocampus, genetic deletion of Lpar1 leads to more immature dendritic spines in CA1 pyramidal cells and reduces matrix metalloproteinase 9 (MMP-9), which has been proven to be engaged in regulating synaptic plasticity [ 243 ]. In zebrafish in vivo experiments, the Lpar3 gene exerts novel roles in regulating behaviors such as anxiety, social interactions, circadian rhythmic motor activity, and memory retention [ 244 ]. Gintonin, an exogenous LPA receptor ligand, was isolated from P. ginseng.…”