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.
Highlights
Lysophosphatidic acid, a phospholipid, is a mediator for many biological and physiological processes such as cell differentiation, cell proliferation, cell-to-cell interactions, smooth muscle contraction, and platelet aggregation [1,2]
Lpar3 KO fish displayed impairments in several behaviors, including hyperactivity-like behavior in the larvae stage and altered exploratory behavior, social interaction, and circadian rhythm locomotor activity in the adult stage. These findings strongly suggest that the LPAR3 receptor is involved in larval and adult zebrafish behavior
The latency after the training day of lpar3 KO fish was significantly decreased compared to the WT fish, which showed no difference (Figure 7C). These results clearly indicate that lpar3 deficiency could be related to short-term memory impairment in adult zebrafish
Summary
Lysophosphatidic acid, a phospholipid, is a mediator for many biological and physiological processes such as cell differentiation, cell proliferation, cell-to-cell interactions, smooth muscle contraction, and platelet aggregation [1,2]. The expression pattern and signaling properties of LPARs are complex and result in multiple influences on physiological, pathological, and developmental processes, which in turn act through G protein-coupled receptors (GPCRs). Activation of lpar suppressed thrombopoiesis in zebrafish, blocked lpar translation by a morpholino increase in the number of CD41-GFP cells in transgenic zebrafish, and increased ZCD41 mRNA expression levels of lpar knockout zebrafish These results signify the negative impact of lpar during megakaryopoiesis and might help in providing potential treatment of related diseases [23]. Lpar KO fish displayed impairments in several behaviors, including hyperactivity-like behavior in the larvae stage and altered exploratory behavior, social interaction, and circadian rhythm locomotor activity in the adult stage These findings strongly suggest that the LPAR3 receptor is involved in larval and adult zebrafish behavior
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
