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Open AccessArticle

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

1
Department of Life Science, National Taiwan University, Taipei 11221, Taiwan
2
Department of Chemistry, Chung Yuan Christian University, Chung-Li 32023, Taiwan
3
Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li 32023, Taiwan
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Department of Biomedical Engineering, Chung Yuan Christian University, Chung-Li 32023, Taiwan
5
Department of Pediatrics, Taipei Veterans General Hospital, Taipei 11221, Taiwan
6
School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan
7
School of Medicine, National Defense Medical Center, Taipei 11490, Taiwan
8
Center for nanotechnology, Chung Yuan Christian University, Chung-Li 32023, Taiwan
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(8), 2837; https://doi.org/10.3390/ijms21082837
Received: 16 March 2020 / Revised: 15 April 2020 / Accepted: 16 April 2020 / Published: 18 April 2020
(This article belongs to the Special Issue Zebrafish Models of Neurological Diseases and Disorders)
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. View Full-Text
Keywords: zebrafish; anxiety; memory; circadian rhythm locomotor activity; behavior; lysophosphatidic acid receptor zebrafish; anxiety; memory; circadian rhythm locomotor activity; behavior; lysophosphatidic acid receptor
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Lin, Y.-N.; Audira, G.; Malhotra, N.; Ngoc Anh, N.T.; Siregar, P.; Lu, J.-H.; Lee, H.; Hsiao, C.-D. A Novel Function of the Lysophosphatidic Acid Receptor 3 (LPAR3) Gene in Zebrafish on Modulating Anxiety, Circadian Rhythm Locomotor Activity, and Short-Term Memory. Int. J. Mol. Sci. 2020, 21, 2837.

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