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Journal of Neural Transmission

Erschienen in:

01.03.2015 | Psychiatry and Preclinical Psychiatric Studies - Original Article

Lysophosphatidic acid induces anxiety-like behavior via its receptors in mice

verfasst von: Misa Yamada, Mai Tsukagoshi, Tomio Hashimoto, Jun-Ichiro Oka, Akiyoshi Saitoh, Mitsuhiko Yamada

Erschienen in: Journal of Neural Transmission | Ausgabe 3/2015

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Abstract

Lysophosphatidic acid (LPA) is a potent bioactive lipid mediator with diverse biological properties. We previously found altered expression of the LPA-related genes in rodents after treatment with sertraline, which is widely used to treat anxiety disorders and depression. However, little is known about the behavioral effects of LPA. In the present study, we investigated the behavioral effects of intracerebroventricular injection of LPA in adult mice. LPA did not significantly affect spontaneous locomotor activity, suggesting that LPA does not induce hyperactivity, ataxia, or sedation. We next investigated the emotional effects of LPA via the hole-board test. LPA significantly increased the number of head-dips in a dose- and time-related manner. A significant induction of head-dip counts occurred 15 and 30 min after LPA administration. To clarify the involvement of LPA receptors, we examined the effect of the non-selective LPA1-4 receptor antagonist, 1-bromo-3(S)-hydroxy-4-(palmitoyloxy)butyl-phosphonate (BrP-LPA) co-administered with LPA. BrP-LPA dose-dependently inhibited LPA-induced head-dip counts. We next investigated anxiety-like behavior via the elevated plus-maze test. LPA significantly reduced the percentage of time spent in the open arms and BrP-LPA dose-dependently inhibited this anxiety-like behavior. In conclusion, LPA induced anxiety-like behavior in mice via LPA receptors. Our results suggest that LPA signaling plays an important role in regulating anxiety in mice.

Brauer AU, Savaskan NE, Kuhn H, Prehn S, Ninnemann O, Nitsch R (2003) A new phospholipid phosphatase, PRG-1, is involved in axon growth and regenerative sprouting. Nat Neurosci 6(6):572–578. doi:10.1038/nn1052 CrossRefPubMed

Brecher P (1983) The interaction of long-chain acyl CoA with membranes. Mol Cell Biochem 57(1):3–15CrossRefPubMed

Callaerts-Vegh Z, Leo S, Vermaercke B, Meert T, D’Hooge R (2012) LPA(5) receptor plays a role in pain sensitivity, emotional exploration and reversal learning. Genes Brain, Behav 11(8):1009–1019. doi:10.1111/j.1601-183X.2012.00840.x

Castilla-Ortega E, Hoyo-Becerra C, Pedraza C, Chun J, Rodriguez De Fonseca F, Estivill-Torrus G, Santin LJ (2011) Aggravation of chronic stress effects on hippocampal neurogenesis and spatial memory in LPA(1) receptor knockout mice. PLoS One 6(9):e25522. doi:10.1371/journal.pone.0025522 CrossRefPubMedCentralPubMed

Castilla-Ortega E, Escuredo L, Bilbao A, Pedraza C, Orio L, Estivill-Torrus G, Santin LJ, de Fonseca FR, Pavon FJ (2014) 1-Oleoyl lysophosphatidic acid: a new mediator of emotional behavior in rats. PLoS One 9(1):e85348. doi:10.1371/journal.pone.0085348 CrossRefPubMedCentralPubMed

Choi JW, Chun J (2013) Lysophospholipids and their receptors in the central nervous system. Biochim Biophys Acta 1831 1:20–32. doi:10.1016/j.bbalip.2012.07.015 CrossRef

Choi JW, Herr DR, Noguchi K, Yung YC, Lee CW, Mutoh T, Lin ME, Teo ST, Park KE, Mosley AN, Chun J (2010) LPA receptors: subtypes and biological actions. Annu Rev Pharmacol Toxicol 50:157–186. doi:10.1146/annurev.pharmtox.010909.105753 CrossRefPubMed

Fedorova I, Hussein N, Di Martino C, Moriguchi T, Hoshiba J, Majchrzak S, Salem N Jr (2007) An n-3 fatty acid deficient diet affects mouse spatial learning in the barnes circular maze. Prostaglandins Leukot Essent Fatty Acids 77(5–6):269–277. doi:10.1016/j.plefa.2007.10.013 CrossRefPubMedCentralPubMed

Haley TJ, McCormick WG (1957) Pharmacological effects produced by intracerebral injection of drugs in the conscious mouse. Bri J Pharmacol Chemother 12(1):12–15CrossRef

Ishii I, Fukushima N, Ye X, Chun J (2004) Lysophospholipid receptors: signaling and biology. Annu Rev Biochem 73:321–354. doi:10.1146/annurev.biochem.73.011303.073731 CrossRefPubMed

Iwai T, Saitoh A, Yamada M, Takahashi K, Hashimoto E, Ukai W, Saito T, Yamada M (2012) Rhotekin modulates differentiation of cultured neural stem cells to neurons. J Neurosci Res 90(7):1359–1366. doi:10.1002/jnr.23029 CrossRefPubMed

Karliner JS (2004) Mechanisms of cardioprotection by lysophospholipids. J Cell Biochem 92(6):1095–1103. doi:10.1002/jcb.20129 CrossRefPubMed

Maekawa M, Ishizaki T, Boku S, Watanabe N, Fujita A, Iwamatsu A, Obinata T, Ohashi K, Mizuno K, Narumiya S (1999) Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase. Science (New York, NY) 285(5429):895–898CrossRef

Ocana M, Del Pozo E, Baeyens JM (1993) ATP-dependent K+ channel blockers antagonize morphine- but not U-504,88H-induced antinociception. Eur J Pharmacol 230(2):203–207CrossRefPubMed

Panupinthu N, Lee HY, Mills GB (2010) Lysophosphatidic acid production and action: critical new players in breast cancer initiation and progression. Br J Cancer 102(6):941–946. doi:10.1038/sj.bjc.6605588 CrossRefPubMedCentralPubMed

Pedraza C, Sanchez-Lopez J, Castilla-Ortega E, Rosell-Valle C, Zambrana-Infantes E, Garcia-Fernandez M, Rodriguez de Fonseca F, Chun J, Santin LJ, Estivill-Torrus G (2013) Fear extinction and acute stress reactivity reveal a role of LPA receptor in regulating emotional-like behaviors. Brain Struct Func. doi:10.1007/s00429-013-0592-9

Reed TT (2011) Lipid peroxidation and neurodegenerative disease. Free Radic Biol Med 51(7):1302–1319. doi:10.1016/j.freeradbiomed.2011.06.027 CrossRefPubMed

Saitoh A, Hirose N, Yamada M, Yamada M, Nozaki C, Oka T, Kamei J (2006a) Changes in emotional behavior of mice in the hole-board test after olfactory bulbectomy. J Pharmacol Sci 102(4):377–386CrossRefPubMed

Saitoh A, Yamada M, Yamada M, Kobayashi S, Hirose N, Honda K, Kamei J (2006b) ROCK inhibition produces anxiety-related behaviors in mice. Psychopharmacology 188(1):1–11. doi:10.1007/s00213-006-0466-4 CrossRefPubMed

Saitoh A, Yamaguchi K, Tatsumi Y, Murasawa H, Nakatani A, Hirose N, Yamada M, Yamada M, Kamei J (2007) Effects of milnacipran and fluvoxamine on hyperemotional behaviors and the loss of tryptophan hydroxylase-positive cells in olfactory bulbectomized rats. Psychopharmacology 191(4):857–865. doi:10.1007/s00213-007-0699-x CrossRefPubMed

Saitoh A, Yamada M, Yamada M, Takahashi K, Yamaguchi K, Murasawa H, Nakatani A, Tatsumi Y, Hirose N, Kamei J (2008) Antidepressant-like effects of the delta-opioid receptor agonist SNC80 ([(+)-4-[(alphaR)-alpha-[(2S,5R)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-me thoxyphenyl)methyl]-N, N-diethylbenzamide) in an olfactory bulbectomized rat model. Brain Res 1208:160–169. doi:10.1016/j.brainres.2007.07.095 CrossRefPubMed

Santin LJ, Bilbao A, Pedraza C, Matas-Rico E, Lopez-Barroso D, Castilla-Ortega E, Sanchez-Lopez J, Riquelme R, Varela-Nieto I, de la Villa P, Suardiaz M, Chun J, De Fonseca FR, Estivill-Torrus G (2009) Behavioral phenotype of maLPA1-null mice: increased anxiety-like behavior and spatial memory deficits. Genes Brain Behav 8(8):772–784. doi:10.1111/j.1601-183X.2009.00524.x CrossRefPubMed

Swaney JS, Chapman C, Correa LD, Stebbins KJ, Bundey RA, Prodanovich PC, Fagan P, Baccei CS, Santini AM, Hutchinson JH, Seiders TJ, Parr TA, Prasit P, Evans JF, Lorrain DS (2010) A novel, orally active LPA(1) receptor antagonist inhibits lung fibrosis in the mouse bleomycin model. Br J Pharmacol 160(7):1699–1713. doi:10.1111/j.1476-5381.2010.00828.x CrossRefPubMedCentralPubMed

Takeda H, Tsuji M, Matsumiya T (1998) Changes in head-dipping behavior in the hole-board test reflect the anxiogenic and/or anxiolytic state in mice. Eur J Pharmacol 350(1):21–29CrossRefPubMed

Vinot N, Jouin M, Lhomme-Duchadeuil A, Guesnet P, Alessandri JM, Aujard F, Pifferi F (2011) Omega-3 fatty acids from fish oil lower anxiety, improve cognitive functions and reduce spontaneous locomotor activity in a non-human primate. PLoS One 6(6):e20491. doi:10.1371/journal.pone.0020491 CrossRefPubMedCentralPubMed

Yamada M, Higuchi T (2002) Functional genomics and depression research. Beyond the monoamine hypothesis. Eur Neuropsychopharmacol 12(3):235–244 (the journal of the European College of Neuropsychopharmacology)CrossRefPubMed

Ye X, Hama K, Contos JJ, Anliker B, Inoue A, Skinner MK, Suzuki H, Amano T, Kennedy G, Arai H, Aoki J, Chun J (2005) LPA3-mediated lysophosphatidic acid signalling in embryo implantation and spacing. Nature 435(7038):104–108. doi:10.1038/nature03505 CrossRefPubMedCentralPubMed

Zhang H, Xu X, Gajewiak J, Tsukahara R, Fujiwara Y, Liu J, Fells JI, Perygin D, Parrill AL, Tigyi G, Prestwich GD (2009) Dual activity lysophosphatidic acid receptor pan-antagonist/autotaxin inhibitor reduces breast cancer cell migration in vitro and causes tumor regression in vivo. Cancer Res 69(13):5441–5449. doi:10.1158/0008-5472.can-09-0302 CrossRefPubMedCentralPubMed

Titel: Lysophosphatidic acid induces anxiety-like behavior via its receptors in mice
verfasst von: Misa Yamada
Mai Tsukagoshi
Tomio Hashimoto
Jun-Ichiro Oka
Akiyoshi Saitoh
Mitsuhiko Yamada
Publikationsdatum: 01.03.2015
Verlag: Springer Vienna
Erschienen in: Journal of Neural Transmission / Ausgabe 3/2015
Print ISSN: 0300-9564
Elektronische ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-014-1289-9

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