Original Research ARTICLE
Effects of the LPA1 receptor deficiency and stress on the hippocampal LPA species in mice.
- 1Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Facultad de Psicología, Universidad de Málaga, Spain
- 2Biomedical Research Institute of Malaga, University of Málaga, Spain
- 3Sanford Burnham Prebys Medical Discovery Institute, United States
- 4Department of Physiology and Sports Medicine, University of Málaga, Spain
- 5Clinical Management Unit of Neurosciences, University Regional Hospital of Malaga, Spain
- 6Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario de Malaga, Spain
- 7Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Portugal
- 8Departamento Biología Celular, Genética y Fisiología, Universidad de Málaga, Spain
Lysophosphatidic acid (LPA) is an important bioactive lipid species that functions in intracellular signaling through six characterized G protein-coupled receptors (LPA1–6). Among these receptors, LPA1 is a strong candidate to mediate the central effects of LPA on emotion and may be involved in promoting normal emotional behaviors. Alterations in this receptor may induce vulnerability to stress and predispose an individual to a psychopathological disease. In fact, mice lacking the LPA1 receptor exhibit emotional dysregulation and cognitive alterations in hippocampus-dependent tasks. Moreover, the loss of this receptor results in a phenotype of low resilience with dysfunctional coping in response to stress and induces anxiety and several behavioral and neurobiological changes that are strongly correlated with mood disorders. In fact, our group proposes that maLPA1-null mice represent an animal model of anxious depression.
However, despite the key role of the LPA-LPA1-pathway in emotion and stress coping behaviors, the available information describing the mechanisms by which the LPA-LPA1-pathway regulates emotion is currently insufficient. Because activation of LPA1 requires LPA, here, we used a Matrix-Assisted Laser Desorption/ Ionization mass spectrometry-based approach to evaluate the effects of an LPA1 receptor deficiency on the hippocampal levels of LPA species. Additionally, the impact of stress on the LPA profile was also examined in both wild-type (WT) and the Malaga variant of LPA1-null mice (maLPA1-null-mice). Mice lacking LPA1 did not exhibit gross perturbations in the hippocampal LPA species, but the LPA profile was modified, showing an altered relative abundance of 18:0 LPA. Regardless of the genotype, restraint stress produced profound changes in all LPA species examined, revealing that hippocampal LPA species are a key target of stress. Finally, the relationship between the hippocampal levels of LPA species and performance in the elevated plus maze was established.
To our knowledge, this study is the first to detect, identify and profile LPA species in the hippocampus of both LPA1-receptor null mice and WT mice at baseline and after acute stress, as well as to link these LPA species with anxiety-like behaviors. In conclusion, the hippocampal LPA species are a key target of stress and may be involved in psychopathological conditions.
Keywords: LPA1 receptor, LPA species, MALDI-TOFF mass spectrometry , stress, Emotions
Received: 21 Dec 2018;
Accepted: 17 May 2019.
Edited by:Michael J. Schmeisser, University Medical Centre, Johannes Gutenberg University Mainz, Germany
Reviewed by:Markus Wöhr, University of Marburg, Germany
Thomas Roskoden, Institute of Anatomy, Faculty of Medicine, University Hospital Magdeburg, Germany
Copyright: © 2019 Tabbai, Moreno-Fernández, Zambrana-Infantes, Nieto-Quero, Chun, Garcia-Fernandez, Estivill-Torrús, RODRIGUEZ DE FONSECA, Santín, Oliveira, Perez-Martin and Pedraza. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Dr. Margarita Perez-Martin, Departamento Biología Celular, Genética y Fisiología, Universidad de Málaga, Malaga, 29071, Spain, firstname.lastname@example.org
Prof. Carmen Pedraza, Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Facultad de Psicología, Universidad de Málaga, Málaga, 29071, Andalusia, Spain, email@example.com