Please use this identifier to cite or link to this item: http://hdl.handle.net/10668/2670
Título : maLPA1-null mice as an endophenotype of anxious depression
Autor : Moreno-Fernández, R D
Pérez-Martín, M
Castilla-Ortega, E
Rosell Del Valle, C
García-Fernández, M I
Chun, J
Estivill-Torrús, G
Rodríguez de Fonseca, F
Santín, L J
Pedraza, C
Filiación: [Moreno-Fernández ,RD; Rosell del Valle,C; Santín,LJ; Pedraza,C] Departamento de Psicobiología y Metodología de las CC, Facultad de Psicología, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain. [Pérez-Martín,M] Departamento de Biología Celular, Genética y Fisiología, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain. [Castilla-Ortega,E; Rodríguez de Fonseca,F] Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Málaga, Spain. [García-Fernández,MI] Departamento de Fisiología y Medicina Deportiva, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain. [Chun,J] Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA. [Estivill-Torrús,G] Unidad de Gestión Clínica de Neurociencias, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitarios de Málaga, Málaga, Spain.
Palabras clave : Animales
Antidepresivos
Ansiedad
Encéfalo
Depresión
Endofenotipos
Genotipo
Humanos
Lisofosfolípidos
Ratones
Ratones noqueados
Modelos animales
Trastornos del humor
Pánico
Pronóstico
Receptores del ácido lisofosfatídico
MeSH: Medical Subject Headings::Psychiatry and Psychology::Behavior and Behavior Mechanisms::Neurobehavioral Manifestations::Anhedonia
Medical Subject Headings::Organisms::Eukaryota::Animals
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Central Nervous System Agents::Psychotropic Drugs::Antidepressive Agents
Medical Subject Headings::Psychiatry and Psychology::Behavior and Behavior Mechanisms::Emotions::Anxiety
Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain
Medical Subject Headings::Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Behavioral Symptoms::Depression
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Phenotype::Endophenotypes
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genotype
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Chemicals and Drugs::Lipids::Membrane Lipids::Phospholipids::Glycerophosphates::Phosphatidic Acids::Lysophospholipids
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice
Medical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Genetically Modified::Mice, Transgenic::Mice, Knockout
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Animal
Medical Subject Headings::Psychiatry and Psychology::Mental Disorders::Mood Disorders
Medical Subject Headings::Psychiatry and Psychology::Behavior and Behavior Mechanisms::Emotions::Fear::Panic
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, G-Protein-Coupled::Receptors, Lysophospholipid::Receptors, Lysophosphatidic Acid
Fecha de publicación : 4-Apr-2017
Editorial : Nature Publishing Group
Cita Bibliográfica: Moreno-Fernández RD, Pérez-Martín M, Castilla-Ortega E, Rosell del Valle C, García-Fernández MI, Chun J, et al. maLPA1-null mice as an endophenotype of anxious depression. Transl Psychiatry. 2017;7(4):e1077.
Abstract: Anxious depression is a prevalent disease with devastating consequences and a poor prognosis. Nevertheless, the neurobiological mechanisms underlying this mood disorder remain poorly characterized. The LPA1 receptor is one of the six characterized G protein-coupled receptors (LPA1-6) through which lysophosphatidic acid acts as an intracellular signalling molecule. The loss of this receptor induces anxiety and several behavioural and neurobiological changes that have been strongly associated with depression. In this study, we sought to investigate the involvement of the LPA1 receptor in mood. We first examined hedonic and despair-like behaviours in wild-type and maLPA1 receptor null mice. Owing to the behavioural response exhibited by the maLPA1-null mice, the panic-like reaction was assessed. In addition, c-Fos expression was evaluated as a measure of the functional activity, followed by interregional correlation matrices to establish the brain map of functional activation. maLPA1-null mice exhibited anhedonia, agitation and increased stress reactivity, behaviours that are strongly associated with the psychopathological endophenotype of depression with anxiety features. Furthermore, the functional brain maps differed between the genotypes. The maLPA1-null mice showed increased limbic-system activation, similar to that observed in depressive patients. Antidepressant treatment induced behavioural improvements and functional brain normalisation. Finally, based on validity criteria, maLPA1-null mice are proposed as an animal model of anxious depression. Here, for we believe the first time, we have identified a possible relationship between the LPA1 receptor and anxious depression, shedding light on the unknown neurobiological basis of this subtype of depression and providing an opportunity to explore new therapeutic targets for the treatment of mood disorders, especially for the anxious subtype of depression.
URI: http://hdl.handle.net/10668/2670
Versión del editor : http://www.nature.com/tp/journal/v7/n4/abs/tp201724a.html
DOI: 10.1038/tp.2017.24
ISSN : 2158-3188 (Online)
Appears in Collections:01- Artículos - IBIMA. Instituto de Investigación Biomédica de Málaga
01- Artículos - Hospital Regional de Málaga

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