RT Journal Article
T1 maLPA1-null mice as an endophenotype of anxious depression
A1 Moreno-Fernández, R D
A1 Pérez-Martín, M
A1 Castilla-Ortega, E
A1 Rosell Del Valle, C
A1 García-Fernández, M I
A1 Chun, J
A1 Estivill-Torrús, G
A1 Rodríguez de Fonseca, F
A1 Santín, L J
A1 Pedraza, C
K1 Animales
K1 Antidepresivos
K1 Ansiedad
K1 Encéfalo
K1 Depresión
K1 Endofenotipos
K1 Genotipo
K1 Humanos
K1 Lisofosfolípidos
K1 Ratones
K1 Ratones noqueados
K1 Modelos animales
K1 Trastornos del humor
K1 Pánico
K1 Pronóstico
K1 Receptores del ácido lisofosfatídico
AB 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.
PB Nature Publishing Group
YR 2017
FD 2017-04-04
LK http://hdl.handle.net/10668/2670
UL http://hdl.handle.net/10668/2670
LA en
NO 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.
DS RISalud
RD Apr 20, 2025