RT Journal Article
T1 Chronic central modulation of LPA/LPA receptors-signaling pathway in the mouse brain regulates cognition, emotion, and hippocampal neurogenesis.
A1 Rosell-del-Valle, Cristina
A1 Pedraza-Benítez, María del Carmen
A1 Manuel, Iván
A1 Moreno-Rodríguez, Marta
A1 Rodríguez-Puertas, Rafael
A1 Castilla-Ortega, María Estela
A1 Caramés-Tejedor, José María
A1 Gómez-Conde, Ana Isabel
A1 Zambrana-Infantes, Emma
A1 Ortega-Pinazo, Jesús
A1 Serrano-Castro, Pedro Jesús
A1 Chun, Jerold
A1 Rodriguez-de-Fonseca, Fernando
A1 Santín-Núñez, Luis Javier
A1 Estivill-Torrús, Guillermo
K1 Hipocampo (Cerebro)
AB Several studies have demonstrated that lysophosphatidic acid (LPA) acts through its LPA receptors in multiple biological and behavioral processes, including adult hippocampal neurogenesis, hippocampal-dependent memory, and emotional regulation. However, analyses of the effects have typically involved acute treatments, and there is no information available regarding the effect of the chronic pharmacological modulation of the LPA/LPA receptors-signaling pathway. Thus, we analyzed the effect of the chronic (21 days) and continuous intracerebroventricular (ICV) infusion of C18:1 LPA and the LPA1-3 receptor antagonist Ki16425 in behavior and adult hippocampal neurogenesis. Twenty-one days after continuous ICV infusions, mouse behaviors in the open field test, Y-maze test and forced swimming test were assessed. In addition, the hippocampus was examined for c-Fos expression and α-CaMKII and phospho-α-CaMKII levels.The current study demonstrates that chronic C18:1 LPA produced antidepressant effects, improved spatial working memory, and enhanced adult hippocampal neurogenesis. In contrast, chronic LPA1-3 receptor antagonism disrupted exploratory activity and spatial working memory, induced anxiety and depression-like behaviors and produced an impairment of hippocampal neurogenesis. While these effects were accompanied by an increase in neuronal activation in the DG of C18:1 LPA-treated mice, Ki16425-treated mice showed reduced neuronal activation in CA3 and CA1 hippocampal subfields. Treatment with the antagonist also induced an imbalance in the expression of basal/activated α-CaMKII protein forms.These outcomes indicate that the chronic central modulation of the LPA receptors-signaling pathway in the brain regulates cognition and emotion, likely comprising hippocampal-dependent mechanisms. The use of pharmacological modulation of this pathway in the brain may potentially be targeted for the treatment of several neuropsychiatric conditions.
PB Progress in Neuro-Psychopharmacology and Biological Psychiatry
YR 2021
FD 2021-06-06
LK https://hdl.handle.net/10630/23857
UL https://hdl.handle.net/10630/23857
LA eng
NO This work was supported by grants from the Spanish Ministry of Science, Innovation and Universities, co-funded by the European Regional Development Fund (ERDF, EU), (PSI2017-82604R, to LJS; PSI2017-83408-P to CP; PI16/01510, to GET) and the Andalusian Regional Ministries of Economy, Knowledge, Business and University (CTS643 to GET) and of Health and Families (Nicolas Monardes Programme to GET). We gratefully acknowledge IBIMA joint support structures for research (ECAI) of Microscopy and Animal Experimentation for the immunohistology and maintenance of mice, respectively, as well as technical assistance. Technical and human support provided by the General Research Services SGIker [University of the Basque Country (UPV/EHU), Ministry of Science, Innovation and Universities, Basque Government, European Regional Development Fund (ERDF) and European Social Fund (ESF)] is gratefully acknowledged.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 23 ene 2026