1. Department of Pharmacology, Faculty of Medicine and Odontology, University of the Basque Country, UPV/EHU, Leioa, Spain;2. Molecular and Cellular Neuroscience Department, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California, USA;3. UGC Intercentros de Neurociencias y UGC de Salud Mental, Instituto de Investigación Biomédica de Malaga (IBIMA), Hospitales Universitarios Regional de Málaga y Virgen de la Victoria, Universidad de Málaga, Spain;4. Departmento de Psicobiología y Metodología de las Ciencias del Comportamiento. Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad of Málaga, Málaga, Spain;5. Institute of Neuropathology, University Hospital Bellvitge, University of Barcelona, Ciberned, Spain
Abstract:
Lysophosphatidic acid (LPA) is a signaling molecule that binds to six known G protein‐coupled receptors: LPA1–LPA6. LPA evokes several responses in the CNS, including cortical development and folding, growth of the axonal cone and its retraction process. Those cell processes involve survival, migration, adhesion proliferation, differentiation, and myelination. The anatomical localization of LPA1 is incompletely understood, particularly with regard to LPA binding. Therefore, we have used functional 35S]GTPγS autoradiography to verify the anatomical distribution of LPA1 binding sites in adult rodent and human brain. The greatest activity was observed in myelinated areas of the white matter such as corpus callosum, internal capsule and cerebellum. MaLPA1‐null mice (a variant of LPA1‐null) lack 35S]GTPγS basal binding in white matter areas, where the LPA1 receptor is expressed at high levels, suggesting a relevant role of the activity of this receptor in the most myelinated brain areas. In addition, phospholipid precursors of LPA were localized by MALDI‐IMS in both rodent and human brain slices identifying numerous species of phosphatides and phosphatidylcholines. Both phosphatides and phosphatidylcholines species represent potential LPA precursors. The anatomical distribution of these precursors in rodent and human brain may indicate a metabolic relationship between LPA and LPA1 receptors.
