RT Journal Article
T1 Loss of lysophosphatidic acid receptor LPA1 alters oligodendrocyte differentiation and myelination in the mouse cerebral cortex
A1 Garcia Diaz, Beatriz
A1 Riquelme, Raquel
A1 Varela Nieto, Isabel
A1 Jiménez-Lara, Antonio Jesús
A1 De-Diego-Barbado, Isabel
A1 Gómez-Conde, Ana Isabel
A1 Matas-Rico, Elisa
A1 Aguirre-Gómez, José Ángel
A1 Chun, Jerold
A1 Pedraza-Benítez, María del Carmen
A1 Santín-Núñez, Luis Javier
A1 Fernández Fernández, Óscar
A1 Rodriguez-de-Fonseca, Fernando
A1 Estivill-Torrús, Guillermo
K1 Corteza cerebral
AB Lysophosphatidic acid (LPA) is an intercellular signaling lipid that regulates multiple cellular functions, acting through specific G-protein coupled receptors (LPA1–6). Our previous studies using viable Malaga variant maLPA1-null mice demonstrated the requirement of the LPA1 receptor for normal proliferation, differentiation, and survival of the neuronal precursors. In the cerebral cortex LPA1 is expressed extensively in differentiating oligodendrocytes, in parallel with myelination. Although exogenous LPA-induced effects have been investigated in myelinating cells, the in vivo contribution of LPA1 to normal myelination remains to be demonstrated. This study identified a relevant in vivo role for LPA1 as a regulator of cortical myelination. Immunochemical analysis in adult maLPA1-null mice demonstrated a reduction in the steady-state levels of the myelin proteins MBP, PLP/DM20, and CNPase in the cerebral cortex. The myelin defects were confirmed using magnetic resonance spectroscopy and electron microscopy. Stereological analysis limited the defects to adult differentiating oligodendrocytes, without variation in the NG2+ precursor cells. Finally, a possible mechanism involving oligodendrocyte survival was demonstrated by the impaired intracellular transport of the PLP/DM20 myelin protein which was accompanied by cellular loss, suggesting stress-induced apoptosis. These findings describe a previously uncharacterized in vivo functional role for LPA1 in the regulation of oligodendrocyte differentiation and myelination in the CNS, underlining the importance of the maLPA1-null mouse as a model for the study of demyelinating diseases.
PB Springer Link
YR 2014
FD 2014
LK https://hdl.handle.net/10630/32328
UL https://hdl.handle.net/10630/32328
LA eng
NO García-Díaz, B., Riquelme, R., Varela-Nieto, I. et al. Loss of lysophosphatidic acid receptor LPA1 alters oligodendrocyte differentiation and myelination in the mouse cerebral cortex. Brain Struct Funct 220, 3701–3720 (2015). https://doi.org/10.1007/s00429-014-0885-7
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026