RT Journal Article
T1 Glutaminase and MMP-9 Downregulation in Cortex and Hippocampus of LPA1 Receptor Null Mice Correlate with Altered Dendritic Spine Plasticity.
A1 Peñalver, Ana
A1 Campos-Sandoval, Jose A
A1 Blanco, Eduardo
A1 Cardona, Carolina
A1 Castilla, Laura
A1 Martin-Rufian, Mercedes
A1 Estivill-Torrus, Guillermo
A1 Sanchez-Varo, Raquel
A1 Alonso, Francisco J
A1 Perez-Hernandez, Mercedes
A1 Colado, Maria I
A1 Gutierrez, Antonia
A1 Rodriguez-de-Fonseca, Fernando
A1 Marquez, Javier
K1 Glutamate
K1 Glutaminase
K1 Lysophosphatidic acid
K1 Matrix metalloproteinases
K1 Rodent knockout model
K1 Synaptic plasticity
AB Lysophosphatidic acid (LPA) is an extracellular lipid mediator that regulates nervous system development and functions acting through G protein-coupled receptors (GPCRs). Here we explore the crosstalk between LPA1 receptor and glutamatergic transmission by examining expression of glutaminase (GA) isoforms in different brain areas isolated from wild-type (WT) and KOLPA1 mice. Silencing of LPA1 receptor induced a severe down-regulation of Gls-encoded long glutaminase protein variant (KGA) (glutaminase gene encoding the kidney-type isoforms, GLS) protein expression in several brain regions, particularly in brain cortex and hippocampus. Immunohistochemical assessment of protein levels for the second type of glutaminase (GA) isoform, glutaminase gene encoding the liver-type isoforms (GLS2), did not detect substantial differences with regard to WT animals. The regional mRNA levels of GLS were determined by real time RT-PCR and did not show significant variations, except for prefrontal and motor cortex values which clearly diminished in KO mice. Total GA activity was also significantly reduced in prefrontal and motor cortex, but remained essentially unchanged in the hippocampus and rest of brain regions examined, suggesting activation of genetic compensatory mechanisms and/or post-translational modifications to compensate for KGA protein deficit. Remarkably, Golgi staining of hippocampal regions showed an altered morphology of glutamatergic pyramidal cells dendritic spines towards a less mature filopodia-like phenotype, as compared with WT littermates. This structural change correlated with a strong decrease of active matrix-metalloproteinase (MMP) 9 in cerebral cortex and hippocampus of KOLPA1 mice. Taken together, these results demonstrate that LPA signaling through LPA1 influence expression of the main isoenzyme of glutamate biosynthesis with strong repercussions on dendritic spines maturation, which may partially explain the cognitive and learning defects previously reported for this colony of KOLPA1 mice.
PB Frontiers Research Foundation
SN 1662-5099
YR 2017
FD 2017-09-05
LK http://hdl.handle.net/10668/11593
UL http://hdl.handle.net/10668/11593
LA en
NO Peñalver A, Campos-Sandoval JA, Blanco E, Cardona C, Castilla L, Martín-Rufián M, et al. Glutaminase and MMP-9 Downregulation in Cortex and Hippocampus of LPA1 Receptor Null Mice Correlate with Altered Dendritic Spine Plasticity. Front Mol Neurosci. 2017 Sep 5;10:278
DS RISalud
RD Apr 12, 2025