Attenuation of cocaine-induced conditioned locomotion is associated with altered expression of hippocampal glutamate receptors in mice lacking LPA1 receptors

Blanco, Eduardo; Bilbao, Ainhoa; Rojas, María Jesús Luque; Palomino, A.; Bermúdez‐Silva, Francisco Javier; Suárez, Juan; Santín, Luis J.; Estivill‐Torrús, Guillermo; Gutiérrez, Antonia; Campos-Sandoval, José A.; Alonso-Carrion, Francisco Jose; Márquez, Javier; Fonseca, Fernando Rodrı́guez de

doi:10.1007/s00213-011-2446-6

Cited by 42 publications

(41 citation statements)

References 44 publications

(49 reference statements)

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“…The maLPA 1 -null mouse, or ''Malaga variant'' , is a stable variant of the original LPA 1 -null mutant (Contos et al 2000) that carries the deletion of exon 3, which contains the transmembrane domains I-VI of the receptor. This variant exhibits more pronounced defects than the original mutant, due most likely to the interaction of the Lpar1 gene with as yet unknown genetic modifiers , and including defects affecting the development of cortical precursors , adult hippocampal neurogenesis , and motor, emotional, and cognitive alterations involving long-term spatial, contextual, and episodic-like memory (Santín et al 2009;Castilla-Ortega et al 2010, 2011Blanco et al 2012;García-Fernández et al 2012;Estivill-Torrús et al 2013;Pedraza et al 2014).…”

Section: Introductionmentioning

confidence: 94%

Loss of lysophosphatidic acid receptor LPA1 alters oligodendrocyte differentiation and myelination in the mouse cerebral cortex

et al. 2014

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Lysophosphatidic acid (LPA) is an intercellular signaling lipid that regulates multiple cellular functions, acting through specific G-protein coupled receptors (LPA(1-6)). 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.

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Section: Introductionmentioning

confidence: 94%

Loss of lysophosphatidic acid receptor LPA1 alters oligodendrocyte differentiation and myelination in the mouse cerebral cortex

et al. 2014

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“…Subunits of AMPAR were counted only in TH-positive dendrites. The TH and GluA3 antibodies have been cited in previous studies (He et al, 1998;Blanco et al, 2012). Antibodies against AMPAR subunits were selected because they were affinity-purified and the specificity was confirmed with western blot and by negative binding on tissue sections when the antibody was previously exposed to antigen peptide.…”

Section: Cell Identificationmentioning

confidence: 99%

Excitatory Synaptic Function and Plasticity is Persistently Altered in Ventral Tegmental Area Dopamine Neurons after Prenatal Ethanol Exposure

Hausknecht

Haj‐Dahmane

Shen

et al. 2014

Neuropsychopharmacol

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Prenatal ethanol exposure (PE) is one of the developmental factors leading to increased addiction propensity (risk). However, the neuronal mechanisms underlying this effect remain unknown. We examined whether increased excitatory synaptic transmission in ventral tegmental area (VTA) dopamine (DA) neurons, which is associated with drug addiction, was impacted by PE. Pregnant rats were exposed to ethanol (0 or 6 g/kg/day) via intragastric intubation from gestational day 8-20. Amphetamine self-administration, whole-cell recordings, and electron microscopy were performed in male offspring between 2 and 12-week-old. The results showed enhanced amphetamine selfadministration in PE animals. In PE animals, we observed a persistent augmentation in calcium-permeable AMPA receptor (CP-AMPAR) expression, indicated by increased rectification and reduced decay time of AMPAR-mediated excitatory postsynaptic currents (AMPAREPSCs), enhanced depression of AMPAR-EPSCs by NASPM (a selective CP-AMPAR antagonist), and increased GluA3 subunits in VTA DA neuron dendrites. Increased CP-AMPAR expression in PE animals led to enhanced excitatory synaptic strength and the induction of CP-AMPAR-dependent long-term potentiation (LTP), an anti-Hebbian form of LTP. These observations suggest that, in PE animals, increased excitatory synaptic strength in VTA DA neurons might be susceptible to further strengthening even in the absence of impulse flow. The PE-induced persistent increase in CP-AMPAR expression, the resulting enhancement in excitatory synaptic strength, and CP-AMPAR-dependent LTP are similar to effects observed after repeated exposure to drugs of abuse, conditions known to increase addiction risk. Therefore, these mechanisms could be important neuronal substrates underlying PE-induced enhancement in amphetamine selfadministration and increased addiction risk in individuals with fetal alcohol spectrum disorders.

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“…Experiments were performed in duplicates with a Lightcycler2.0 instrument (Roche Diagnostics, Mannheim, Germany) under the following PCR conditions: initial denaturation at 95 1C for 10 min, followed by 40 cycles of denaturation (95 1C for 10 s), and a combined annealing and extension phase (60 1C for 30 s). The primers used were as follows: synapsin I (fwd: 5 0 -CACCGACTGGGCAAAATACT-3 0 ; rev: 5 0 -TCCGAAGAAC-TTCCATGTCC-3 0 ); synapsin II (fwd: 5 0 -CCTTCATC-GACGCCAAGTAT-3 0 ; rev: 5 0 -GAGCAGGCATCTACCCAG-AG-3 0 ); Glt-1 (Perisic et al, 2010); GluR1 and GluR2 (Blanco et al, 2011); and GAPDH (fwd: 5 0 -CCATCACCATCTTC-CAGGAGCGAG-3 0 ; rev: 5 0 -GATGGCATGGACTGTGGTCAT-GAG-3 0 ). Relative gene expression was determined by the 2 ÀDDC T method (Livak and Schmittgen, 2001).…”

Section: Real-time Pcrmentioning

confidence: 99%

Intranasally Administered Neuropeptide S (NPS) Exerts Anxiolytic Effects Following Internalization Into NPS Receptor-Expressing Neurons

Ionescu

Dine

Yen

et al. 2012

Neuropsychopharmacol

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Experiments in rodents revealed neuropeptide S (NPS) to constitute a potential novel treatment option for anxiety diseases such as panic and post-traumatic stress disorder. However, both its cerebral target sites and the molecular underpinnings of NPS-mediated effects still remain elusive. By administration of fluorophore-conjugated NPS, we pinpointed NPS target neurons in distinct regions throughout the entire brain. We demonstrated their functional relevance in the hippocampus. In the CA1 region, NPS modulates synaptic transmission and plasticity. NPS is taken up into NPS receptor-expressing neurons by internalization of the receptor-ligand complex as we confirmed by subsequent cell culture studies. Furthermore, we tracked internalization of intranasally applied NPS at the single-neuron level and additionally demonstrate that it is delivered into the mouse brain without losing its anxiolytic properties. Finally, we show that NPS differentially modulates the expression of proteins of the glutamatergic system involved inter alia in synaptic plasticity. These results not only enlighten the path of NPS in the brain, but also establish a non-invasive method for NPS administration in mice, thus strongly encouraging translation into a novel therapeutic approach for pathological anxiety in humans.

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Attenuation of cocaine-induced conditioned locomotion is associated with altered expression of hippocampal glutamate receptors in mice lacking LPA1 receptors

Cited by 42 publications

References 44 publications

Loss of lysophosphatidic acid receptor LPA1 alters oligodendrocyte differentiation and myelination in the mouse cerebral cortex

Loss of lysophosphatidic acid receptor LPA1 alters oligodendrocyte differentiation and myelination in the mouse cerebral cortex

Excitatory Synaptic Function and Plasticity is Persistently Altered in Ventral Tegmental Area Dopamine Neurons after Prenatal Ethanol Exposure

Intranasally Administered Neuropeptide S (NPS) Exerts Anxiolytic Effects Following Internalization Into NPS Receptor-Expressing Neurons

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