3 results on '"Monica E. Ureña-Guerrero"'
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2. New Aspects of VEGF, GABA, and Glutamate Signaling in the Neocortex of Human Temporal Lobe Pharmacoresistant Epilepsy Revealed by RT-qPCR Arrays
- Author
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Monica E. Ureña-Guerrero, Luisa Rocha, Sandra Orozco-Suárez, Martha C. Rivera-Cervantes, Rubén Darío Castro-Torres, Carlos Beas-Zarate, Bárbara Estupiñán-Díaz, Lilia Morales-Chacón, Mario Alonso-Vanegas, and Lourdes Lorigados-Pedre
- Subjects
Adult ,Male ,Vascular Endothelial Growth Factor A ,0301 basic medicine ,Drug Resistant Epilepsy ,Adolescent ,MAP Kinase Signaling System ,Racemases and Epimerases ,Glutamic Acid ,Neocortex ,Biology ,Phosphatidylinositol 3-Kinases ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Epilepsy ,0302 clinical medicine ,Receptors, GABA ,Gene expression ,medicine ,Humans ,Temporal cortex ,Gephyrin ,Glutamate receptor ,Membrane Proteins ,General Medicine ,Middle Aged ,medicine.disease ,Vascular endothelial growth factor ,030104 developmental biology ,Epilepsy, Temporal Lobe ,chemistry ,Serine racemase ,biology.protein ,Cancer research ,STAT protein ,Female ,Transcriptome ,030217 neurology & neurosurgery - Abstract
In the epilepsy spectrum, temporal lobe epilepsy (TLE) is the most common and devastating focal and symptomatic epilepsy form in adults, where more than 30% of patients develop pharmacoresistance. It is not fully understood how the gene expression contributes to establishing an epileptic phenotype. Cerebrovascular remodeling directed by VEGF (vascular endothelial growth factor) signaling might modulate the synaptic neurotransmission in the epileptic brain. To address this question, the gene expression was profiled in biopsies of the temporal cortex from diagnosed patients with pharmacoresistant TLE that underwent surgical resection to seizure control. One hundred sixty-eight genes related to VEGF signaling and GABA and glutamate neurotransmissions were evaluated. Genes related to downstream signaling -phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinases (MAPK), and Janus-activated kinase/signal transducer and activator of transcription (JAK/STAT) pathways- and neurotransmitters metabolism were evaluated too. Thirty-nine genes were upregulated. The genes encoding for G protein q polypeptide, serine racemase, gephyrin, and glutamate/cystine antiporter system xCT appeared as novel upregulated genes in the pharmacoresistant TLE. ClueGO, a Cytoscape plugin, was used to build a gene network associated using Gene Ontology (GO) terminology. Enrichment analysis by ClueGO retrieves that positive regulation of endothelial cell proliferation, nerve development, and neuronal apoptosis were over-represented categories. In conclusion, VEGF signaling is confirmed as a relevant mediator in the pharmacoresistant TLE. In addition, the enrichment analysis applied to differentially expressed genes suggests new pharmacological targets to be assessed in the treatment of pharmacoresistant TLE. Results make up an approximation to better understand the epileptic brain and complement the available data.
- Published
- 2020
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3. KB-R7943 reduces 4-aminopyridine-induced epileptiform activity in adult rats after neuronal damage induced by neonatal monosodium glutamate treatment
- Author
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Monica E. Ureña-Guerrero, Mariana Hernandez-Ojeda, Carlos Beas-Zarate, Jazmin A. Cardenas-Castillo, Paola E. Gutierrez-Barajas, and Antoni Camins
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Male ,0301 basic medicine ,Monosodium glutamate ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Excitotoxicity ,Gene Expression ,lcsh:Medicine ,Hippocampus ,medicine.disease_cause ,Epileptogenesis ,Epilepsy ,chemistry.chemical_compound ,0302 clinical medicine ,Sodium Glutamate ,Pharmacology (medical) ,4-Aminopyridine ,Chemistry ,Thiourea ,KB-R7943 ,General Medicine ,Infusions, Intraventricular ,Anesthesia ,Anticonvulsants ,medicine.drug ,medicine.medical_specialty ,03 medical and health sciences ,Seizures ,Internal medicine ,medicine ,Animals ,Rats, Wistar ,Molecular Biology ,Entorhinal cortex ,Homeodomain Proteins ,Research ,lcsh:R ,Biochemistry (medical) ,Cell Biology ,medicine.disease ,Rats ,030104 developmental biology ,Endocrinology ,NCX1-3 ,030217 neurology & neurosurgery ,Homeostasis - Abstract
Background Neonatal monosodium glutamate (MSG) treatment triggers excitotoxicity and induces a degenerative process that affects several brain regions in a way that could lead to epileptogenesis. Na+/Ca2+ exchangers (NCX1-3) are implicated in Ca2+ brain homeostasis; normally, they extrude Ca2+ to control cell inflammation, but after damage and in epilepsy, they introduce Ca2+ by acting in the reverse mode, amplifying the damage. Changes in NCX3 expression in the hippocampus have been reported immediately after neonatal MSG treatment. In this study, the expression level of NCX1-3 in the entorhinal cortex (EC) and hippocampus (Hp); and the effects of blockade of NCXs on the seizures induced by 4-Aminopyridine (4-AP) were analysed in adult rats after neonatal MSG treatment. KB-R7943 was applied as NCXs blocker, but is more selective to NCX3 in reverse mode. Methods Neonatal MSG treatment was applied to newborn male rats at postnatal days (PD) 1, 3, 5, and 7 (4 g/kg of body weight, s.c.). Western blot analysis was performed on total protein extracts from the EC and Hp to estimate the expression level of NCX1-3 proteins in relative way to the expression of β-actin, as constitutive protein. Electrographic activity of the EC and Hp were acquired before and after intracerebroventricular (i.c.v.) infusion of 4-AP (3 nmol) and KB-R7943 (62.5 pmol), alone or in combination. All experiments were performed at PD60. Behavioural alterations were also recorder. Results Neonatal MSG treatment significantly increased the expression of NCX3 protein in both studied regions, and NCX1 protein only in the EC. The 4-AP-induced epileptiform activity was significantly higher in MSG-treated rats than in controls, and KB-R7943 co-administered with 4-AP reduced the epileptiform activity in more prominent way in MSG-treated rats than in controls. Conclusions The long-term effects of neonatal MSG treatment include increases on functional expression of NCXs (mainly of NCX3) in the EC and Hp, which seems to contribute to improve the control that KB-R7943 exerted on the seizures induced by 4-AP in adulthood. The results obtained here suggest that the blockade of NCXs could improve seizure control after an excitotoxic process; however, this must be better studied. Electronic supplementary material The online version of this article (doi:10.1186/s12929-017-0335-y) contains supplementary material, which is available to authorized users.
- Published
- 2017
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