Laboratorio Of Medicina Regenerativa

Málaga, Spain

Laboratorio Of Medicina Regenerativa

Málaga, Spain
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Suarez J.,Laboratorio Of Medicina Regenerativa | Romero-Zerbo S.Y.,Laboratorio Of Medicina Regenerativa | Rivera P.,Laboratorio Of Medicina Regenerativa | Bermudez-Silva F.J.,Laboratorio Of Medicina Regenerativa | And 3 more authors.
Journal of Comparative Neurology | Year: 2010

Endocannabinoids (ECs) are important neuromodulators involved in a plethora of physiological processes such as modulation of synaptic transmission, neuroprotection, immune function, and neurodevelopment, among others. However, still lacking is a detailed study on the presence of this system in the circumventricular areas, brain structures controlling the interaction between cerebrospinal fluid and brain parenchyma. The aim of this work was to provide the anatomical basis supporting a functional role of ECs in the activity of circumventricular areas. To this end, an immunohistochemical study of the EC system in rat brain was performed. Receptors and synthesizing and degrading enzymes for ECs were widely distributed in rat ependyma and subependyma, marginal glia, and circumventricular organs (CVOs) such as the choroid plexus, subfornical organ, subcommissural organ, median eminence, and area postrema. These zones constitute barrier systems between the brain parenchyma and the ventricular or subarachnoid cerebrospinal fluid (CSF) and between the extracellular hemal milieu of CVOs and the brain parenchyma or the CSF. By immunohistochemistry and real-time polymerase chain reaction we found DAGLα, DAGLβ, NAPE-PLD, MAGL, and FAAH in the ependyma. These finding suggest that the ependyma can release and clear ECs from the ventricular CSF. Subependymal astrocytes and tanycytes displayed DAGLa immunoreactivity but parenchymal astrocytes did not express EC-synthesizing enzymes, thus establishing a sharp distinction between these two astrocyte populations. CB1 was located in fibers innervating discrete subventricular zones such as the neurogenic striatal subventricular zone and the fourth ventricle. CB1 fibers also innervated some CVOs. © 2010 Wiley-Liss, Inc.


Plaza-Zabala A.,University Pompeu Fabra | Berrendero F.,University Pompeu Fabra | Suarez J.,Laboratorio Of Medicina Regenerativa | Bermudez-Silva F.J.,Laboratorio Of Medicina Regenerativa | And 8 more authors.
Synapse | Year: 2010

MDMA (3,4-Methylenedioxymethamphetamine) is an amphetamine derivative widely used for recreational purposes. We have recently shown that repeated treatment with high doses of MDMA-induced impairments in the acquisition and recall of an active avoidance task in mice. In this study, we examined whether the endogenous peroxisome proliferator-activated receptor-α (PPAR-α) agonist, oleoylethanolamide (OEA) protects against these MDMA-induced deficits. Mice were pretreated twice a day with OEA (0, 5, and 25 mg/kg) 30 min before an injection of MDMA (30 mg/kg) or saline during four consecutive days. Twenty-four hours after the last treatment, animals were trained in an active avoidance task for two consecutive weeks. After a 5-day resting period, a recall session was performed. Mice treated with MDMA showed reduced learning and recall of the task when compared with saline-treated controls. OEA at 5 mg/kg ameliorated and at 25 mg/kg worsened this deficit. Dopamine transporter (DAT)-binding sites significantly decreased 4 days after the last MDMA administration and pretreatment with both doses of OEA prevented this effect. In immunohistochemical studies, coexpression of tyrosine-hydroxylase and PPAR-α receptors was observed in the striatum and substantia nigra pars compacta of mice. These results suggest that OEA administration can modulate the cognitive deficits induced by MDMA in a DAT-independent manner. © 2009 Wiley-Liss, Inc.


Bermudez-Silva F.J.,Laboratorio Of Medicina Regenerativa | Perez J.,University of Malaga | Cifuentes M.,University of Malaga | Perez-Martin M.,University of Malaga | And 4 more authors.
Journal of Neuroscience Methods | Year: 2010

The subcommissural organ (SCO) releases into the cerebrospinal fluid (CSF) large glycoproteins that polymerize forming the Reissner's fibre (RF), which is involved in CSF circulation and homeostasis. We obtained high purity primary cultures of bovine secretory SCO cells and measured glycoprotein release by a reliable and sensitive ELISA method. We also analysed the effect of regulatory ligands known to control the secretory activity of the SCO. Cells cultured for short time (4 h) released a high amount of glycoproteins that decreased with time. In young cultures, ATP increased and serotonin inhibited secretion rate. By contrast the acetylcholine agonist carbachol and high potassium did not evoke any detectable change in SCO glycoprotein release. These results support not only the suitability of the methodological approach but an important role of both ATP and serotonin in regulating SCO secretory activity as well. © 2010 Elsevier B.V.


Lopez Rodriguez A.B.,Complutense University of Madrid | Mateos Vicente B.,Complutense University of Madrid | Romero-Zerbo S.Y.,Laboratorio Of Medicina Regenerativa | Rodriguez-Rodriguez N.,Complutense University of Madrid | And 6 more authors.
Cerebral Cortex | Year: 2011

The neuroactive steroid estradiol reduces reactive astroglia after brain injury by mechanisms similar to those involved in the regulation of reactive gliosis by endocannabinoids. In this study, we have explored whether cannabinoid receptors are involved in the effects of estradiol on reactive astroglia. To test this hypothesis, the effects of estradiol, the cannabinoid CB1 antagonist/inverse agonist AM251, and the cannabinoid CB2 antagonist/inverse agonist AM630 were assessed in the cerebral cortex of male rats after a stab wound brain injury. Estradiol reduced the number of vimentin immunoreactive astrocytes and the number of glial fibrillary acidic protein immunoreactive astrocytes in the proximity of the wound. The effect of estradiol was significantly inhibited by the administration of either CB1 or CB2 receptor antagonists. The effect of estradiol may be in part mediated by alterations in endocannabinoid signaling because the hormone increased in the injured cerebral cortex the messenger RNA levels of CB2 receptors and of some of the enzymes involved in the synthesis and metabolism of endocannabinoids. These findings suggest that estradiol may decrease reactive astroglia in the injured brain by regulating the activity of the endocannabinoid system. © 2011 The Author.


Vida M.,Laboratorio Of Medicina Regenerativa | Serrano A.,Laboratorio Of Medicina Regenerativa | Serrano A.,CIBER ISCIII | Romero-Cuevas M.,Laboratorio Of Medicina Regenerativa | And 13 more authors.
Liver International | Year: 2013

Background: LFABP plays a critical role in the uptake and intracellular transport of fatty acids (FA) and other peroxisome proliferator-activated receptor alpha (PPARα) ligands. PPARα activation by PPARα ligands bound to LFABP results in gene expression of FA oxidation enzymes and de novo LFABP. The cytokine IL-6 is involved in regulating liver lipid oxidation. Aims: To study the ability of IL-6 to modulate the expression of the LFABP in hepatocytes. Methods: HepG2 and mouse primary hepatocytes were used to test LFABP mRNA and protein expression after IL-6 and PPARα-ligand treatments. Mice lacking IL-6 and wild-type C57Bl/6 were subjected to a fasting/re-feeding cycle to monitor hepatic LFABP mRNA kinetics after food intake. Results: In hepatocyte cultures, IL-6 treatment stimulated a LFABP mRNA sustained expression. Combined treatment of IL-6 plus PPARα ligands further enhanced LFABP gene and protein expression. In contrast, pretreatment with the PPARα-antagonist GW-6471 prevented the up-regulation of LFABP mRNA induced by IL-6 in the late phase of LFABP kinetics. Furthermore, the up-regulation of LFABP mRNA observed in the liver of wild-type mice 8 h after re-feeding was absent in mice lacking IL-6. Conclusions: IL-6 induces LFABP kinetics in hepatocytes and is partially dependent on PPARα. The maximum increase in LFABP expression occurs when the stimulation with IL-6 and PPARα-ligands takes place simultaneously. The in vivo results indicate a postprandial regulation of LFABP that correlates with the presence of IL-6. These effects may have important implications in the postprandial increase in FA uptake and intracellular trafficking in the liver. © 2013 John Wiley & Sons A/S.


PubMed | Laboratorio Of Medicina Regenerativa
Type: Journal Article | Journal: Journal of neuroscience methods | Year: 2010

The subcommissural organ (SCO) releases into the cerebrospinal fluid (CSF) large glycoproteins that polymerize forming the Reissners fibre (RF), which is involved in CSF circulation and homeostasis. We obtained high purity primary cultures of bovine secretory SCO cells and measured glycoprotein release by a reliable and sensitive ELISA method. We also analysed the effect of regulatory ligands known to control the secretory activity of the SCO. Cells cultured for short time (4h) released a high amount of glycoproteins that decreased with time. In young cultures, ATP increased and serotonin inhibited secretion rate. By contrast the acetylcholine agonist carbachol and high potassium did not evoke any detectable change in SCO glycoprotein release. These results support not only the suitability of the methodological approach but an important role of both ATP and serotonin in regulating SCO secretory activity as well.


PubMed | Laboratorio Of Medicina Regenerativa
Type: Journal Article | Journal: The Journal of comparative neurology | Year: 2010

Endocannabinoids (ECs) are important neuromodulators involved in a plethora of physiological processes such as modulation of synaptic transmission, neuroprotection, immune function, and neurodevelopment, among others. However, still lacking is a detailed study on the presence of this system in the circumventricular areas, brain structures controlling the interaction between cerebrospinal fluid and brain parenchyma. The aim of this work was to provide the anatomical basis supporting a functional role of ECs in the activity of circumventricular areas. To this end, an immunohistochemical study of the EC system in rat brain was performed. Receptors and synthesizing and degrading enzymes for ECs were widely distributed in rat ependyma and subependyma, marginal glia, and circumventricular organs (CVOs) such as the choroid plexus, subfornical organ, subcommissural organ, median eminence, and area postrema. These zones constitute barrier systems between the brain parenchyma and the ventricular or subarachnoid cerebrospinal fluid (CSF) and between the extracellular hemal milieu of CVOs and the brain parenchyma or the CSF. By immunohistochemistry and real-time polymerase chain reaction we found DAGLalpha, DAGLbeta, NAPE-PLD, MAGL, and FAAH in the ependyma. These finding suggest that the ependyma can release and clear ECs from the ventricular CSF. Subependymal astrocytes and tanycytes displayed DAGLalpha immunoreactivity but parenchymal astrocytes did not express EC-synthesizing enzymes, thus establishing a sharp distinction between these two astrocyte populations. CB1 was located in fibers innervating discrete subventricular zones such as the neurogenic striatal subventricular zone and the fourth ventricle. CB1 fibers also innervated some CVOs.

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