Оценивание равновесного реального обменного курса российского рубля

Following methodological approach proposed by Edwards, the paper estimates empirically Russia's equilibrium real exchange rate (ERER) for the period 1995–2003. ERER is defined as the relative price of non-tradables to tradables consistent with the simultaneous achievement of internal and external balances of the economy. Reduced form solution of simultaneous equations system relates ERER to a set of variables called fundamentals. These variables are identified as terms of trade, production of non-tradables, and capital flows; and the reduced form equation is estimated using Johansen cointegration technique. Effects of monetary and fiscal policies’ variables on the short-run dynamics of the real exchange rate and the speed of its adjustment towards the equilibrium are also investigated within a framework of error-correction model

Long-time effects of an experimental therapy with mesenchymal stem cells in congenital hydrocephalus

Introduction: Bone marrow-derived mesenchymal stem cells (BM-MSC) are a potential therapeutic tool due to their ability for migrating and producing neuroprotector factors when they are transplanted in other neurodegenerative diseases. Moreover, some investigations have shown that BM-MSC are able to modulate astrocyte activation and neuroprotector factor production. The aim of this study was to evaluate the long-time effects of a BM-MSC experimental therapy in the hyh mouse model of congenital hydrocephalus. Methods: BM-MSC were characterized in vitro and then transplanted into the ventricles of young hydrocephalic hyh mice, before they develop the severe hydrocephalus. Non-hydrocephalic normal mice (wt) and hydrocephalic hyh mice sham-injected (sterile saline serum) were used as controls. Samples were studied by analyzing and comparing mRNA, protein level expressions and immunoreaction related with the progression and severity of hydrocephalus. Results: Fourteen days after transplantation, hydrocephalic hyh mice with BM-MSC showed lower ventriculomegaly. In these animals, BM-MSC were found undifferentiated and spread into the periventricular astrocyte reaction. There, BM-MSC were detected producing several neuroprotector factors (BDNF, GDNF, NGF, VEGF), in the same way as reactive astrocytes. Total neocortical levels of NGF, TGF-β and VEGF were found increased in hydrocephalic hyh mice transplanted with BM-MSC. Furthermore, astrocytes showed increased expressions of aquaporin-4 (water channel protein) and Slit-2 (neuroprotective and anti-inflammatory molecule). Conclusions: BM-MSC seem to lead to recovery of the severe neurodegenerative conditions associated to congenital hydrocephalus mediated by reactive astrocytes.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. PI15/0619 (ISCIII/FEDER

Characterization and administration of bone marrow-derived mesenchymal stem cells in an animal model of congenital hydrocephalus

Bone marrow-derived mesenchymal stem cells (BM-MSC) are considered as a potential therapeutic tool in neurodegenerative diseases, due to their ability to migrate to degenerated tissues and the production of growth factors. Congenital hydrocephalus is a disorder characterized by a degeneration of the periventricular cerebral parenchyma and the white matter. In the present study, using an animal model of congenital hydrocephalus, the hyh mouse, it has been studied the capacity of the BM-MSC to reach the degenerated regions exhibiting glial reactions and their probable neuroprotector effects. The BM-MSC were isolated from two sources: a) transgenic mice expressing the monomeric red fluorescent protein (mRFP1); b) wild type mice. In the second case, the BM-MSC were labelled in vitro using bromodeoxyuridine, a fluorescent cell tracker and the lipophilic DiR. Before application, the cells were analysed using flow cytometry and immunofluorescence. The BM-MSC were injected into the retro-orbital sinus or into the lateral ventricle of hyh mice. After 24/96 hours of administration, they were detected under light, confocal and electron microscopes. The injected BM-MSC reached the degenerated periventricular regions and the disrupted neurogenic niches. They were detected in the periventricular parenchyma, around periventricular blood vessels and in the ventral meninges. Most of the applied BM-MSC expressed the glial cell-derived neurotrophic factor (GDNF), in the same way as the periventricular reactive astrocytes, suggesting a possible neuroprotector effect.Universidad de Málaga, Campus de Excelencia Internacional Andalucía Tech. Instituto de Salud Carlos III, PI12/0631 con cofinanciación FEDER

Bone marrow-derived mesenchymal stem cells characterization and transplantation in an animal model of congenital hydrocephalus

Congenital hydrocephalus is a disorder presenting a degeneration of the periventricular cerebral parenchyma and the white matter, which causes significant mortality and life-long neurological complications. There are currently no effective therapies for congenital hydrocephalus. Bone marrow-derived mesenchymal stem cells (BM-MSC) are considered as a potential therapeutic tool in neurodegenerative diseases, due to their ability to migrate to degenerated tissues and the production of growth factors. In the present study, using an animal model of congenital hydrocephalus, the hyh mouse, it has been studied the capacity of the BM-MSC to reach the degenerated regions exhibiting glial reactions and their probable neuroprotector effects. The BM-MSC were isolated from two different sources: a) transgenic mice expressing the monomeric red fluorescent protein (mRFP1); b) wild type mice. In the second case, the BM-MSC were labelled in vitro using bromodeoxyuridine, a fluorescent cell tracker and the lipophilic DiR. Before application, the cells were analysed using flow cytometry and immunofluorescence. The BM-MSC were injected into the retro-orbital sinus or into the lateral ventricle of hyh mice. After 24/96 hours of administration, the BM-MSC were detected under light, confocal and electron microscopes. The injected BM-MSC reached the degenerated periventricular regions and the disrupted neurogenic niches. They were detected in the periventricular parenchyma, around periventricular blood vessels and in the ventral meninges. Most of the applied BM-MSC expressed the glial cell-derived neurotrophic factor (GDNF), in the same way as the periventricular reactive astrocytes, suggesting a possible neuroprotector effect.FIS (Instituto de Salud Carlos III)-FEDER a AJJ. Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Bone marrow-derived mesenchymal stem cells transplantation produces a tissue recovery in hydrocephalic mice

In congenital hydrocephalus, cerebrospinal fluid accumulation is associated to ischemia/hypoxia, metabolic impairment, neuronal damage and astrocytic reaction, which cause significant mortality and life-long neurological complications. Currently, there are no effective therapies for congenital hydrocephalus. Bone marrow-derived mesenchymal stem cells (BM-MSC) are considered as a potential therapeutic tool for neurodegenerative diseases due to their ability for migrating and producing neuroprotector factors when they are transplanted. The aim of this research was to study the ability of BM-MSC to reach the degenerated regions and to detect their neuroprotector effects, using an animal model of congenital hydrocephalus, the hyh mouse. Fluorescent BM-MSC were analyzed by flow-cytometry and multilineage cell differentiation. BM-MSC were brain-ventricle injected into hyh mice. Wild-type and saline-injected hyh mice were used as controls. Inmunohistochemical, RT-PCR and High Resolution Magic Angle Spinning spectroscopy (HRMAS) analyses were carried out. After administration, integrated BM-MSC were identified inside the periventricular astrocyte reaction. They were detected producing glial-derived neuroprotector factor (GDNF), neural growth factor (NGF), and brain-derived neuroprotector factor (BDNF). Tissue recovery was detected with a reduction of apoptotic cells in the periventricular walls and of the levels of glutamate, glutamine, taurine, and creatine, all of them markers of tissue damage in hydrocephalus.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. ISCIII PI15/00619 y FEDE

Dopamine D4 receptor counteracts morphine-induced changes in M opioid receptor signaling in the striosomes of the rat caudate putamen.

Morphine is one of the most potent analgesic drugs used to relieve moderate to severe pain. After long-term use of morphine, neuroadaptive changes in the brain promotes tolerance, which result in a reduced sensitivity to most of its effects with attenuation of analgesic efficacy, and dependence, revealed by drug craving and physical or psychological manifestations of drug withdrawal. The mu opioid receptor (MOR) is critical, not only in mediating morphine analgesia, but also in addictive behaviors by the induction of a strong rewarding effect. We have previously shown that dopamine D4 receptor (D4R) stimulation counteracts morphine-induced activation of dopaminergic nigrostriatal pathway and accumulation of Fos family transcription factors in the caudate putamen (CPu). In the present work, we have studied the effect of D4R activation on MOR changes induced by morphine in the rat CPu on a continuous drug treatment paradigm, by analyzing MOR protein level, pharmacological profile, and functional coupling to G proteins. Furthermore, using conditioned place preference and withdrawal syndrome test, we have investigated the role of D4R activation on morphine-related behavioural effects. MOR immunoreactivity, agonist binding density and its coupling to G proteins are up-regulated in the striosomes by continuous morphine treatment. Interestingly, co-treatment of morphine with the dopamine D4 receptor (D4R) agonist PD168,077 fully counteracts these adaptive changes in MOR, in spite of the fact that continuous PD168,077 treatment increases the [3H]DAMGO Bmax values to the same degree as seen after continuous morphine treatment. In addition, the administration of the D4R agonist counteracts the rewarding effects of morphine, as well as the development of physical dependence. The present results give support for the existence of antagonistic functional D4R-MOR receptor-receptor interactions in the adaptive changes occurring in MOR of striosomes on continuous administration of morphine and preventing morphine-related behaviour.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

A metabolite profile reveals the presence of neurodegenerative conditions according to severity of hydrocephalus

Introduction: In obstructive congenital hydrocephalus, cerebrospinal fluid accumulation is associated with high intracranial pressure (ICP), ischemia/hypoxia, metabolic impairment, neuronal damage and astrocytic reaction. The hyh mutant mice exhibit two different forms of hydrocephalus evolution: severe and moderate. A study was carried out in hyh mice to detect a metabolite profile that define the tissue response in each hydrocephalus form. Methods: Metabolites levels in brain cortex were analyzed with 1H High Resolution Magic Angle Spinning Nuclear Magnetic Resonance (1H HR-MAS) spectroscopy. The study was complemented with ICP recording and histopathological analysis. Results: Mice with severe hydrocephalus were found to have higher ICP and stronger astrocytic reaction. Several metabolites including glutamate and glutamine were found to correlate with the severity of hydrocephalus. The whole metabolite profile may be explained based in differential astrocyte reactions, neurodegenerative and ischemic conditions. The glutamate transporter EAAT2 and the metabolite taurine were found as key histopathological markers for the damaged parenchyma. Conclusions: Spectroscopy allowed the detection of a metabolite profile related to intracranial pressure and hydrocephalus severity, and therefore can be useful to monitor the efficacy of experimental therapies. Supported by Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech, and PI15/0619 (ISCIII/FEDER).Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Supported by Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech, and PI15/0619 (ISCIII/FEDER)

Generation of periventricular reactive astrocytes overexpressing aquaporin 4 is stimulated by mesenchymal stem cell therapy

Aquaporin-4 (AQP4) plays a crucial role in brain water circulation and is considered a therapeutic target in hydrocephalus. Congenital hydrocephalus is associated with a reaction of astrocytes in the periventricular white matter both in experimental models and human cases. A previous report showed that bone marrow-derived mesenchymal stem cells (BM-MSCs) transplanted into the lateral ventricles of hyh mice exhibiting severe congenital hydrocephalus are attracted by the periventricular astrocyte reaction, and the cerebral tissue displays recovery. The present investigation aimed to test the effect of BM-MSC treatment on astrocyte reaction formation. BM-MSCs were injected into the lateral ventricles of four-day-old hyh mice, and the periventricular reaction was detected two weeks later. A protein expression analysis of the cerebral tissue differentiated the BM-MSC-treated mice from the controls and revealed effects on neural development. In in vivo and in vitro experiments, BM-MSCs stimulated the generation of periventricular reactive astrocytes overexpressing AQP4 and its regulatory protein kinase D-interacting substrate of 220 kDa (Kidins220). In the cerebral tissue, mRNA overexpression of nerve growth factor (NGF), vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1 (HIF1α), and transforming growth factor beta 1 (TGFβ1) could be related to the regulation of the astrocyte reaction and AQP4 expression. In conclusion, BM-MSC treatment in hydrocephalus can stimulate a key developmental process such as the periventricular astrocyte reaction, where AQP4 overexpression could be implicated in tissue recovery

Potential protective role of reactive astrocytes in the periventricular parenchyma in congenital hydrocephalus

Background Cerebrospinal fluid accumulation in hydrocephalus produces an elevation of intraventricular pressure with pathological consequences on the periventricular brain parenchyma including ischemia, oedema, oxidative stress, and accumulation of metabolic waste products. Here we studied in the hyh mouse, an animal model of congenital hydrocephalus, the role of reactive astrocytes in this clinical degenerative condition. Materials and Methods Wild type and hydrocephalic hyh mice at 30 days of postnatal age were used. Three metabolites related to the oxidative and neurotoxic conditions were analysed in ex vivo samples (glutathione, glutamine and taurine) using High Resolution Magic Angle Spinning (HR-MAS). Glutathione synthetase and peroxidase, glutamine synthetase, kidney-type glutaminase (KGA), and taurine/taurine transporter were immunolocated in brain sections. Results Levels of the metabolites were remarkably higher in hydrocephalic conditions. Glutathione peroxidase and synthetase were both detected in the periventricular reactive astrocytes and neurons. Taurine was mostly found free in the periventricular parenchyma and in the reactive astrocytes, and the taurine transporter was mainly present in the neurons located in such regions. Glutamine synthetase was found in reactive astrocytes. Glutaminase was also detected in the reactive astrocytes and in periventricular neurons. These results suggest a possible protective response of reactive astrocytes against oxidative stress and neurotoxic conditions. Conclusions Astrocyte reaction seems to trigger an anti-oxidative and anti-neurotoxic response in order to ameliorate pathological damage in periventricular areas of the hydrocephalic mice.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. PI15-00619 to AJJ

Dopamine D4 receptor is a regulator of morphine-induced plasticity in the rat dorsal striatum

Long-term exposition to morphine elicits structural and synaptic plasticity in reward-related regions of the brain, playing a critical role in addiction. However, morphine-induced neuroadaptations in the dorsal striatum have been poorly studied despite its key function in drug-related habit learning. Here, we show that prolonged treatment with morphine triggered the retraction of the dendritic arbor and the loss of dendritic spines in the dorsal striatal projection neurons (MSNs). In an attempt to extend previous findings, we also explored whether the dopamine D4 receptor (D4R) could modulate striatal morphine-induced plasticity. The combined treatment of morphine with the D4R agonist PD168,077 produced an expansion of the MSNs dendritic arbors and restored dendritic spine density. At the electrophysiological level, PD168,077 in combination with morphine altered the electrical properties of the MSNs and decreased their excitability. Finally, results from the sustantia nigra showed that PD168,077 counteracted morphine-induced upregulation of μ opioid receptors (MOR) in striatonigral projections and downregulation of G protein-gated inward rectifier K+ channels (GIRK1 and GIRK2) in dopaminergic cells. The present results highlight the key function of D4R modulating morphine-induced plasticity in the dorsal striatum. Thus, D4R could represent a valuable pharmacological target for the safety use of morphine in pain management.This research was funded by: Junta de Andalucía (Spain) (P09-CVI-4702 and CTS-0161 to A.R); French National Research Agency (ANR-15-CE37-0006 to J.B. and A.T.); LABEX BRAIN (ANR-10-LABX-43 to J.B. and A.T.); Basque Government (Spain) (PUE21-03 to C.M); UPV/EHU (Spain) (COLAB20/07 to C.M). The University of Málaga, University of Bordeaux and CNRS provided infrastructural support