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Larrosa-Campo D.,Hospital Universitario Central Of Asturias | Larrosa-Campo D.,Institute Neurociencias Del Principado Of Asturias | Ramon-Carbajo C.,Hospital Universitario Central Of Asturias | Ramon-Carbajo C.,Institute Neurociencias Del Principado Of Asturias | And 8 more authors.
Revista de Neurologia | Year: 2015

Introduction. The pathophysiology underlying the association between migraine and other non-atherosclerotic vascular diseases is largely unknown. Endothelial dysfunction has been proposed as a common link. Besides, endothelial dysfunction is considered as a predictor of structural changes in the arterial walls. Aim. To review the current knowledge about the functional (endothelial dysfunction) and structural (arterial stiffness and atherosclerotic diseases) arterial properties associated with migraine. Development. Studies of biological markers of endothelial dysfunction in peripheral blood, systemic and cerebral vasoreactivity, arterial stiffness indexes and direct visualization of macroscopic changes in the arterial wall have shown differences between patients with and without migraine, as well as between the different migraine subtypes. Conclusions. Endothelial dysfunction, as a predictor of structural changes in arteries, has been proposed as an early marker for vascular pathology associated with migraine. In migraine patients there is an increase of biomarkers of endothelial dysfunction, but the correlation with vasoreactivity studies does not allow definite conclusions. Available data do not allow to conclude that migraine is associated with macroscopic alterations outside the cerebral arterial bed. © 2015 Revista de Neurología.


Arias N.,University of Cambridge | Arias N.,Institute Neurociencias Del Principado Of Asturias | Fidalgo C.,University of Cagliari | Fidalgo C.,Institute Neurociencias Del Principado Of Asturias | And 4 more authors.
Neuroscience Letters | Year: 2015

Reversal learning has been studied as the process of learning to inhibit previously rewarded actions. These behavioral studies are usually performed during the day, when animals are in their daily period rest. However, how day or night affects spatial reversal learning and the brain regions involved in the learning process are still unknown. We conducted two experiments using the Morris Water Maze under different light-conditions: naïve group (CN, n= 8), day group (DY, n= 8), control DY group (CDY, n= 8) night group (NG, n= 8), and control NG group (CNG, n= 7). Distance covered, velocity and latencies to reach the platform were examined. After completing these tasks, cytochrome c-oxidase activity (CO) in several brain limbic system structures was compared between groups. There were no behavioral differences in the time of day when the animals were trained. However, the metabolic brain consumption was higher in rats trained in the day condition. This CO increase was supported by the prefrontal cortex, thalamus, dorsal and ventral striatum, hippocampus and entorhinal cortex, revealing their role in the performance of the spatial reversal learning task. Finally, the orbitofrontal cortex has been revealed as a key structure in reversal learning execution. © 2015 Elsevier Ireland Ltd.


Arias N.,University of Oviedo | Arias N.,Institute Neurociencias Del Principado Of Asturias | Mendez M.,University of Oviedo | Mendez M.,Institute Neurociencias Del Principado Of Asturias | And 2 more authors.
Neuroscience Letters | Year: 2014

The present study investigated the behavioural performance and the contributions of different brain regions on a spatial task performed by Wistar rats in the Cincinnati water maze (CWM) in two conditions: one where both distal and proximal visual cues were available (CWM-light group, n= 7) and another where visual cues were eliminated by testing in complete darkness (CWM-dark group, n= 7). There were differences in the behavioural performance. Energetic brain metabolism revealed significant differences in the infralimbic, orbitofrontal cortex and anterodorsal striatum. At the same time different brain networks were found. The CWM-light group showed a relationship between the orbitofrontal cortex and medial septum, whereas the CWM-dark group revealed three different networks involving the prefrontal cortex, ventral striatum, hippocampus and amygdala nuclei. The study shows that brain activation differs in these two conditions. © 2014 Elsevier Ireland Ltd.


Arias N.,University of Cambridge | Arias N.,Institute Neurociencias Del Principado Of Asturias | Mendez M.,University of Oviedo | Mendez M.,Institute Neurociencias Del Principado Of Asturias | And 2 more authors.
Lasers in Medical Science | Year: 2016

Minimal hepatic encephalopathy (MHE) has been shown to affect daily functioning, quality of life, driving and overall mortality. However, little is known about treating or diagnosing early impairments involved in MHE. We studied one of its precipitating factors, portal hypertension. The purpose was to evaluate an enhancement in neuronal metabolism through low-light-level therapy (LLLT) and whether this therapy has effects on behavioural task acquisition. Rats were trained to perform a stimulus-response task using the Morris water maze. Three groups of animals were used: a SHAM (sham-operated) group (n = 7), a portal hypertension (PH) group (n = 7) and a PH + LLLT group (n = 7). The triple portal vein ligation method was used to create an animal model of the early developmental phase of HE, and then the animals were exposed to 670 + 10 nm LED light at a dose of 9 J/cm2 once a day for 7 days. The metabolic activity of the brains was studied with cytochrome c oxidase histochemistry. There were differences in behavioural performance, with an improvement in the PH + LLLT group. Energetic brain metabolism revealed significant differences between the groups in all the brain structures analysed, except the anterodorsal thalamus. At the same time, in different brain networks, the PH group showed a more complicated relationship among the structures, while the SHAM and PH + LLLT groups had similar patterns. In this study, we provide the first preliminary insights into the validity of LLLT as a possible intervention to improve memory under minimal hepatic encephalopathy conditions. © 2016 Springer-Verlag London


Arias N.,University of Cambridge | Arias N.,Institute Neurociencias Del Principado Of Asturias | Mendez M.,University of Oviedo | Mendez M.,Institute Neurociencias Del Principado Of Asturias | And 3 more authors.
Brain Research | Year: 2015

Mastering the Morris water maze (MWM) requires the animal to consolidate, retain and retrieve spatial localizations of relevant visual cues. However, it is necessary to investigate whether a reorganization of the neural networks takes place when part of the spatial information is removed. We conducted four experiments using the MWM. A classical reference memory procedure was performed over five training days, RM5 (n=7), and eight days, RM8 (n=7), with the whole room and all the spatial cues presented. Another group of animals were trained in the same protocol, but they received an additional day of training with only partial cues, PC (n=8). Finally, a third group of animals performed the classical task, followed by an overtraining with partial cues for four more days, OPC (n=8). After completing these tasks, cytochrome c-oxidase activity (CO) in several brain limbic system structures was compared between groups. In addition, c-Fos positive cells were measured in the RM5, RM8, PC and OPC groups. No significant differences were found among the four groups in escape latencies or time spent in the target quadrant. CO revealed involvement of the prefrontal and parietal cortices, dorsal and ventral striatum, CA1 and CA3 subfields of the dorsal hippocampus, basolateral and lateral amygdala, and mammillary nuclei in the PC group, compared to the RM group. In the OPC group, involvement of the ventral striatum and anteroventral thalamus and the absence of amygdala involvement were revealed, compared to the PC group. C-Fos results highlighted the role of the prefrontal cortex, dorsal striatum, anterodorsal thalamus and CA3 in the PC group, compared to the OPC, RM5 and RM8 groups. The animals were able to find the escape platform even when only a portion of the space where the cues were placed was available. Although the groups did not differ behaviorally, energetic brain metabolism and immediate early gene expression revealed the engagement of different neural structures in the groups that received more training without the entire surrounding space. © 2015 Elsevier B.V.


Arias N.,University of Oviedo | Arias N.,Institute Neurociencias Del Principado Of Asturias | Fidalgo C.,University of Oviedo | Felipo V.,Centro Investigacion Principe Felipe | And 2 more authors.
Metabolic Brain Disease | Year: 2014

Ammonia is thought to be central in the development of hepatic encephalopathy. However, the specific relation of ammonia with brain energy depletions and learning has not been studied. Our work attempts to reproduce an increase in rat cerebral ammonia level, study the hyperamonemic animals' performance of two learning tasks, an allocentric (ALLO) and a cue guided (CG) task, and elucidate the contribution of hyperammonemia to the differential energy requirements of the brain limbic system regions involved in these tasks. To assess these goals, four groups of animals were used: a control (CHA) CG group (n = 10), a CHA ALLO group (n = 9), a hyperammonemia (HA) CG group (n = 7), and HA ALLO group (n = 8). Oxidative metabolism of the target brain regions were assessed by histochemical labelling of cytochrome oxidase (C.O.). The behavioural results revealed that the hyperammonemic rats were not able to reach the behavioural criterion in either of the two tasks, in contrast to the CHA groups. The metabolic brain consumption revealed increased C.O. activity in the anterodorsal thalamus when comparing the HA ALLO group with the CHA ALLO group. Significant differences between animals trained in the CG task were observed in the prelimbic, infralimbic, parietal, entorhinal and perirhinal cortices, the anterolateral and anteromedial striatum, and the basolateral and central amygdala. Our findings may provide fresh insights to reveal how the differential damage to the brain limbic structures involved in these tasks differs according to the degree of task difficulty. © 2014 Springer Science+Business Media.


Sampedro-Piquero P.,University of Oviedo | Sampedro-Piquero P.,Institute Neurociencias Del Principado Of Asturias | Arias J.L.,University of Oviedo | Arias J.L.,Institute Neurociencias Del Principado Of Asturias | And 2 more authors.
Experimental Gerontology | Year: 2014

Our aim was to assess the changes in the Synapsin I and glucocorticoid receptor (GR) expression induced by behavioral testing in the dorsal and ventral hippocampi of standard and enriched aged Wistar rats. The environmental enrichment (EE) was carried out 3. h/day over a period of two months and then, the rats were tested in the elevated zero-maze (EZM) and radial-arm water maze (RAWM). Behavioral results showed that, even at an advanced age, EE was able to reduce anxiety-related behaviors and improve the performance in the RAWM. Regarding the neurobiological data, Synapsin I expression in the dorsal CA3, but not in the ventral, was enhanced both in enriched and standard rats when they performed the behavioral testing. Interestingly, the EE exposure was enough to increase Synapsin I in the ventral CA3. The analysis of GR in the dorsal hippocampus showed an increase of this receptor in the dDG both in enriched and standard rats when they performed the behavioral testing, whereas in the dCA1 and dCA3, the effect of the testing depended on the previous housing condition. In the ventral region, we found that the effects of EE were higher because on the one hand, the GR expression induced by the behavioral testing was enhanced in the dSUB, vCA1 and vCA3 when the rats were previously enriched and on the other hand, EE, regardless of the behavioral testing, increased the GR expression in the vDG and vSUB. Therefore, our results suggest that the effect of the behavioral testing on the neurobiological mechanisms studied is different depending on the previous housing condition of aged rats. © 2014 Elsevier Inc.


Arias N.,University of Oviedo | Arias N.,Institute Neurociencias Del Principado Of Asturias | Mendez M.,University of Oviedo | Mendez M.,Institute Neurociencias Del Principado Of Asturias | And 2 more authors.
Neuroscience | Year: 2015

The hippocampus has been established as a site of plasticity during the acquisition of spatial memory. The memory for spatial locations is impaired in patients who develop hepatic encephalopathy (HE). We wondered how the hippocampus can manage different hippocampal-dependent tasks in a type B model of the early evolutive phases of HE induced by triple portal vein ligation. We used a one-trial object-place recognition task that involves making judgements about whether a stimulus was encountered before in that location and a reversal learning task performed in the Morris water maze that involves reward-guided behavior and decision making. Our behavioral results showed impairments in the acquisition of both tasks by the portal hypertension group compared with the sham-operated group. To label brain areas related to these tasks, we marked the expression of the c-Fos protein and revealed high c-Fos immunoreactivity in cornu ammonis 1 (CA1), cornu ammonis 3 (CA3) and entorhinal (Ent) cortex of the PH group compared with the SHAM group in the object-place recognition task and a decrease in c-Fos-positive cells in the reversal task in the CA1, CA3, dentate gyrus (DG), cingulate (CG), prelimbic (PL), and infralimbic (IL) cortices in the PH group compared with the SHAM group. In conclusion, the study corroborated the pivotal role of the hippocampus in spatial memory deficits found in the early stages of type B HE and noted its differential contribution in each of the tasks. © 2014 IBRO.


Arias N.,University of Cambridge | Arias N.,Institute Neurociencias Del Principado Of Asturias | Mendez M.,University of Oviedo | Mendez M.,Institute Neurociencias Del Principado Of Asturias | And 2 more authors.
Behavioural Brain Research | Year: 2015

Contextual memory implies recognition based on the association between past and present events experienced. It is important for daily functioning and dysfunctional in many neuropsychological disturbances. The network related to this memory is still open for debate, even though it has been associated with medial temporal lobe regions, including the perirhinal, entorhinal and temporal association cortices, as well as the hippocampus and prefrontal cortex. Our work tries to elucidate whether a change in the context, such as differences in the amount of stimuli presented on the walls and floor of an open field during object exploration, affects the recognition of an object that has been experienced before, and whether this context manipulation could be linked to changes in c-Fos expression. For this purpose, we used a one-trial novel-object recognition task. The animals were divided into two different experimental conditions; in the OR-NORMAL group, the sample and probe test were performed in the same context. However, in the OR-CONTEXT group, the probe test was performed in a different context. Our results showed that the OR-NORMAL group presented a greater exploration of objects than the OR-CONTEXT group. However, both groups presented significant exploration of the novel object. To label the brain regions involved in novel-object recognition under these conditions, we marked the expression of c-Fos protein. Results suggest that a neural circuit that includes the hippocampus, entorhinal and temporal association cortices is involved in the recognition of the novel-object in a novel context. © 2015 Elsevier B.V..

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