Artículos (Fisiología)
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Artículo A Cholinergic Synaptically Triggered Event Participates in the Generation of Persistent Activity Necessary for Eye Fixation(Society for Neuroscience, 2004) Navarro López, Juan de Dios; Alvarado, Juan Carlos; Márquez Ruiz, Javier; Escudero González, Miguel; Delgado García, José María; Yajeya, Javier; Universidad de Sevilla. Departamento de Fisiología; European Union (UE); Ministerio de Educación y Cultura (MEC). EspañaAn exciting topic regarding integrative properties of the nervous system is how transient motor commands or brief sensory stimuli are able to evoke persistent neuronal changes, mainly as a sustained, tonic action potential firing. A persisting firing seems to be necessary for postural maintenance after a previous movement. We have studied in vitro and in vivo the generation of the persistent neuronal activity responsible for eye fixation after spontaneous eye movements. Rat sagittal brainstem slices were used for the intracellular recording of prepositus hypoglossi (PH) neurons and their synaptic activation from nearby paramedian pontine reticular formation (PPRF) neurons. Single electrical pulses applied to the PPRF showed a monosynaptic glutamatergic projection on PH neurons, acting on AMPA-kainate receptors. Train stimulation of the PPRF area evoked a sustained depolarization of PH neurons exceeding (by hundreds of milliseconds) stimulus duration. Both duration and amplitude of this sustained depolarization were linearly related to train frequency. The train-evoked sustained depolarization was the result of interaction between glutamatergic excitatory burst neurons and cholinergic mesopontine reticular fibers projecting onto PH neurons, because it was prevented by slice superfusion with cholinergic antagonists and mimicked by cholinergic agonists. As expected, microinjections of cholinergic antagonists in the PH nucleus of alert behaving cats evoked a gaze-holding deficit consisting of a re-centering drift of the eye after each saccade. These findings suggest that a slow, cholinergic, synaptically triggered event participates in the generation of persistent activity characteristic of PH neurons carrying eye position signals.Artículo A chronically implantable device for the controlled delivery of substances, and stimulation and recording of activity in severed nerves(Elsevier, 2008-01-30) Davis López de Carrizosa, María América; Tena, Juan J.; Benítez Temiño, Beatriz; Morado Díaz, Camilo José; Pastor Loro, Ángel Manuel; Rodríguez de la Cruz, Rosa María; Universidad de Sevilla. Departamento de Fisiología; Ministerio de Educación y Ciencia (MEC). España; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Junta de AndalucíaWe describe the use of an implantable device for peripheral nerves that allows chronic simultaneous delivery of small volumes of solution, recording of both field and multiunit potentials, and electrical stimulation. This custom-made multifunctional device was attached to the cut end of the abducens (VIth) nerve for stimulation, recording and injection purposes. Our device consists of a polyethylene chamber with two electrodes that can be used for stimulation and recording and two Teflon tubes that serve as inlet and outlet for administering chemicals to the nerve fitted inside. Since the device is implanted in a retro-orbital position, we herein will refer to it as an intraorbitary device (IOD). The applicability of the IOD is demonstrated with an electrophysiological and anatomical account of the properties of the abducens nerve. Furthermore, it is shown that certain neuronal discharge properties can be inferred from the nerve recordings. The IOD can also be efficiently used for the delivery of small volume of pharmacological substances or conventional retrograde markers.Artículo “A Concurso un congreso”. Innovación docente en la asignatura “Fisiología de la digestión”(Universidad de Granada, 2014) Ojeda Murillo, María Luisa; Nogales Bueno, Fátima; Carreras Sánchez, Olimpia; Universidad de Sevilla. Departamento de FisiologíaArtículo A metagenome-wide association study of HIV disease progression in HIV controllers(Elsevier, 2023) Real, Luis Miguel; Sáez, María E.; Corma Gómez, Anaïs; González Pérez, Antonio; Thorball, Christian; Ruiz Laza, Rocío; Jiménez León, María Reyes; González-Serna Martín, Manuel Alejandro; Bachiller, Sara; Ruiz Mateos, Ezequiel; Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Universidad de Sevilla. Departamento de Fisiología; Junta de Andalucía; European Union (UE); European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Instituto de Salud Carlos III; Agencia Estatal de Investigación. EspañaSome HIV controllers experience immunologic progression with CD4+ T cell decline. We aimed to identify genetic factors associated with CD4+ T cell lost in HIV controllers. A total of 561 HIV controllers were included, 442 and 119 from the International HIV controllers Study Cohort and the Swiss HIV Cohort Study, respectively. No SNP or gene was associated with the long-term non-progressor HIV spontaneous control phenotype in the individual GWAS or in the meta-analysis. However, SNPs previously associated with natural HIV control linked to HLA-B (rs2395029 [p = 0.005; OR = 1.70], rs59440261 [p = 0.003; OR = 1.78]), MICA (rs112243036 [p = 0.011; OR = 1.45]), and PSORS1C1 loci (rs3815087 [p = 0.017; OR = 1.39]) showed nominal association with this phenotype. Genetic factors associated with the long-term HIV controllers without risk of immunologic progression are those previously related to the overall HIV controller phenotype.Artículo A novel PKC activating molecule promotes neuroblast differentiation and delivery of newborn neurons in brain injuries(Springer Nature, 2020) Domínguez García, Samuel; Geribaldi Doldán, Noelia; Gómez Oliva, Ricardo; Ruiz, Felix A.; Carrascal Moreno, María Livia; Bolívar, Jorge; Verástegui, Cristina; García Alloza, Mónica; Macías Sánchez, Antonio J.; Hernández Galán, Rosario; Nuñez Abades, Pedro Antonio; Universidad de Sevilla. Departamento de Fisiología; Ministerio de Ciencia, Innovación y Universidades (MICINN). EspañaNeural stem cells are activated within neurogenic niches in response to brain injuries. This results in the production of neuroblasts, which unsuccessfully attempt to migrate toward the damaged tissue. Injuries constitute a gliogenic/non-neurogenic niche generated by the presence of anti-neurogenic signals, which impair neuronal differentiation and migration. Kinases of the protein kinase C (PKC) family mediate the release of growth factors that participate in different steps of the neurogenic process, particularly, novel PKC isozymes facilitate the release of the neurogenic growth factor neuregulin. We have demonstrated herein that a plant derived diterpene, (EOF2; CAS number 2230806-06-9), with the capacity to activate PKC facilitates the release of neuregulin 1, and promotes neuroblasts differentiation and survival in cultures of subventricular zone (SVZ) isolated cells in a novel PKC dependent manner. Local infusion of this compound in mechanical cortical injuries induces neuroblast enrichment within the perilesional area, and noninvasive intranasal administration of EOF2 promotes migration of neuroblasts from the SVZ towards the injury, allowing their survival and differentiation into mature neurons, being some of them cholinergic and GABAergic. Our results elucidate the mechanism of EOF2 promoting neurogenesis in injuries and highlight the role of novel PKC isozymes as targets in brain injury regeneration.Artículo A Single Intraventricular Injection of VEGF Leads to Long-Term Neurotrophic Effects in Axotomized Motoneurons(Society for Neuroscience, 2020) Martín Calvo, Paula; Rodríguez de la Cruz, Rosa María; Pastor Loro, Ángel Manuel; Universidad de Sevilla. Departamento de Fisiología; Ministerio de Economía y Competitividad (MINECO). España; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Ministerio de Ciencia, Innovación y Universidades (MICINN). EspañaVascular endothelial growth factor (VEGF) has been recently demonstrated to induce neuroprotective and synaptotrophic effects on lesioned neurons. Hitherto, the administration of VEGF in different animal models of lesion or disease has been conducted following a chronic protocol of administration. We questioned whether a single dose of VEGF, administered intraventricularly, could induce long-term neurotrophic effects on injured motoneurons. For this purpose, we performed in cats the axotomy of abducens motoneurons and the injection of VEGF into the fourth ventricle in the same surgical session and investigated the discharge characteristics of axotomized and treated motoneurons by single-unit extracellular recordings in the chronic alert preparation. We found that injured motoneurons treated with a single VEGF application discharged with normal characteristics, showing neuronal eye position (EP) and velocity sensitivities similar to control, thereby preventing the axotomy-induced alterations. These effects were present for a prolonged period of time (50 d) after VEGF administration. By confocal immunofluorescence we also showed that the synaptic stripping that ensues lesion was not present, rather motoneurons showed a normal synaptic coverage. Moreover, we demonstrated that VEGF did not lead to any angiogenic response pointing to a direct action of the factor on neurons. In summary, a single dose of VEFG administered just after motoneuron axotomy is able to prevent for a long time the axotomy-induced firing and synaptic alterations without any associated vascular sprouting. We consider that these data are of great relevance due to the potentiality of VEGF as a therapeutic agent in neuronal lesions and diseases.Artículo A Single Zinc Finger Motif in the Silencing Factor Rest Represses the Neural-Specific Type II Sodium Channel Promoter.(PNAS, 1997) Peral Rubio, María José; Tapia Ramírez, José; Eggen, Bart J. L.; Toledo Aral, Juan José; Mandel, Gail; Universidad de Sevilla. Departamento de FisiologíaThe type II voltage-dependent sodium chan- nel is present in neuronal cells, where it mediates the prop- agationofnerveimpulses.RestrictedexpressionofthetypeII sodium channel gene to neurons is due, at least in part, to binding of the repressor protein REST (also termed NRSF or XBR) to the RE1 (also called NRSE) sequence in the type II sodium channel gene. Previous studies have shown that a domain in REST containing eight GL1-Kru ̈ppel zinc finger motifs mediates DNA binding. Deletional and GAL4-fusion geneanalysesnowrevealrepressordomainsthatlieoutsideof the DNA-binding domain in both the amino and carboxyl termini of REST. Mutational analysis further identifies a single zinc finger motif in the carboxyl-terminal domain as beingessentialforrepressingtypeIIsodiumchannelreporter genes. These studies reveal two domains in REST that may mediate interactions with other proteins involved in restrict- ingexpressionofalargesetofgenestothevertebratenervous system.Artículo Acción tutorial en el EEES en la Facultad de Farmacia de la US: 4 años de experiencia de un programa de alumnos tutores(2010) Fernández Arévalo, María Mercedes; Álvarez Fuentes, Josefa; Ferrero Rodríguez, Carmen; Marín Rubio, Pedro; Mate Barrero, Alfonso; Millán Jiménez, Mónica; Morales González, Julia; Peral Rubio, María José; Pichardo Sánchez, Silvia; Gutiérrez-Praena, Daniel; Vega Pérez, José Manuel; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Universidad de Sevilla. Departamento de Ecuaciones Diferenciales y Análisis Numérico; Universidad de Sevilla. Departamento de Fisiología; Universidad de Sevilla. Departamento de Biología Vegetal y Ecología; Universidad de Sevilla. Departamento de Nutrición y Bromatología, Toxicología y Medicina Legal; Universidad de Sevilla. Departamento de Química Orgánica y FarmacéuticaLa Facultad de Farmacia de la Universidad de Sevilla (US) tiene en marcha un Programa de Alumnos Tutores desde 2006/07 con el objetivo de que alumnos de cursos superiores (AATT) tutelen a alumnos de nuevo ingreso (1x3). Pretende generar una actitud responsable en los AATT y favorecerles el desarrollo de habilidades sociales, objetivos cualitativos dentro de la educación universitaria que sirven como preparación previa a su inserción en el mundo laboral. La actividad es supervisada por Profesores Tutores (1x3) que analizan la evolución de ambos grupos de alumnos. Es una supervisión activa a través de distintas vías de acción para ayudar a la consecución de objetivos, tales como entrevistas periódicas, revisión de informes, acciones de apoyo como charlas sobre técnicas de estudio, coloquios sobre salidas laborales, exposiciones de las experiencias personales de algunos alumnos recientemente egresados, gestión estratégica de búsqueda de empleo, elaboración de portafolios,… Con respecto a la evolución del programa, el número de profesores ha crecido moderadamente llegando a una situación estable, mientras que el número de alumnos, tanto tutores como tutelados, ha crecido en un ritmo constante acorde a las restricciones indicadas. Los resultados son muy positivos, entendiéndose que el proyecto se enmarca en un contexto más cualitativo que cuantitativo y que el principal objetivo es el robustecimiento de la experiencia y asentar una dinámica de apoyo hacia los alumnos de nuevo ingreso y de planificación de tareas, tutela y responsabilidad en general de los alumnos tutores.Artículo Acute Colon Inflammation Triggers Primary Motor Cortex Glial Activation, Neuroinflammation, Neuronal Hyperexcitability, and Motor Coordination Deficits(Multidisciplinary Digital Publishing Institute (MDPI), 2022) Carrascal Moreno, María Livia; Vázquez Carretero, María Dolores; García Miranda, Pablo; Fontán Lozano, Ángela del Carmen; Calonge Castrillo, María Luisa; Ilundáin Larrañeta, María Anunciación Ana; Castro, Carmen; Núñez Abades, Pedro Antonio; Peral Rubio, María José; Universidad de Sevilla. Departamento de Fisiología; Ministerio de Ciencia e Innovación (MICIN). España; Agencia Estatal de Investigación. EspañaNeuroinflammation underlies neurodegenerative diseases. Herein, we test whether acute colon inflammation activates microglia and astrocytes, induces neuroinflammation, disturbs neuron intrinsic electrical properties in the primary motor cortex, and alters motor behaviors. We used a rat model of acute colon inflammation induced by dextran sulfate sodium. Inflammatory mediators and microglial activation were assessed in the primary motor cortex by PCR and immunofluorescence assays. Electrophysiological properties of the motor cortex neurons were determined by whole-cell patch-clamp recordings. Motor behaviors were examined using open-field and rotarod tests. We show that the primary motor cortex of rats with acute colon inflammation exhibited microglial and astrocyte activation and increased mRNA abundance of interleukin-6, tumor necrosis factor-alpha, and both inducible and neuronal nitric oxide synthases. These changes were accompanied by a reduction in resting membrane potential and rheobase and increased input resistance and action potential frequency, indicating motor neuron hyperexcitability. In addition, locomotion and motor coordination were impaired. In conclusion, acute colon inflammation induces motor cortex microglial and astrocyte activation and inflammation, which led to neurons’ hyperexcitability and reduced motor coordination performance. The described disturbances resembled some of the early features found in amyotrophic lateral sclerosis patients and animal models, suggesting that colon inflammation might be a risk factor for developing this disease.Artículo Adaptation of Electrolytes and Fluid Transport in Rat Small and Large lntestine After Distal Small Bowel Resection(Consejo Superior de Investigaciones Ciéntificas, 1988-06) Ilundáin Larrañeta, María Anunciación Ana; Vázquez Cueto, Carmen María; Molina, M.T.; Universidad de Sevilla. Departamento de FisiologíaNa+ , e¡- and water transpon werc studied in jejunum , caecum and colon after either 50 % or 80 % of small bowel resection (SBR). Four weeks after surgery, dry and wet weights, ner absorprion in vivo of sodiu m , chloride and water were detem1ined . There was a significant intestinal growth after 50 % or 80 % SBR exccpt for the colon w hich only showed increased tissue mass after 80 % SBR. Net transpon was stimulated both, pcr organ and per unir mass. In the small intestine and caecum both organ growth and chan ges in cell function appear ro be in volved in the adaptiv e response, regardless th e extcnt of the small intestine resected. In the colon, com pensatory grow th appear ro contribute to rh e adaptive response only after 80 % SBR, whilst t he transpon function of the colonocytes seems to be stimulatcd after both types of SBR .Artículo AdipoRon enhances healthspan in middle‐aged obese mice: striking alleviation of myosteatosis and muscle degenerative markers(Wiley Open Access, 2023) Selvais, Camille M.; Davis López de Carrizosa, María América; Nachit, Maxime; Versele, Romain; Dubuisson, Nicolas; Noel, Laurence; Abou-Samra, Michel; Universidad de Sevilla. Departamento de Fisiología; University College de Londres (UCL). UK; Société Francophone du Diabète (SFD). Francia; National Fund for Scientific Research (FNRS). BélgicaBackgroundObesity among older adults has increased tremendously. Obesity accelerates ageing and predisposes toage-related conditions and diseases, such as loss of endurance capacity, insulin resistance and features of the metabolicsyndrome. Namely, ectopic lipids play a key role in the development of nonalcoholic fatty liver disease (NAFLD) andmyosteatosis, two severe burdens of ageing and metabolic diseases. Adiponectin (ApN) is a hormone, mainly secretedby adipocytes, which exerts insulin-sensitizing and fat-burning properties in several tissues including the liver and themuscle. Its overexpression also increases lifespan in mice. In this study, we investigated whether an ApN receptor ag-onist, AdipoRon (AR), could slow muscle dysfunction, myosteatosis and degenerative muscle markers in middle-agedobese mice. The effects on myosteatosis were compared with those on NAFLD.MethodsThree groups of mice were studied up to 62 weeks of age: One group received normal diet (ND), another,high-fat diet (HFD); and the last, HFD combined with AR given orally for almost 1 year. An additional group of youngmice under an ND was used. Treadmill tests and micro-computed tomography (CT) were carried out in vivo. Histolog-ical, biochemical and molecular analyses were performed on tissues ex vivo. Bodipy staining was used to assessintramyocellular lipid (IMCL) and lipid droplet morphology.ResultsAR did not markedly alter diet-induced obesity. Yet, this treatment rescued exercise endurance in obese mice(up to 2.4-fold,P<0.05), an event that preceded the improvement of insulin sensitivity. Dorsal muscles and liver den-sities, measured by CT, were reduced in obese mice ( 42% and 109%, respectively,P<0.0001), suggesting fatty in-filtration. This reduction tended to be attenuated by AR. Accordingly, AR significantly mitigated steatosis and cellularballooning at liver histology, thereby decreasing the NALFD activity score ( 30%,P<0.05). AR also strikingly reversedIMCL accumulation either due to ageing in oxidativefibres (types 1/2a, soleus) or to HFD in glycolytic ones (types2x/2b, extensor digitorum longus) ( 50% to 85%,P<0.05 or less). Size of subsarcolemmal lipid droplets, knownto be associated with adverse metabolic outcomes, was reduced as well. Alleviation of myosteatosis resulted from im-proved mitochondrial function and lipid oxidation. Meanwhile, AR halved aged-related accumulation of dysfunctionalproteins identified as tubular aggregates and cylindrical spirals by electron microscopy (P<0.05).ConclusionsLong-term AdipoRon treatment promotes‘healthy ageing’in obese middle-aged mice by enhancing en-durance and protecting skeletal muscle and liver against the adverse metabolic and degenerative effects of ageingand caloric excess.Artículo Adipose Tissue Homeostasis Orchestrates the Oxidative, Energetic, Metabolic and Endocrine Disruption Induced by Binge Drinking in Adolescent Rats(Wiley-Blackwell, 2023) Romero Herrera, Inés; Nogales Bueno, Fátima; Gallego López, María del Carmen; Díaz Castro, Javier; Moreno Fernández, Jorge; Ochoa, Julio José; Carreras Sánchez, Olimpia; Ojeda Murillo, María Luisa; Universidad de Sevilla. Departamento de Fisiología; Junta de Andalucía; Universidad de SevillaBinge drinking (BD) is the most common alcohol consumption model for adolescents, and has recently been related to the generation of high oxidation and insulin resistance (IR). White adipose tissue (WAT) is a target organ for insulin action that regulates whole-body metabolism by secreting adipokines. The present study aimed to analyse the oxidative, inflammatory, energetic and endocrine profile in the WAT of BD-exposed adolescent rats, to obtain an integrative view of insulin secretion and WAT in IR progression. Two groups of male adolescent rats were used: control (n = 8) and BD (n = 8). An intermittent i.p. BD model (20% v/v) was used during 3 consecutive weeks. BD exposure led to a pancreatic oxidative imbalance, which was joint to high insulin secretion by augmenting deacetylase sirtuin-1 (SIRT-1) pancreatic expression and serum adipsin levels. However, BD rats had hyperglycaemia and high homeostasis model assessment of insulin resistance value (HOMA-IR). BD exposure in WAT increased lipid oxidation, as well as decreased insulin receptor substrate 1 (IRS-1) and AKT expression, sterol regulatory element-binding protein 1 (SREBP1), forkhead box O3A (FOXO3a) and peroxisome proliferator-activated receptor γ (PPARγ), and adipocyte size. BD also affected the expression of proteins related to energy balance, such as SIRT-1 and AMP activated protein kinase (AMPK), affecting the adipokine secretion profile (increasing resistin/adiponectin ratio). BD altered the entire serum lipid profile, increasing the concentration of free fatty acids. In conclusion, BD led to an oxidative imbalance and IR process in WAT, which modified the energy balance in this tissue, decreasing the WAT lipogenic/lipolytic ratio, affecting adipokine secretion and the systemic lipid profile, and contributing to the progression of IR. Therefore, WAT is key in the generation of metabolic and endocrine disruption after BD exposure during adolescence in rats. (Figure presented.). Key points: Adolescent rat binge drinking (BD) exposure leads to hepatic and systemic oxidative stress (OS) via reactive oxygen species generation, causing hepatic insulin resistance (IR) and altered energy metabolism. In the present study, BD exposure in adolescent rats induces OS in the pancreas, with increased insulin secretion despite hyperglycaemia, indicating a role for IR in white adipose tissue (WAT) homeostasis. In WAT, BD produces IR and an oxidative and energetic imbalance, triggering an intense lipolysis where the serum lipid profile is altered and free fatty acids are increased, consistent with liver lipid accumulation and steatosis. BD exposure heightens inflammation in WAT, elevating pro-inflammatory and reducing anti-inflammatory adipokines, favouring cardiovascular damage. This research provides a comprehensive view of how adolescent BD in rats impacts liver, WAT and pancreas homeostasis, posing a risk for future cardiometabolic complications in adulthood.Artículo Adipose-derived stem cells decreased microglia activation and protected dopaminergic loss in rat lipopolysaccharide model(John Wiley & Sons, 2019-08) Muñoz Pinto, Mario Faustino; Argüelles Castilla, Sandro; Medina, Rafael; Cano Rodríguez, María Mercedes; Ayala Gómez, Antonio; Universidad de Sevilla. Departamento de Fisiología; Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular; Junta de AndalucíaAdult stem cell therapy is being used extensively to rejuvenate damaged tissue. One important tissue source to obtain these cells is adipose, which contains cells called adipose-derived stem cells (ADSCs). These cells have a great therapeutic potential not only for their multipotent properties as well as for immunomodulatory effects on the immune system. Parkinson's disease is characterized as neurodegenerative disorder which etiology is undoubtedly related to neuroinflammation process. The properties of ADSCs can be used as a new tool in stem cells therapy to treat neurodegenerative disorders. However, their efficacies are still controversial. Some authors have reported neuroprotection effects, while others did not find differences or stem cells increased the damage. Our previous study showed that ADSCs can survive long time after transplantation, suggesting us some biological effects could need more time to be repaired. In this study, we assessed the neuroprotection 6 months after transplantation. Our results suggest ADSCs can protect the dopaminergic loss after lipopolysaccharide (LPS) injection both reducing the microglia activation and differentiating into dopaminergic cells.Artículo Advantages and Disadvantages of Apoptosis in the Aging Process(Wiley-Blackwell, 2019) Argüelles Castilla, Sandro; Guerrero Castilla, Angélica; Cano Rodríguez, María Mercedes; Muñoz Pinto, Mario Faustino; Ayala Gómez, Antonio; Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular; Universidad de Sevilla. Departamento de Fisiología; Universidad de SevillaResearchers cannot predict as yet how long a human being can live. Life expectancy has been steadily increasing in the last century, but perhaps not always the quality of life in parallel with it. Future generations will be faced with the problems of an increased life expectancy along with the emergence of new age-related diseases. A deeper understanding of the aging process is crucial to ameliorate, if not to prevent, these projected new old-age diseases. One of the mechanisms responsible for healthy aging is through the effective maintenance of physiological, biochemical, and immunological functions. To carry this out, the organism needs to create new cells to replace old ones and to induce the disappearance of old and damaged cells. Apoptosis is involved in all these processes. However, if apoptosis is dysregulated, premature senescence-associated diseases are likely to appear. In our review, the focus will be on a better understanding of the role of apoptosis in the aging process. These signaling pathways will most assuredly be pharmacologically targeted in antiaging medicine therapies.Artículo Afferent and Efferent Connections of the Mesencephalic Reticular Formation in Goldfish(Elsevier, 2008) Luque Laó, María Ángeles; Pérez Pérez, M. P.; Herrero Rama, Luis Jacinto; Torres Ruiz, Blas; Universidad de Sevilla. Departamento de Fisiología; Ministerio de Educación y Cultura (MEC). EspañaThe physiology of the mesencephalic reticular formation (MRF) in goldfish suggests its contribution to eye and body movements, but the afferent and efferent connections underlying such movements have not been determined. Therefore, we injected the bidirectional tracer biotinylated dextran amine into functionally identified MRF sites. We found retrogradely labelled neurons and anterogradely labelled boutons within nuclei of the following brain regions: (1) the telencephalon: a weak and reciprocal connectivity was confined to the central zone of area dorsalis and ventral nucleus of area ventralis; (2) the diencephalon: reciprocal connections were abundant in the ventral and dorsal thalamic nuclei; the central pretectal nucleus was also reciprocally wired with the MRF, but only boutons were present in the superficial pretectal nucleus; the preoptic and suprachiasmatic nuclei showed abundant neurons and boutons; the MRF was reciprocally connected with the preglomerular complex and the anterior tuberal nucleus; (3) the mesencephalon: neurons and boutons were abundant within deep tectal layers; reciprocal connections were also present within the torus semicircularis and the contralateral MRF; neurons were abundant within the nucleus isthmi; and (4) the rhombencephalon: the superior and middle parts of the reticular formation received strong projections from the MRF, while the projection to the inferior area was weaker; sparse neurons were present throughout the reticular formation; a reciprocal connectivity was observed with the sensory trigeminal nucleus; the medial and magnocellular nuclei of the octaval column projected to the MRF. These results support the participation of the MRF in the orienting response. The MRF could also be involved in other motor tasks triggered by visual, auditory, vestibular, or somatosensory signals.Artículo Age-Dependent Vulnerability to Oxidative Stress of Postnatal Rat Pyramidal Motor Cortex Neurons(MDPI, 2020-12) Carrascal Moreno, María Livia; Gorton, Ella; Pardillo Díaz, Ricardo; Pérez García, Patricia; Gómez Oliva, Ricardo; Nuñez Abades, Pedro Antonio; Universidad de Sevilla. Departamento de Fisiología; Ministerio de Ciencia, Innovación y Universidades (MICINN). España; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Junta de AndalucíaOxidative stress is one of the main proposed mechanisms involved in neuronal degeneration. To evaluate the consequences of oxidative stress on motor cortex pyramidal neurons during postnatal development, rats were classified into three groups: Newborn (P2–P7); infantile (P11–P15); and young adult (P20–P40). Oxidative stress was induced by 10 µM of cumene hydroperoxide (CH) application. In newborn rats, using the whole cell patch-clamp technique in brain slices, no significant modifications in membrane excitability were found. In infantile rats, the input resistance increased and rheobase decreased due to the blockage of GABAergic tonic conductance. Lipid peroxidation induced by CH resulted in a noticeable increase in protein-bound 4-hidroxynonenal in homogenates in only infantile and young adult rat slices. Interestingly, homogenates of newborn rat brain slices showed the highest capacity to respond to oxidative stress by dramatically increasing their glutathione and free thiol content. This increase correlated with a time-dependent increase in the glutathione reductase activity, suggesting a greater buffering capacity of newborn rats to resist oxidative stress. Furthermore, pre-treatment of the slices with glutathione monoethyl ester acted as a neuroprotector in pyramidal neurons of infantile rats. We conclude that during maturation, the vulnerability to oxidative stress in rat motor neurons increases with age.Artículo Aging and Oxidative Stress Decrease Pineal Elongation Factor 2: In Vivo Protective Effect of Melatonin in Young Rats Treated With Cumene Hydroperoxide(Wiley-Blackwell, 2017) Muñoz Pinto, Mario Faustino; Argüelles Castilla, Sandro; Cano Rodríguez, María Mercedes; Marotta, Francesco; Ayala Gómez, Antonio; Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular; Universidad de Sevilla. Departamento de Fisiología; Junta de AndalucíaWe studied the alterations of Elongation Factor 2 (eEF2) in the pineal gland of aged rats as well as the possible protective role of exogenous melatonin on these changes in young rats treated with cumene hydroperoxide (CH), a compound that promotes lipid peroxidation and inhibits protein synthesis. The study was performed using male Wistar rats of 3 (control), 12, and 24 months and 3-month-old rats treated with CH, melatonin, and CH plus melatonin. We found that pineal eEF-2 is affected by aging and CH, these changes being prevented by exogenous melatonin in the case of CH-treated rats. The proteomic studies show that many other proteins are affected by aging and oxidative stress in the pineal gland. The results suggest that one of the possible mechanisms underlying pineal gland dysfunction during aging is the effect of lipid peroxidation on eEF-2, which is a key component of protein synthesis machinery.Artículo Akt/mTOR Role in Human Foetoplacental Vascular Insulin Resistance in Diseases of Pregnancy(Hindawi Publishing Corporation, 2017) Villalobos Labra, Roberto; Silva, Luis Felipe; Subiabre, Mario; Araos, Joaquín; Salsoso Rodríguez, Rocío; Sobrevia Luarte, Luis; Universidad de Sevilla. Departamento de Fisiología; European Union (UE)Insulin resistance is characteristic of pregnancies where the mother shows metabolic alterations, such as preeclampsia (PE) and gestational diabetes mellitus (GDM), or abnormal maternal conditions such as pregestational maternal obesity (PGMO). Insulin signalling includes activation of insulin receptor substrates 1 and 2 (IRS1/2) as well as Src homology 2 domain-containing transforming protein 1, leading to activation of 44 and 42 kDa mitogen-activated protein kinases and protein kinase B/Akt (Akt) signalling cascades in the human foetoplacental vasculature. PE, GDM, and PGMO are abnormal conditions coursing with reduced insulin signalling, but the possibility of the involvement of similar cell signalling mechanisms is not addressed. This review aimed to determine whether reduced insulin signalling in PE, GDM, and PGMO shares a common mechanism in the human foetoplacental vasculature. Insulin resistance in these pathological conditions results from reduced Akt activation mainly due to inhibition of IRS1/2, likely due to the increased activity of the mammalian target of rapamycin (mTOR) resulting from lower activity of adenosine monophosphate kinase. Thus, a defective signalling via Akt/mTOR in response to insulin is a central and common mechanism of insulin resistance in these diseases of pregnancy. In this review, we summarise the cell signalling mechanisms behind the insulin resistance state in PE, GDM, and PGMO focused in the Akt/mTOR signalling pathway in the human foetoplacental endothelium.Artículo Algunas claves ocultas sobre la fiebre(Real e ilustre colegio oficial de farmaceúticos de Sevilla, 2003) Ojeda Murillo, María Luisa; Universidad de Sevilla. Departamento de FisiologíaArtículo Alteraciones fisiológicas en los transtornos de la conducta alimentaria(Real e Ilustre Colegio Oficial de Farmacéuticos de Sevilla, 2022) Benítez Vidal, L.; Cano Rodríguez, María Mercedes; Universidad de Sevilla. Departamento de FisiologíaLos trastornos de la conducta alimentaria (TCA) engloban a una serie de enfermedades men- tales graves que cada vez afectan a más personas. Dentro de este trastorno encontramos varias enferme- dades, pero, todas tienen en común que presentan una alteración en la conducta alimentaria. Las más importantes son anorexia nerviosa, bulimia nerviosa y trastorno por atracón. Los TCA se consideran trastornos multifactoriales puesto que están implicados numerosos factores en su aparición como fac- tores socioculturales, biológicos, neuroendocrinológicos y psicológicos. Además, aunque son trastornos que pueden aparecer en cualquier persona independientemente de la edad o el sexo, es de destacar que son más frecuentes en mujeres jóvenes. La anorexia se caracteriza por un terror al aumento del peso y una imagen distorsionada de la figura corporal lo que lleva a que realicen dietas muy estrictas. Por su parte, la bulimia se caracteriza por la presencia de atracones y, posteriormente, conductas compensato- rias para evitar el aumento del peso corporal. Por último, el trastorno por atracón es similar a la bulimia nerviosa, ya que aparecen los atracones característicos, pero no se realizan conductas compensatorias para evitar el aumento del peso corporal. El objetivo del presente trabajo fue realizar una revisión bi- bliográfica sobre estas patologías y sus consecuencias fisiológicas. Estos comportamientos específicos conllevan la aparición de múltiples complicaciones médicas que acaban afectando al funcionamiento de distintos sistemas fisiológicos, así como a la actividad psicosocial del paciente e incluso pueden llevar a la muerte. La anorexia es la que presenta consecuencias más graves, de las cuales, las más importantes desde el punto de vista de la peligrosidad son las óseas, cardiovasculares y endocrinas. Por otro lado, en la bulimia las complicaciones más frecuentes son las del tracto digestivo debido a las conductas purgati- vas y, por último, en el trastorno por atracón la complicación más frecuente es la obesidad.