GABAergic Projections to the Oculomotor Nucleus in the Goldfish (carassius Auratus)

The mammalian oculomotor nucleus receives a strong γ-aminobutyric acid (GABA)ergic synaptic input, whereas such projections have rarely been reported in fish. In order to determine whether this synaptic organization is preserved across vertebrates, we investigated the GABAergic projections to the oculomotor nucleus in the goldfish by combining retrograde transport of biotin dextran amine, injected into the antidromically identified oculomotor nucleus, and GABA immunohistochemistry. The main source of GABAergic afferents to the oculomotor nucleus was the ipsilateral anterior octaval nucleus, with only a few, if any, GABAergic neurons being located in the contralateral tangential and descending nuclei of the octaval column. In mammals there is a nearly GABAergic inhibitory inputs; thus, the vestibulooculomotor GABAergic circuitry follows a plan that appears to be shared throughout the vertebrate phylogeny. The second major source of GABAergic projections was the rhombencephalic reticular formation, primarily from the medial area but, to a lesser extent, from the inferior area. A few GABAergic oculomotor projecting neurons were also observed in the ipsilateral nucleus of the medial longitudinal fasciculus. The GABAergic projections from neurons located in both the reticular formation surrounding the abducens nucleus and the nucleus of the medial reticular formation have primarily been related to the control of saccadic eye movements. Finally, all retrogradely labeled internuclear neurons of the abducens nucleus, and neurons in the cerebellum (close to the caudal lobe), were negative for GABA. These data suggest that the vestibuloocular and saccadic inhibitory GABAergic systems appear early in vertebrate phylogeny to modulate the firing properties of the oculomotor nucleus motoneurons

Age-Dependent Vulnerability to Oxidative Stress of Postnatal Rat Pyramidal Motor Cortex Neurons

Oxidative 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 mu M 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

Vitamin D deficiency as a potential risk factor for accelerated aging, impaired hippocampal neurogenesis and cognitive decline: a role for Wnt/β-catenin signaling

Vitamin D is an essential fat-soluble vitamin that participates in several homeostatic functions in mammalian organisms. Lower levels of vitamin D are produced in the older population, vitamin D deficiency being an accelerating factor for the progression of the aging process. In this review, we focus on the effect that vitamin D exerts in the aged brain paying special attention to the neurogenic process. Neurogenesis occurs in the adult brain in neurogenic regions, such as the dentate gyrus of the hippocampus (DG). This region generates new neurons that participate in cognitive tasks. The neurogenic rate in the DG is reduced in the aged brain because of a reduction in the number of neural stem cells (NSC). Homeostatic mechanisms controlled by the Wnt signaling pathway protect this pool of NSC from being depleted. We discuss in here the crosstalk between Wnt signaling and vitamin D, and hypothesize that hypovitaminosis might cause failure in the control of the neurogenic homeostatic mechanisms in the old brain leading to cognitive impairment. Understanding the relationship between vitamin D, neurogenesis and cognitive performance in the aged brain may facilitate prevention of cognitive decline and it can open a door into new therapeutic fields by perspectives in the elderly.Ministerio de Ciencia, Innovación y Universidades RTI2018-099908-B-C21FEDER-UCA18-1066

Evolution of Experimental Models in the Study of Glioblastoma: Toward Finding Efficient Treatments

Glioblastoma (GBM) is the most common form of brain tumor characterized by its resistance to conventional therapies, including temozolomide, the most widely used chemotherapeutic agent in the treatment of GBM. Within the tumor, the presence of glioma stem cells (GSC) seems to be the reason for drug resistance. The discovery of GSC has boosted the search for new experimental models to study GBM, which allow the development of new GBM treatments targeting these cells. In here, we describe different strategies currently in use to study GBM. Initial GBM investigations were focused in the development of xenograft assays. Thereafter, techniques advanced to dissociate tumor cells into single-cell suspensions, which generate aggregates referred to as neurospheres, thus facilitating their selective expansion. Concomitantly, the finding of genes involved in the initiation and progression of GBM tumors, led to the generation of mice models for the GBM. The latest advances have been the use of GBM organoids or 3D-bioprinted mini-brains. 3D bio-printing mimics tissue cytoarchitecture by combining different types of cells interacting with each other and with extracellular matrix components. These in vivo models faithfully replicate human diseases in which the effect of new drugs can easily be tested. Based on recent data from human glioblastoma, this review critically evaluates the different experimental models used in the study of GB, including cell cultures, mouse models, brain organoids, and 3D bioprinting focusing in the advantages and disadvantages of each approach to understand the mechanisms involved in the progression and treatment response of this devastating disease

Effects of classical PKC activation on hippocampal neurogenesis and cognitive performance: mechanism of action

Hippocampal neurogenesis has widely been linked to memory and learning performance. New neurons generated from neural stem cells (NSC) within the dentate gyrus of the hippocampus (DG) integrate in hippocampal circuitry participating in memory tasks. Several neurological and neuropsychiatric disorders show cognitive impairment together with a reduction in DG neurogenesis. Growth factors secreted within the DG promote neurogenesis. Protein kinases of the protein kinase C (PKC) family facilitate the release of several of these growth factors, highlighting the role of PKC isozymes as key target molecules for the development of drugs that induce hippocampal neurogenesis. PKC activating diterpenes have been shown to facilitate NSC proliferation in neurogenic niches when injected intracerebroventricularly. We show in here that long-term administration of diterpene ER272 promotes neurogenesis in the subventricular zone and in the DG of mice, affecting neuroblasts differentiation and neuronal maturation. A concomitant improvement in learning and spatial memory tasks performance can be observed. Insights into the mechanism of action reveal that this compound facilitates classical PKCα activation and promotes transforming growth factor alpha (TGFα) and, to a lesser extent, neuregulin release. Our results highlight the role of this molecule in the development of pharmacological drugs to treat neurological and neuropsychiatric disorders associated with memory loss and a deficient neurogenesis.Ministerio de Ciencia, Innovación y Universidades de España (MICINN) RTI-2018-099908-B-C21 y RTI-2018-099908-B-C22Ministerio de Ciencia, Innovación y Universidades de España y Fondos FEDER de la Unión Europea (MICINN/FEDER) BFU2016-75038RConsejería de Economía, Conocimiento, Empresas y Universidades de la Junta de Andalucía y Fondos FEDER. FEDER-UCA18-10664

Effects of classical PKC activation on hippocampal neurogenesis and cognitive performance: mechanism of action

Hippocampal neurogenesis has widely been linked to memory and learning performance. New neurons generated from neural stem cells (NSC) within the dentate gyrus of the hippocampus (DG) integrate in hippocampal circuitry participating in memory tasks. Several neurological and neuropsychiatric disorders show cognitive impairment together with a reduction in DG neurogenesis. Growth factors secreted within the DG promote neurogenesis. Protein kinases of the protein kinase C (PKC) family facilitate the release of several of these growth factors, highlighting the role of PKC isozymes as key target molecules for the development of drugs that induce hippocampal neurogenesis. PKC activating diterpenes have been shown to facilitate NSC proliferation in neurogenic niches when injected intracerebroventricularly. We show in here that long-term administration of diterpene ER272 promotes neurogenesis in the subventricular zone and in the DG of mice, affecting neuroblasts differentiation and neuronal maturation. A concomitant improvement in learning and spatial memory tasks performance can be observed. Insights into the mechanism of action reveal that this compound facilitates classical PKC alpha activation and promotes transforming growth factor alpha (TGF alpha) and, to a lesser extent, neuregulin release. Our results highlight the role of this molecule in the development of pharmacological drugs to treat neurological and neuropsychiatric disorders associated with memory loss and a deficient neurogenesis

Diminution of Voltage Threshold Plays a Key Role in Determining Recruitment of Oculomotor Nucleus Motoneurons during Postnatal Development

The size principle dictates the orderly recruitment of motoneurons (Mns). This principle assumes that Mns of different sizes have a similar voltage threshold, cell size being the crucial property in determining neuronal recruitment. Thus, smaller neurons have higher membrane resistance and require a lower depolarizing current to reach spike threshold. However, the cell size contribution to recruitment in Mns during postnatal development remains unknown. To investigate this subject, rat oculomotor nucleus Mns were intracellularly labeled and their electrophysiological properties recorded in a brain slice preparation. Mns were divided into 2 age groups: neonatal (1–7 postnatal days, n = 14) and adult (20–30 postnatal days, n = 10). The increase in size of Mns led to a decrease in input resistance with a strong linear relationship in both age groups. A well-fitted inverse correlation was also found between input resistance and rheobase in both age groups. However, input resistance versus rheobase did not correlate when data from neonatal and adult Mns were combined in a single group. This lack of correlation is due to the fact that decrease in input resistance of developing Mns did not lead to an increase in rheobase. Indeed, a diminution in rheobase was found, and it was accompanied by an unexpected decrease in voltage threshold. Additionally, the decrease in rheobase co-varied with decrease in voltage threshold in developing Mns. These data support that the size principle governs the recruitment order in neonatal Mns and is maintained in adult Mns of the oculomotor nucleus; but during postnatal development the crucial property in determining recruitment order in these Mns was not the modifications of cell size-input resistance but of voltage threshold

El uso de una escape room como recurso docente en la Facultad de Farmacia

[EN] Escape Rooms are educational resources that are being used by many educators, fostering elements of collaboration that help in social skills development. In this study, a multidisciplinary Escape Room has been developed as an educational tool in order to improve students learning and prepare them for the future of professional practice. 145 students and 12 professors belonging to 8 different areas of knowledge from the Faculty of Pharmacy of the University of Seville participated in this activity. Through this innovation, a student-teacher feedback has been created, improving their relationship and learning from each other. The results obtained through satisfaction surveys show the great acceptance that the escape room had among the students, being the study valued with an overall score of 4.83/5. Although 93% of the students considered the activity of high/very high difficulty, 100% of them emphasize that this tool encourages teamwork and 86.9% consider that it reinforces knowledge. This study has awakened students motivation and interest in the subjects involved, strengthening learning and knowledge of the fundamental concepts acquired, and promoting teamwork and problem solving.[ES] Las Escape Rooms son un tipo de recurso que está siendo utilizado por muchos educadores, propiciando elementos de colaboración que ayudan a desarrollar habilidades sociales. En este estudio se ha desarrollado una Escape Room multidisciplinar como herramienta educativa con el fin de mejorar el aprendizaje de los estudiantes y prepararlos para el futuro de la práctica profesional. Participaron 145 alumnos y 12 profesores adscritos a 8 áreas de conocimiento distintas de la Facultad de Farmacia de la Universidad de Sevilla. Mediante esta innovación se ha producido una retroalimentación alumno-profesor, mejorando su relación y aprendiendo mutuamente. Los resultados obtenidos mediante encuestas de satisfacción muestran la gran aceptación que ha tenido la Escape Room entre los alumnos, siendo el estudio valorado con una puntuación general de 4,83/5. A pesar de que el 93% de los alumnos consideró la actividad de alta/muy alta dificultad, el 100% de los mismos destacan que esta herramienta fomenta el trabajo en equipo y el 86,9% considera que refuerza los conocimientos. Este estudio ha despertado en los alumnos la motivación e interés por las asignaturas implicadas, fortaleciendo el aprendizaje y conocimiento de los conceptos fundamentales adquiridos, y propiciando el trabajo en equipo y la resolución de problemas.Gutiérrez Praena, D.; Rios -Reina, R.; Ruiz, R.; Talero, E.; Callejón, R.; Callejón, RM.; Casas, M.... (2019). El uso de una escape room como recurso docente en la Facultad de Farmacia. En IN-RED 2019. V Congreso de Innovación Educativa y Docencia en Red. Editorial Universitat Politècnica de València. 1145-1155. https://doi.org/10.4995/INRED2019.2019.10356OCS1145115

Instagram como herramienta de aprendizaje en Fisiología: @fisiofarma_us

Las redes sociales (RR.SS.) forman parte de nuestra vida diaria convirtiéndose en una de las principales vías de comunicación y búsqueda de información, especialmente entre los más jóvenes. Entre los usuarios que usan de las RR.SS., un gran número son estudiantes universitarios; y entre los temas más tratados se encuentran aquellos relativos a temáticas de ciencias de la salud. Es por ello por lo que desde el Departamento de Fisiología de la Facultad de Farmacia de la Universidad de Sevilla se desarrolló un proyecto de innovación docente durante el curso 2021-2022 cuyo objetivo era la utilización de las RR.SS. para el aprendizaje de las materias impartidas en nuestro departamento, analizando los posibles beneficios derivado del uso de esta por parte de nuestros estudiantes y profesores. Esta actividad consistió en el desarrollo de contenido divulgativo relativo a la Fisiología por parte de estudiantes del Grado en Farmacia, Grado en Óptica-optometría y Doble Grado en ambos, de nuestro Centro para posteriormente ser publicado en una cuenta de Instagram creada para tal fin (@fisiofarma_us). La opinión tanto de los estudiantes como del profesorado sobre el proyecto fue recogida a través de la encuesta al finalizar el proyecto, y se realizó un registro del impacto en la RR.SS. (seguidores, interacciones, etc). Nuestra cuenta Instagram tuvo un gran impacto en RR.SS. Entre los resultados a destacar, los estudiantes consideran que esta actividad ha favorecido su interés por la Fisiología y tanto estudiantes como profesores creen que esta actividad favoreció diferentes herramientas de aprendizaje. Estos resultados nos hacen concluir que el uso adecuado de las RR.SS. puede ser un método efectivo de aprendizaje e incentivo para fomentar una mejor compresión de las asignaturas de Fisiología en grados universitarios de ciencias de la salud, como Farmacia u Óptica-optometría.: Social networks (RR.SS.) have become an integral part of our daily lives and serve as one of the primary means of communication and information retrieval, particularly among younger. A significant proportion of RR.SS. users are university students, and health science topics are among the most frequently discussed subjects. Considering this, the Department of Physiology at the Facultyof Pharmacy at the University of Seville initiated a teaching innovation project during the 2021-2022 academic year. This project aimed to use RR.SS. as a tool for learning the subjects taught within our department and to analyse the potential benefits that could be derived from its use by our students and members of the physiology department. This initiative involved the creation of informative content related to Physiology by students enrolled in the Degree in Pharmacy, Degree in OpticsOptometry, and Double Degree programs at our faculty. This content was subsequently published on an Instagram account created explicitly for this purpose (@fisiofarma_us). At the end of the project, feedback was obtained from both students and professors of the physiology department via a survey, and data about the impact of our initiative on RR.SS. (e.g., number of followers, interactions, and others) was recorded. Our Instagram account generated considerable interest on RR.SS. Notably, students reported that this activity increased their stake in Physiology, and both students and faculty members indicated that it facilitated the use of various learning tools. Based on these findings, we conclude that the use of RR.SS. can effectively enhance learning and promote a deeper understanding of Physiology-related subjects among students enrolled in university-level health science programs such as Pharmacy or Optics-Optometr