Role for neonatal D-serine signaling: prevention of physiological and behavioral deficits in adult Pick1 knockout mice

NMDA glutamate receptors play key roles in brain development, function, and dysfunction. Regulatory roles of D-serine in NMDA receptor-mediated synaptic plasticity have been reported. Nonetheless, it is unclear whether and how neonatal deficits in NMDA-receptor-mediated neurotransmission affect adult brain functions and behavior. Likewise, the role of D-serine during development remains elusive. Here we report behavioral and electrophysiological deficits associated with the frontal cortex in Pick1 knockout mice, which show D-serine deficits in a neonatal and forebrain specific manner. The pathological manifestations observed in adult Pick1 mice are rescued by transient neonatal supplementation of D-serine, but not by a similar treatment in adulthood. These results indicate a role for D-serine in neurodevelopment and provide novel insights on how we interpret data of psychiatric genetics, indicating the involvement of genes associated with D-serine synthesis and degradation, as well as how we consider animal models with neonatal application of NMDA receptor antagonist

Evaluating long-latency auditory evoked potentials in the diagnosis of cortical hearing loss in children

In centrally related hearing loss, there is no apparent damage in the auditory system, but the patient is unable to hear sounds. In patients with cortical hearing loss (and in the absence of communication deficit, either total or partial, as in agnosia or aphasia), some attention-related or language-based disorders may lead to a wrong diagnosis of hearing impairment. The authors present two patients (8 and 11 years old) with no anatomical damage to the ear, the absence of neurological damage or trauma, but immature cortical auditory evoked potentials. Both patients presented a clinical history of multiple diagnoses over several years. Because the most visible symptom was moderate hearing loss, the patients were recurrently referred to audiological testing, with no improvement. This report describes the use of long-latency evoked potentials to determine cases of cortical hearing loss, where hearing impairment is a consequence of underdevelopment at the central nervous systemEspaña, Ministerio de Economía y Competitividad FFI2010-1820

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

Phorbol Diesters and 12-Deoxy-16-hydroxyphorbol 13,16-Diesters Induce TGFα Release and Adult Mouse Neurogenesis

A small library of phorbol 12,13-diesters bearing low lipophilicity ester chains was prepared as potential neurogenic agents in the adult brain. They were also used in a targeted UHPLC–HRMS screening of the latex of Euphorbia resinifera. Two new 12-deoxy-16-hydroxyphorbol 13,16-diesters were isolated, and their structures were deduced using two-dimensional NMR spectroscopy and NOE experiments. The ability of natural and synthetic compounds to stimulate transforming growth factor alpha (TFGα) release, to increase neural progenitor cell proliferation, and to stimulate neurogenesis was evaluated. All compounds that facilitated TGFα release promoted neural progenitor cell proliferation. The presence of two acyloxy moieties on the tigliane skeleton led to higher levels of activity, which decreased when a free hydroxyl group was at C-12. Remarkably, the compound bearing isobutyryloxy groups was the most potent on the TGFα assay and at inducing neural progenitor cell proliferation in vitro, also leading to enhanced neurogenesis in vivo when administered intranasally to mice.Ministerio de Ciencia, Innovación y Universidades de España y fondos FEDER. RTI2018–099908-B-C21 y RTI2018–099908-B-C2

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

Acute Colon Inflammation Triggers Primary Motor Cortex Glial Activation, Neuroinflammation, Neuronal Hyperexcitability, and Motor Coordination Deficits

Neuroinflammation 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.Ministerio de Ciencia e Innovación 18.06.07.3005 PID2019-105632RB-I00, Grant RTI-2018.099908-B-C21Agencia Estatal de Investigación AEI/10.13039/50110001103

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

Organización neuronal del grupo respiratorio ventral en la rata

El presente trabajo de investigación pretende establecer un mejor conocimiento de la organización neuronal del GRV en la rata. Esta información es hoy necesaria para los estudios neurofarmacológicos y electrofisológicos (tanto en preparaciones in vivo como in vitro) que se realicen en la rata, como modelo experimental alternativo al gato. Por ello se han cubierto los siguientes objetivos experimentales: 1. Identificación de los distintos tipos neuronales que constituyen el núcleo ambiguo. 2. Identificación de los distintos tipos neuronales del Grupo Respiratorio Ventral. 3. Caracterización de las aferencias (simples y bilaterales) a las principales subdivisiones del Grupo Respiratorio Ventral. 4. Caracterización de las aferencias (simples y bilaterales) del Grupo Respiratorio Ventral a la médula espinal cervical

Estudio del método de evaluación en la asignatura de fisiología animal

Se ha realizado un estudio de las calificaciones obtenidas por los alumnos de la asignatura de Fisiología Animal, en base a diferentes tests de evaluación. Las calificaciones obtenidas por los alumnos fueron extremadamente diferentes (p<O,OOJ) según cada uno de los tres tipos de tests (elección múltiple, problemas y preguntas de desarrollo). Las calificaciones fueron superiores en los exámenes de preguntas de elección múltiple (mediana en el notable) . Las preguntas de desarrollo obtuvieron una calificación menor que los otros dos tipos de tests. La conclusión principal es que una evaluación correcta de los conocimientos no deberá basarse en un solo tipo de prueba. Se propone, por tanto, que el peso de la nota final de Fisiología Animal (teoría) debe provenir en un 50% de un examen de preguntas de elección múltiple y en un 50% de preguntas de preguntas de desarrollo, para conseguir el objetivo de una calificación correcta de los conocimientos.In the present work it has been studied the grades obtained by the students in the course of Animal Physiology, based into three different evaluation tests (multiple election questionnaire, problems, and free writing questions). The obtained grades ofthe students were statistically different (p<O.OOJ) in each one ofthe three different tests. The highest grades were obtained in the multiple election questionnaire (average ofB). The free writing questions obtained the lowest qualification, respect to the other two types oftest. The main conclusion was that a trustworthy evaluation ofthe knowledge should never be based in a unique type oftest. We propase, in this case, that the final grade of Animal Physiology (theory) must be provided by a 50% ofmultiple election questionnaire anda 50% offree writing questions, to obtain a trustworthy evaluation

Utilización del refuerzo positivo como herramienta para la mejora del aprendizaje en la asignatura de Fisiología Celular

Este trabajo describe la actividad docente desarrollada por los profesores de la asignatura de Fisiología Celular de la Facultad de Farmacia, durante el Curso Académico 1997-98, coincidiendo con la implantación del Nuevo Plan de Estudios de la Licenciatura de Farmacia. El desarrollo de la aplicación de la actividad tuvo como objetivo aplicar nuevas estrategias de enseñanza que mejora­sen a) el nivel de participación y motivación de los alumnos en la asignatura a lo largo del curso académico y b) las calificaciones obtenidas por los alumnos. Así mismo, pretendíamos evaluar el proceso de aprendizaje.This work describes the Activity of Teaching Innovation developed by the professors of the subject Cellular Physiology, of the Faculty of Pharmacy, University of Seville, coinciding with the onset of thc New Plan of Studies of Pharmacy, during the academic course 1997-1998. The aim of thc activity was to apply new strategies in teaching to improve: a) the leve! of participation and motivation of the students in the subject throughout the academic course and b) the score obtained by the students. Furthermore, we tried to evaluate the leaming process