RESUMEN
The mechanisms underlying regeneration of the central nervous system (CNS) following lesions have been studied extensively in both vertebrate and invertebrate models. To shed light on regeneration, ascidians, a sister group of vertebrates and with remarkable ability to regenerate their brains, constitute an appropriate model system. Glial cells have been implicated in regeneration in vertebrates; however, their role in the adult ascidian CNS regeneration is unknown. A model of degeneration and regeneration using the neurotoxin 3-acetylpyridine (3AP) in the brain of the ascidian Styela plicata was used to identify astrocyte-like cells and investigate their role. We studied the CNS of control ascidians (injected with artificial sea water) and of ascidians whose CNS was regenerating (1 and 10 days after the injection with 3AP). Our results show that the mRNA of the ortholog of glutamine synthetase (GS), a glial-cell marker in vertebrates, is increased during the early stages of regeneration. Confirming the identity of GS, the protein was identified via immunostaining in a cell population during the same regeneration stage. Last, a single ortholog of GS (GSII) is present in ascidian and amphioxus genomes, while two types exist in fungi, some invertebrates, and vertebrates, suggesting that ascidians have lost the GSI type. Taken together, our findings revealed that a cell population expressing glial-cell markers may play a role in regeneration in adult ascidians. This is the first report of astrocyte-like cells in the adult ascidian CNS, and contributes to understanding of the evolution of glial cells among metazoans.
Asunto(s)
Astrocitos , Sistema Nervioso Central , Glutamato-Amoníaco Ligasa , Urocordados , Animales , Urocordados/fisiología , Sistema Nervioso Central/citología , Sistema Nervioso Central/fisiología , Astrocitos/fisiología , Astrocitos/metabolismo , Astrocitos/citología , Glutamato-Amoníaco Ligasa/metabolismo , Regeneración Nerviosa/fisiologíaRESUMEN
Esta revisión busca proporcionar a los profesionales de la salud una mayor comprensión del dolor para su actividad clínica-asistencial. Basados en la hipóte-sis de neuroplasticidad presentada inicialmente por Ramón y Cajal y la teoría de la compuerta en la vía dolorosa presentada por Melzack y Wall, se ha ela-borado una revisión bibliográfica con el objetivo de abordar la modulación de la vía nociceptiva desde un punto de vista fisiopatológico. Asimismo, se presen-tan los principales resultados obtenidos durante los últimos años en nuestro laboratorio usando ratas Wistar hembras como modelo de dolor experimental. Finalmente, se describe un circuito original de modu-lación central a nivel del subnúcleo caudal del trigé-mino con una visión integral de los componentes del sistema nociceptivo orofacial, para ayudar al clínico a comprender situaciones de sensibilización central con perpetuación del dolor y cómo paulatinamente el sistema nervioso central pone en marcha un sistema de modulación para adaptarse y alcanzar un estado similar al basal (AU)
This review aims to provide health professionals with a better understanding of pain for their clinical-care activity. Based on the neuroplasticity hypothesis initially presented by Ramón and Cajal, and the gate theory in the pain pathway presented by Melzack and Wall, a literature review has been carried out with the aim of addressing the modulation of the nociceptive pathway from a pathophysiological point of view. The main results obtained in recent years in our laboratory using female Wistar rats as an experimental pain model are also presented. Finally, an original central modulation circuit at the level of the caudal trigeminal subnucleus is described with a comprehensive view of the components of the orofacial nociceptive system, to help the clinician to understand situations of central sensitization with perpetuation of pain and how the central nervous system gradually sets in motion a modulation system to adapt and reach a state similar to the basal one (AU)
Asunto(s)
Humanos , Animales , Ratas , Dolor/fisiopatología , Sistema Nervioso Central/fisiología , Nocicepción/fisiología , Plasticidad Neuronal/fisiología , Astrocitos , Ratas Wistar , Hiperalgesia/fisiopatología , InterneuronasRESUMEN
The pineal melatonin (N-acetyl-5-methoxytryptamine) is a molecule associated in a way or another with probably all physiological systems, aiming to fulfil its functional integrative roles in central nervous system activity, sleep and wakefulness cycles, energy metabolism and thermoregulation, immune, reproductive, endocrine, cardiovascular, respiratory and excretory systems. Within this context, the present study aimed to assess in silico the formation of complexes between ligand melatonin and other potential receptor proteins by molecular docking analyses. The main steps established in this experimental procedure were: a) search and selection of the 3D structure of the melatonin from DrugBank; b) search and selection of 3D structures of other target receptor proteins using STRING, protein BLAST and database PDB; and c) formation of the complexes between melatonin and receptors selected using AutoDock4.0 server by molecular docking analyses. High reliability score and significant similarity were only identified between type 1B melatonin and alpha-2A adrenergic receptor. Thus, molecular docking assays were carried out using ligand melatonin and crystallographic structures of the alpha-2A adrenergic receptor coupled to an antagonist (ID PDB 6kux) and a partial agonist (ID PDB 6kuy) available in the database PDB. Binding energy values of -6.79 and -6.98 kcal/mol and structural stability by non-covalent intermolecular interactions were predicted during the formation of complexes between melatonin and alpha-2A adrenergic receptor 6kux and 6kuy, respectively. In this way, the findings described in current study may indicate strong interactions between melatonin and adrenoceptors, suggesting its possible partial agonist effect on the activation of the alfa-2A adrenergic receptor.(AU)
A melatonina pineal (N-acetil-5-metoxitriptamina) é uma molécula associada de um modo ou outro com provavelmente todos os sistemas fisiológicos, visando cumprir seus papéis funcionais integradores na atividade do sistema nervoso central, ciclos de sono e vigília, metabolismo energético e termorregulação, sistemas imunológico, reprodutivo, endócrino, cardiovascular, respiratório e excretor. Assim, o presente estudo objetivou avaliar in silico a formação de complexos entre o ligante melatonina e outras proteínas potenciais receptoras por meio de análises de docagem molecular. As principais etapas estabelecidas neste procedimento experimental foram: a) busca e seleção da estrutura 3D da melatonina a partir do banco de dados DrugBank; b) busca e seleção de estruturas 3D de outras proteínas receptoras-alvo utilizando STRING, proteína BLAST e o banco de dados PDB; e c) avaliação da formação dos complexos entre melatonina e receptores selecionados a partir do servidor AutoDock4.0 para análises de docagem molecular. Alto escore de confiabilidade e similaridade significativa foram identificados apenas entre a melatonina do tipo 1B e o receptor alfa-2A adrenérgico. Valores de energia de ligação de -6,79 e -6,98 kcal/mol e estabilidade estrutural pela presença de interações intermoleculares não covalentes foram preditos durante a formação de complexos entre o ligante melatonina e os receptores adrenérgico alfa-2A 6kux e 6kuy, respectivamente. Dessa forma, os achados descritos no presente estudo podem indicar fortes interações entre melatonina e adrenoceptores, sugerindo seu possível efeito agonista parcial na ativação do receptor alfa-2A adrenérgico.(AU)
Asunto(s)
Humanos , Sueño , Vigilia , Sistema Nervioso Central/fisiología , Melatonina/fisiología , Simulación del Acoplamiento MolecularRESUMEN
Caffeine is one of the most consumed ergogenic aids around the world. Many studies support the ergogenic effect of caffeine over a large spectrum of exercise types. While the stimulatory effect of caffeine on the central nervous system is the well-accepted mechanism explaining improvements in exercise performance during high-intensity whole-body exercise, in which other physiological systems such as pulmonary, cardiovascular, and muscular systems are maximally activated, a direct effect of caffeine on such systems cannot be ignored. A better understanding of the effects of caffeine on multiple physiological systems during high-intensity whole-body exercise might help to expand its use in different sporting contexts (e.g., competitions in different environments, such as altitude) or even assist the treatment of some diseases (e.g., chronic obstructive pulmonary disease). In the present narrative review, we explore the potential effects of caffeine on the pulmonary, cardiovascular, and muscular systems, and describe how such alterations may interact and thus contribute to the ergogenic effects of caffeine during high-intensity whole-body exercise. This integrative approach provides insights regarding how caffeine influences endurance performance and may drive further studies exploring its mechanisms of action in a broader perspective.
Asunto(s)
Cafeína/farmacología , Fenómenos Fisiológicos Cardiovasculares/efectos de los fármacos , Sistema Nervioso Central/efectos de los fármacos , Ejercicio Físico/fisiología , Pulmón/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Sustancias para Mejorar el Rendimiento/farmacología , Resistencia Física/efectos de los fármacos , Animales , Sistema Nervioso Central/fisiología , Humanos , Pulmón/fisiología , Músculo Esquelético/fisiologíaRESUMEN
The concept of central nervous system (CNS) inflammation has evolved over the last decades. Neuroinflammation is the response of reactive CNS components to altered homeostasis, regardless of the cause to be endogenous or exogenous. Neurological diseases, whether traumatic, neoplastic, ischemic, metabolic, toxic, infectious, autoimmune, developmental, or degenerative, involve direct and indirect immune-related neuroinflammation. Brain infiltrates of the innate and adaptive immune system cells appear in response to an infective or otherwise noxious agent and produce inflammatory mediators. Mediators of inflammation include local and recruited cells and signals. Processes derived from extrinsic and intrinsic CNS diseases also elicit the CNS inflammatory response. A deeper understanding of immune-related inflammation in health and disease is necessary to find potential therapeutic targets for preventing or reducing CNS damage. This review is aimed at discussing the innate and adaptive immune system functions and their roles in regulating brain cell responses in disease and homeostasis maintenance.
Asunto(s)
Enfermedades del Sistema Nervioso Central/diagnóstico , Enfermedades del Sistema Nervioso Central/terapia , Sistema Nervioso Central/fisiología , Neuroinmunomodulación , Enfermedades Neuroinflamatorias/diagnóstico , Enfermedades Neuroinflamatorias/terapia , Inmunidad Adaptativa , Animales , Astrocitos/metabolismo , Autofagia , Encéfalo/metabolismo , Sistema Nervioso Central/metabolismo , Fibrosis , Homeostasis , Humanos , Hipoxia , Sistema Inmunológico/metabolismo , Inflamación , Mediadores de Inflamación/metabolismo , Microglía/metabolismo , Estrés OxidativoRESUMEN
RESUMEN: La percepción del dolor resulta de múltiples y dinámicos mecanismos en el sistema nervioso central (SNC) y periférico que inhiben o facilitan el estímulo y respuesta nociceptiva. Sin embargo, la principal capacidad de modulación esta a cargo del SNC. Los estímulos nociceptivos son detectados por terminaciones nerviosas libres de neuronas periféricas que sinaptan con neuronas aferentes secundarias de la médula espinal. Luego estas fibras decusan para formar las vías nociceptivas ascendentes. Una vez alcanzadas las estructuras subcorticales, se activan las neuronas del tálamo, quienes envían el estímulo hacia la corteza somatosensorial, desencadenando la percepción consciente del dolor y activando el sistema inhibitorio descendente. Para que la modulación nociceptiva se realice, es necesaria la participación de diversas sustancias o neurotransmisores que conectan áreas del SNC especializadas. Por lo tanto, el objetivo de este estudio fue realizar una revisión de la literatura respecto de los mecanismos que participan en los procesos de modulación central del dolor.
SUMMARY: Pain perception results from multiple and dynamic mechanisms in the central nervous system (CNS) and peripheral nervous system that inhibit or facilitate stimulation and nociceptive response. However, neuromodulation is mainly a function of the CNS. Nociceptive stimulus is detected by peripheral neurons receptors that synapse with the secondary afferent neurons of the spinal cord. These fibers cross to conform the ascending nociceptive pathways. Once the subcortical structures are reached, the thalamus`s neurons are activated; the thalamus send the stimulus to the somatosensory cortex, triggering the conscious perception of pain and activating the descending inhibitory system. For the nociceptive modulation to be carried out, the participation of various substances or neurotransmitters that connect specialized CNS areas is necessary. Therefore, the aim of this study was to review the literature regarding the mechanisms involved in central pain modulation processes.
Asunto(s)
Humanos , Dolor/fisiopatología , Sistema Nervioso Central/fisiología , Percepción del Dolor/fisiología , Dolor Crónico/fisiopatología , Dolor Nociceptivo/fisiopatología , Inhibición Neural , Neuroanatomía , NeurofisiologíaRESUMEN
BACKGROUND: Neurotropic B vitamins play crucial roles as coenzymes and beyond in the nervous system. Particularly vitamin B1 (thiamine), B6 (pyridoxine), and B12 (cobalamin) contribute essentially to the maintenance of a healthy nervous system. Their importance is highlighted by many neurological diseases related to deficiencies in one or more of these vitamins, but they can improve certain neurological conditions even without a (proven) deficiency. AIM: This review focuses on the most important biochemical mechanisms, how they are linked with neurological functions and what deficits arise from malfunctioning of these pathways. DISCUSSION: We discussed the main role of B Vitamins on several functions in the peripheral and central nervous system (PNS and CNS) including cellular energetic processes, antioxidative and neuroprotective effects, and both myelin and neurotransmitter synthesis. We also provide an overview of possible biochemical synergies between thiamine, pyridoxine, and cobalamin and discuss by which major roles each of them may contribute to the synergy and how these functions are inter-related and complement each other. CONCLUSION: Taking into account the current knowledge on the neurotropic vitamins B1, B6, and B12, we conclude that a biochemical synergy becomes apparent in many different pathways in the nervous system, particularly in the PNS as exemplified by their combined use in the treatment of peripheral neuropathy.
Asunto(s)
Fenómenos Fisiológicos del Sistema Nervioso , Piridoxina/fisiología , Tiamina/fisiología , Vitamina B 12/fisiología , Complejo Vitamínico B/fisiología , Animales , Sistema Nervioso Central/fisiología , Humanos , Enfermedades del Sistema Nervioso , Sistema Nervioso Periférico/fisiologíaRESUMEN
OBJECTIVES: To verify the neuromaturational influence in the ability of auditory closure, that is, to verify the performance of children and young adults in the ability of auditory closure, through the time compressed speech test (TCS). METHODS: Thirty children (8 to 10 years old) and 30 young adults (16 to 24 years old) with normal hearing without complaints (neurological, cognitive, auditory processing) who performed TFC (monosyllables and disyllables) with a compression ratio of 60% in both ears. Statistical analysis was performed using analysis of variance (ANOVA) and ANOVA with repeated measures with a significance level of 0.05. The minimum statistical power was 80%. RESULTS: In the comparison between ears, there was no significant difference between groups for the monosyllables. For disyllables, the second ear tested was better in children, and the right ear was better than the left ear for young adults. In the comparison between modalities (monosyllables and disyllables), children did not show significant differences. The performance of the young adults was better in the disyllables in both ears. Comparing the age groups, the young adults were better than the children for both modalities and ears. CONCLUSION: The study has demonstrated the influence and impact of age (maturational factor) on TCS test performance, showing the importance of establishing normality patterns for various age groups to provide a standardized tool for evaluation of auditory closure ability.
Asunto(s)
Vías Auditivas/fisiología , Percepción Auditiva/fisiología , Sistema Nervioso Central/fisiología , Pruebas de Discriminación del Habla/métodos , Adolescente , Factores de Edad , Análisis de Varianza , Niño , Oído/fisiología , Femenino , Lateralidad Funcional/fisiología , Humanos , Masculino , Rendimiento Físico Funcional , Valores de Referencia , Factores de Tiempo , Adulto JovenRESUMEN
The role of diet and gut microbiota in the pathophysiology of neurodegenerative diseases, such as Alzheimer's, has recently come under intense investigation. Studies suggest that human gut microbiota may contribute to the modulation of several neurochemical and neurometabolic pathways, through complex systems that interact and interconnect with the central nervous system. The brain and intestine form a bidirectional communication axis, or vice versa, they form an axis through bi-directional communication between endocrine and complex immune systems, involving neurotransmitters and hormones. Above all, studies suggest that dysbiotic and poorly diversified microbiota may interfere with the synthesis and secretion of neurotrophic factors, such as brain-derived neurotrophic factor, gammaaminobutyric acid and N-methyl D-Aspartate receptors, widely associated with cognitive decline and dementia. In this context, the present article provides a review of the literature on the role of the gutbrain axis in Alzheimer's disease.
Asunto(s)
Enfermedad de Alzheimer/microbiología , Enfermedad de Alzheimer/patología , Sistema Nervioso Central/fisiología , Microbioma Gastrointestinal/fisiología , Animales , HumanosRESUMEN
Multiple sclerosis is a highly prevalent chronic demyelinating disease of the central nervous system. Remyelination is the major therapeutic goal for this disorder. The lack of detailed knowledge about the cellular and molecular mechanisms involved in myelination restricts the design of effective treatments. A recent study by using [De La Fuente et al. (2017) Cell Reports, 20(8): 1755-1764] by using state-of-the-art techniques, including pericyte-deficient mice in combination with induced demyelination, reveal that pericytes participate in central nervous system regeneration. Strikingly, pericytes presence is essential for oligodendrocyte progenitors differentiation and myelin formation during remyelination in the brain. The emerging knowledge from this research will be important for the treatment of multiple sclerosis.
Asunto(s)
Sistema Nervioso Central/fisiología , Vaina de Mielina/fisiología , Pericitos/citología , Animales , Diferenciación Celular/fisiología , Células Cultivadas , Enfermedades Desmielinizantes/fisiopatología , Ratones , Esclerosis Múltiple/fisiopatología , Regeneración Nerviosa/fisiología , Oligodendroglía/citologíaRESUMEN
OBJECTIVES: To verify the neuromaturational influence in the ability of auditory closure, that is, to verify the performance of children and young adults in the ability of auditory closure, through the time compressed speech test (TCS). METHODS: Thirty children (8 to 10 years old) and 30 young adults (16 to 24 years old) with normal hearing without complaints (neurological, cognitive, auditory processing) who performed TFC (monosyllables and disyllables) with a compression ratio of 60% in both ears. Statistical analysis was performed using analysis of variance (ANOVA) and ANOVA with repeated measures with a significance level of 0.05. The minimum statistical power was 80%. RESULTS: In the comparison between ears, there was no significant difference between groups for the monosyllables. For disyllables, the second ear tested was better in children, and the right ear was better than the left ear for young adults. In the comparison between modalities (monosyllables and disyllables), children did not show significant differences. The performance of the young adults was better in the disyllables in both ears. Comparing the age groups, the young adults were better than the children for both modalities and ears. CONCLUSION: The study has demonstrated the influence and impact of age (maturational factor) on TCS test performance, showing the importance of establishing normality patterns for various age groups to provide a standardized tool for evaluation of auditory closure ability.
Asunto(s)
Humanos , Masculino , Femenino , Niño , Adolescente , Adulto Joven , Vías Auditivas/fisiología , Percepción Auditiva/fisiología , Pruebas de Discriminación del Habla , Sistema Nervioso Central/fisiología , Valores de Referencia , Factores de Tiempo , Análisis de Varianza , Factores de Edad , Oído/fisiología , Rendimiento Físico Funcional , Lateralidad Funcional/fisiologíaRESUMEN
Este artículo se ha propuesto como una revisión de las investigaciones que han surgido en la última década en el campo de la neurociencia, y que se hayan relacionadas con la actividad neurobiológica y funcional de la toma de decisiones por parte del ser humano. Así, ha sido posible identificar y dar cuenta de las estructuras del sistema nervioso central que son claves en la comprensión de los procesos relacionados con la toma de decisiones, y a su vez han permitido establecer el rol de las emociones como influencia determinante en este proceso. De igual forma, las investigaciones han posibilitado conocer cómo se lleva a cabo la actividad de tomar decisiones en el cerebro, las relaciones entre las diversas regiones y cómo las emociones guían el resultado.Además, se ha llegado a destacar dos sistemas que explicarían el proceso de la toma de decisiones, uno asociado a la intuición (sistema práctico), donde se destaca la actividad metabólica de la amígdala cerebral y sus redes neuronales; otro que corresponde al razonamiento (sistema analítico), en el cual resalta la participación de las conexiones neuronales de la porción ventromedial del córtex prefrontal.
This paper has proposedas a review of the researchthat has been appearing in the last decade in the field of neuroscience, and the relationship with the neurobiological and functional activity of the human decision making. Therefore, it has been possible to identify and inform the key structures of the central nervous system in the comprehension of the related processes, and it has allowed to stablish the important influence of the emotion in this process. Also, the research hasallowed to know how the decision-making process has been referred in the brain, the relationship between the different brain regions and the emotion who led the outcome. Thus, there are two systems involved in the decision makingprocess; one related with the intuition (practical system), where the metabolic activity of the cerebral amygdala is remarked with their neural networks, and other related with reasoning (analytical system), in which, is important to note the involvement of the ventromedial portion of the prefrontal cortex.
Este artigo foi proposto como uma revisão das pesquisas que surgiram na última década no campo da neurociência, e que tem sido relacionada à atividade neurobiológica e funcional da tomada de decisão pelo ser humano. Assim, foi possível identificar e explicar as estruturas do sistema nervoso central que são fundamentais na compreensão dos processos relacionados à tomada de decisões e, por sua vez, permitiram estabelecer o papel das emoções como influência determinante nesse processo. Da mesma forma, a pesquisa permitiu saber como é a atividade de tomada de decisão no cérebro, as relações entre diferentes regiões e como as emoções orientam o resultado. Ademais, foram destacados dois sistemas que explicam o processo de tomada de decisão, um associado à intuição (sistema prático), que enfatiza a atividade metabólica da amígdala cerebral e suas redes neurais; outro correspondente ao raciocínio (sistema analítico), no qual as conexões neuronais da porção ventromedial do córtex pré-frontal são destacadas.
Asunto(s)
Humanos , Sistema Nervioso Central/fisiología , Toma de Decisiones/fisiología , Emociones/fisiología , Corteza Prefrontal/fisiología , Intuición/fisiologíaRESUMEN
Thyroid hormones (THs) during pregnancy contribute significantly to cellular differentiation and development in several tissues of the offspring, principally the central nervous system (CNS). TH deficiencies, such as hypothyroidism or hypothyroxinemia, are highly frequent during pregnancy worldwide and known to be detrimental for the development of the fetus. The function of CNS in the offspring gestated under TH deficiency will be irreversible impaired, causing low intellectual quotient, attention deficit, and mental retardation. On the other hand, little is known about the effects of TH deficiency in the offspring immune system, being the prevalent notion that the effects are reversible and only for a while will affect the number of B and T cells. Recent studies have shown that maternal hypothyroidism can altered the function of immune system in the offspring, rendering the female offspring more susceptible to suffer autoimmune-inflammatory diseases, such as experimental autoimmune encephalomyelitis (EAE) and to be more resistant to a bacterial infection. In this article we discuss these recent findings, as well as the possible mechanisms underlying these effects and the potential implications for human health.
Asunto(s)
Sistema Nervioso Central/fisiología , Hijo de Padres Discapacitados , Encefalomielitis Autoinmune Experimental , Hipotiroidismo/inmunología , Factores Sexuales , Hormonas Tiroideas/metabolismo , Animales , Diferenciación Celular , Susceptibilidad a Enfermedades , Femenino , Humanos , Hipotiroidismo/genética , Ratones , Madres , Embarazo , Complicaciones del Embarazo/genética , Hormonas Tiroideas/genéticaRESUMEN
There is a tension between the conception of cognition as a central nervous system (CNS) process and a view of cognition as extending towards the body or the contiguous environment. The centralised conception requires large or complex nervous systems to cope with complex environments. Conversely, the extended conception involves the outsourcing of information processing to the body or environment, thus making fewer demands on the processing power of the CNS. The evolution of extended cognition should be particularly favoured among small, generalist predators such as spiders, and here, we review the literature to evaluate the fit of empirical data with these contrasting models of cognition. Spiders do not seem to be cognitively limited, displaying a large diversity of learning processes, from habituation to contextual learning, including a sense of numerosity. To tease apart the central from the extended cognition, we apply the mutual manipulability criterion, testing the existence of reciprocal causal links between the putative elements of the system. We conclude that the web threads and configurations are integral parts of the cognitive systems. The extension of cognition to the web helps to explain some puzzling features of spider behaviour and seems to promote evolvability within the group, enhancing innovation through cognitive connectivity to variable habitat features. Graded changes in relative brain size could also be explained by outsourcing information processing to environmental features. More generally, niche-constructed structures emerge as prime candidates for extending animal cognition, generating the selective pressures that help to shape the evolving cognitive system.
Asunto(s)
Arañas/fisiología , Animales , Conducta Animal/fisiología , Sistema Nervioso Central/fisiología , Cognición , Aprendizaje/fisiologíaRESUMEN
Over 25 years have passed since peroxisome proliferators-activated receptors (PPARs), were first described. Like other members of the nuclear receptors superfamily, PPARs have been defined as critical sensors and master regulators of cellular metabolism. Recognized as ligand-activated transcription factors, they are involved in lipid, glucose and amino acid metabolism, taking part in different cellular processes, including cellular differentiation and apoptosis, inflammatory modulation and attenuation of acute and chronic neurological damage in vivo and in vitro. Interestingly, PPAR activation can simultaneously reprogram the immune response, stimulate metabolic and mitochondrial functions, promote axonal growth, induce progenitor cells to differentiate into myelinating oligodendrocytes, and improve brain clearance of toxic molecules such as ß-amyloid peptide. Although the molecular mechanisms and cross-talk with different molecular pathways are still the focus of intense research, PPARs are considered potential therapeutic targets for several neuropathological conditions, including degenerative disorders such as Alzheimer's, Parkinson's and Huntington's disease. This review considers recent advances regarding PPARs, as well as new PPAR agonists. We focus on the mechanisms behind the neuroprotective effects exerted by PPARs and summarise the roles of PPARs in different pathologies of the central nervous system, especially those associated with degenerative and inflammatory mechanisms.
Asunto(s)
Sistema Nervioso Central/fisiología , Inflamación/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Receptores Activados del Proliferador del Peroxisoma/metabolismo , Enfermedad de Alzheimer/metabolismo , Animales , Humanos , Enfermedad de Huntington/metabolismo , Enfermedad de Parkinson/metabolismoRESUMEN
The brain performs exceptionally complex and dynamic tasks that depend on the coordinated interaction of neurons, glial cells, endothelial cells, pericytes, smooth muscle cells, ependymal cells, and circulating blood cells. Among these cells, glial cells have emerged as crucial protagonists in the regulation of synaptic transmission and neural function. Indeed, these cells express a wide range of receptors that enable them to sense changes in neuronal activity and the microenvironment by responding locally via the release of bioactive molecules known as gliotransmitters. In the central nervous system (CNS), a novel mechanism that allows gliotransmission via the opening of hemichannels has been proposed. These channels are composed of six protein subunits consisting of connexins or pannexins, which are two highly conserved protein families that are encoded by 21 and 3 genes, respectively, in humans. Typically, glial cell hemichannels exhibit low levels of activity, but this activity is sufficient to ensure the release of a broad spectrum of gliotransmitters, including ATP, D-serine, glutamate, adenosine, and glutathione. Here, we briefly review the current findings regarding the effects of the hemichannel-dependent release of gliotransmitters on the physiology of the CNS.
Asunto(s)
Sistema Nervioso Central/fisiología , Conexina 43/metabolismo , Neuroglía/fisiología , Neurotransmisores/metabolismo , Transmisión Sináptica/fisiología , Animales , Astrocitos/citología , Astrocitos/fisiología , Sistema Nervioso Central/citología , Conexina 43/genética , Conexinas/genética , Conexinas/metabolismo , Uniones Comunicantes/fisiología , Expresión Génica , Humanos , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Neuroglía/citología , Neuronas/citología , Neuronas/fisiología , Neurotransmisores/genética , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Receptores Purinérgicos P2X7/genética , Receptores Purinérgicos P2X7/metabolismo , Sinapsis/fisiologíaRESUMEN
The consumption of marijuana extracted from Cannabis sativa and indica plants involves an important cultural impact in Mexico. Their psychological stimulatory effect is widely recognized; their biochemical and molecular components interact with CB1 and CB2 (endocannabinoid system) receptors in various central nervous system structures (CNS) and immune cells. The psychoactive element Δ-9-tetrahydrocannabinol (THC) can be reproduced synthetically. Systematic reviews show evidence of therapeutic effectiveness of therapeutic marijuana only for certain symptoms of multiple sclerosis (spasticity, spasms and pain), despite attempts for its widespread use, including refractory childhood epilepsy. Evidence indicates significant adverse effects of smoked marijuana on the structure, functioning and brain connectivity. Cannabis exposure during pregnancy affects fetal brain development, potentially leading to later behavioral problems in children. Neuropsychological tests and advanced imaging techniques show involvement in the learning process in adolescents with substance use. Also, marijuana increases the cognitive impairment in patients with multiple sclerosis. Social and ethical consequences to legally free marijuana for recreational use may be deleterious transcendentally. The medicinal or psychoactive cannabinol no addictive effect requires controlled proven efficacy and safety before regulatory approval studies.
El consumo de la mariguana conlleva un importante impacto cultural en México. Su efecto psicológicamente estimulante es ampliamente reconocido, sus componentes bioquímicos y moleculares interactúan con los receptores CB1 y CB2 (sistema endocannabinoide) en diversas estructuras del sistema nervioso central (SNC) y de las células inmunes. El elemento psicoactivo Δ-9-Tetrahidrocannabinol (THC) puede ser reproducido sintéticamente.Revisiones sistemáticas muestran evidencia en efectividad del consumo de mariguana terapéutica solo para ciertos síntomas de esclerosis múltiple (espasticidad, espasmos y dolor), a pesar de los intentos para su uso extenso, incluyendo epilepsias infantiles refractarias. La evidencia señala importantes efectos adversos de la mariguana fumada sobre las estructuras, el funcionamiento y la conectividad cerebral. La exposición al cannabis durante el embarazo afecta el desarrollo cerebral del feto, pudiendo generar problemas conductuales tardíos en los hijos. Pruebas sensitivas neuropsicológicas y avanzadas técnicas imagenológicas demuestran afectación en el proceso de aprendizaje en adolescentes consumidores. Asimismo, la mariguana aumenta el deterioro cognitivo en pacientes con esclerosis múltiple. Las consecuencias sociales y éticas al liberar legalmente mariguana para uso lúdico pueden ser trascendentalmente deletéreas. El cannabinol medicinal sin efecto psicoactivo o adictivo requiere de estudios controlados de eficacia y seguridad comprobadas antes de su aprobación regulatoria.
Asunto(s)
Cannabis/efectos adversos , Sistema Nervioso Central/efectos de los fármacos , Fumar Marihuana/efectos adversos , Marihuana Medicinal/farmacología , Sistema Nervioso Central/fisiología , Características Culturales , Control de Medicamentos y Narcóticos , Humanos , Fumar Marihuana/legislación & jurisprudencia , México , Condiciones SocialesRESUMEN
Potentially neurogenic areas were initially identified by incorporation of bromodeoxyuridine (BrdU) in cells underlying the subventricular zone (SVZ) of the lateral ventricles wall, hippocampus and olfactory bulbs of newborn guinea pigs. Neural precursors from the SVZ were cultured in suspension, generating neurospheres (NSFs), which, upon dissociation were able to generate new NSFs. Upon culture in the absence of growth factors, cells dissociated from NSFs displayed evidence for neural differentiation, giving rise to cells from neural lineage. Flow cytometry analysis for of NSFs-derived cells after differentiation revealed approximately 13.3% nestin positive, 5.5% Beta-III-tubulin positive, 9% GFAP positive and 7.8% mGalC positive. Functional assays by measurement of calcium influx upon gamma butiric amino acid (GABA) and glutamate stimuli, revealed stimulation in differentiated cells, an indicator of neuronal differentiation. The ability of guinea pig SVZ cells to originate functional neurons in vitro is promising for research and towards a future use of neural stem cells in the therapy of neurological disorders.(AU)
Áreas potencialmente neurogênicas foram identificadas por incorporação de bromodeoxiuridina (BrdU) na zona subventricular (SVZ) dos ventrículos laterais, hipocampo e bulbos olfatórios de cobaias neonatos. Precursores neurais provenientes da SVZ foram cultivados em suspensão, resultando na geração de neuroesferas (NSFs), que quando dissociadas foram capazes de proliferar e gerar novas NSFs. Quando cultivadas na ausência de fatores de crescimento, as células provenientes de NSFs dissociadas apresentaram evidências de diferenciação neuronal, dando origem a células da linhagem neural. Citometria de fluxo em células das NSFs após a diferenciação revelou aproximadamente 13,3% positivas para nestina, 5,5% positivas para Beta-III-tubulina, 9% positivas para GFAP e 7,8% positivas para mGalC. Testes de funcionalidade pela mensuração de influxo de cálcio após estímulo com ácido gama amino butírico (GABA) e glutamato revelaram a estimulação de células diferenciadas, um indicador de função neuronal. A capacidade de células da SVZ de fetos de cobaias originarem células neurais funcionais in vitro é promissora para a pesquisa e eventual uso terapêutico de células tronco em disordens do sistema nervoso.(AU)
Asunto(s)
Animales , Sistema Nervioso Central/fisiología , Cobayas/fisiología , Células-Madre Neurales/fisiología , Animales Recién Nacidos , Técnicas de Cultivo de Célula/veterinaria , Citometría de Flujo/veterinariaRESUMEN
Potentially neurogenic areas were initially identified by incorporation of bromodeoxyuridine (BrdU) in cells underlying the subventricular zone (SVZ) of the lateral ventricles wall, hippocampus and olfactory bulbs of newborn guinea pigs. Neural precursors from the SVZ were cultured in suspension, generating neurospheres (NSFs), which, upon dissociation were able to generate new NSFs. Upon culture in the absence of growth factors, cells dissociated from NSFs displayed evidence for neural differentiation, giving rise to cells from neural lineage. Flow cytometry analysis for of NSFs-derived cells after differentiation revealed approximately 13.3% nestin positive, 5.5% Beta-III-tubulin positive, 9% GFAP positive and 7.8% mGalC positive. Functional assays by measurement of calcium influx upon gamma butiric amino acid (GABA) and glutamate stimuli, revealed stimulation in differentiated cells, an indicator of neuronal differentiation. The ability of guinea pig SVZ cells to originate functional neurons in vitro is promising for research and towards a future use of neural stem cells in the therapy of neurological disorders.(AU)
Áreas potencialmente neurogênicas foram identificadas por incorporação de bromodeoxiuridina (BrdU) na zona subventricular (SVZ) dos ventrículos laterais, hipocampo e bulbos olfatórios de cobaias neonatos. Precursores neurais provenientes da SVZ foram cultivados em suspensão, resultando na geração de neuroesferas (NSFs), que quando dissociadas foram capazes de proliferar e gerar novas NSFs. Quando cultivadas na ausência de fatores de crescimento, as células provenientes de NSFs dissociadas apresentaram evidências de diferenciação neuronal, dando origem a células da linhagem neural. Citometria de fluxo em células das NSFs após a diferenciação revelou aproximadamente 13,3% positivas para nestina, 5,5% positivas para Beta-III-tubulina, 9% positivas para GFAP e 7,8% positivas para mGalC. Testes de funcionalidade pela mensuração de influxo de cálcio após estímulo com ácido gama amino butírico (GABA) e glutamato revelaram a estimulação de células diferenciadas, um indicador de função neuronal. A capacidade de células da SVZ de fetos de cobaias originarem células neurais funcionais in vitro é promissora para a pesquisa e eventual uso terapêutico de células tronco em disordens do sistema nervoso.(AU)