RESUMEN
Regional heterothermy is a strategy used by marine mammals to maintain a high and stable core body temperature, but its identification needs in situ measurements difficult to set up in extant wild organisms and inapplicable to extinct ones. We have analysed the oxygen isotope composition of bioapatite phosphate (δ18Op) from one permanent tooth and from thirty-six skeletal elements of one adult male harbour seal (Phoca vitulina) from the Baie de Somme (Hauts-de-France, France). We propose that the observed intra-skeletal δ18Op variability reflects tissue temperature heterogeneities typical of the pinniped regional heterothermy strategy. Our δ18Op data indicate that bone hydroxylapatite from harbour seal autopod skeletal elements (metacarpals, metatarsals, and phalanxes) mineralises at a lower temperature than that of the bone from the axial skeleton (e.g. vertebrae, ribs, and girdle bones). The results suggest that it is possible to locate a history of regional heterothermies in amphibious marine vertebrates using the δ18Op values of their mineralised tissues. This enables direct evaluation of the thermophysiology of both modern and fossil Pinnipedia from their skeletons opening perspectives on understanding their thermal adaptation to the marine environment in the fossil record. In addition to thermophysiology, oxygen isotope data from the permanent teeth of Pinnipedia, which are formed during the in utero phase from body fluid of the mother and at a stable temperature, could be valuable for locating the geographical areas inhabited by existing Pinnipedia females during their gestation period.
Asunto(s)
Phoca , Animales , Femenino , Masculino , Isótopos de Oxígeno/análisis , Huesos , Fósiles , FranciaRESUMEN
The secondary adaptation of Cetacea to a fully marine lifestyle raises the question of their ability to maintain their water balance in a hyperosmotic environment. Cetacea have access to four potential sources of water: surrounding salt oceanic water, dietary free water, metabolic water and inhaled water vapour to a lesser degree. Here, we measured the 18O/16O oxygen isotope ratio of blood plasma from 13 specimens belonging to two species of Cetacea raised under human care (four killer whales Orcinus orca, nine common bottlenose dolphins Tursiops truncatus) to investigate and quantify the contribution of preformed water (dietary free water, surrounding salt oceanic water) and metabolic water to Cetacea body water using a box-modelling approach. The oxygen isotope composition of Cetacea blood plasma indicates that dietary free water and metabolic water contribute to more than 90% of the total water input in weight for cetaceans, with the remaining 10% consisting of inhaled water vapour and surrounding water accidentally ingested or absorbed through the skin. Moreover, the contribution of metabolic water appears to be more important in organisms with a more lipid-rich diet. Beyond these physiological and conservation biology implications, this study opens up questions that need to be addressed, such as the applicability of the oxygen isotope composition of cetacean body fluids and skeletal elements as an environmental proxy of the oxygen isotope composition of present and past marine waters.
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Delfín Mular , Orca , Animales , Humanos , Isótopos de Oxígeno , Vapor , Cetáceos/fisiologíaRESUMEN
Kainate receptors (KARs) are key regulators of synaptic circuits by acting at pre- and postsynaptic sites through either ionotropic or metabotropic actions. KARs can be activated by kainate, a potent neurotoxin, which induces acute convulsions. Here, we report that the acute convulsive effect of kainate mostly depends on GluK2/GluK5 containing KARs. By contrast, the acute convulsive activity of pilocarpine and pentylenetetrazol is not alleviated in the absence of KARs. Unexpectedly, the genetic inactivation of GluK2 rather confers increased susceptibility to acute pilocarpine-induced seizures. The mechanism involves an enhanced excitability of GluK2-/- CA3 pyramidal cells compared with controls upon pilocarpine application. Finally, we uncover that the absence of GluK2 increases pilocarpine modulation of Kv7/M currents. Taken together, our findings reveal that GluK2-containing KARs can control the excitability of hippocampal circuits through interaction with the neuromodulatory cholinergic system.
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Ácido Kaínico , Pilocarpina , Receptores de Ácido Kaínico , Región CA1 Hipocampal/metabolismo , Colinérgicos/farmacología , Eliminación de Gen , Humanos , Pilocarpina/toxicidad , Células Piramidales/metabolismo , Receptores de Ácido Kaínico/genética , Convulsiones/inducido químicamente , Convulsiones/genética , Receptor de Ácido Kaínico GluK2RESUMEN
Cellular activity in the brain depends on the high energetic support provided by mitochondria, the cell organelles which use energy sources to generate ATP. Acute cannabinoid intoxication induces amnesia in humans and animals, and the activation of type-1 cannabinoid receptors present at brain mitochondria membranes (mtCB1) can directly alter mitochondrial energetic activity. Although the pathological impact of chronic mitochondrial dysfunctions in the brain is well established, the involvement of acute modulation of mitochondrial activity in high brain functions, including learning and memory, is unknown. Here, we show that acute cannabinoid-induced memory impairment in mice requires activation of hippocampal mtCB1 receptors. Genetic exclusion of CB1 receptors from hippocampal mitochondria prevents cannabinoid-induced reduction of mitochondrial mobility, synaptic transmission and memory formation. mtCB1 receptors signal through intra-mitochondrial Gαi protein activation and consequent inhibition of soluble-adenylyl cyclase (sAC). The resulting inhibition of protein kinase A (PKA)-dependent phosphorylation of specific subunits of the mitochondrial electron transport system eventually leads to decreased cellular respiration. Hippocampal inhibition of sAC activity or manipulation of intra-mitochondrial PKA signalling or phosphorylation of the Complex I subunit NDUFS2 inhibit bioenergetic and amnesic effects of cannabinoids. Thus, the G protein-coupled mtCB1 receptors regulate memory processes via modulation of mitochondrial energy metabolism. By directly linking mitochondrial activity to memory formation, these data reveal that bioenergetic processes are primary acute regulators of cognitive functions.
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Cannabinoides/efectos adversos , Trastornos de la Memoria/inducido químicamente , Memoria/efectos de los fármacos , Memoria/fisiología , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Adenilil Ciclasas/metabolismo , Animales , Cannabinoides/metabolismo , Respiración de la Célula/efectos de los fármacos , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Transporte de Electrón/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Femenino , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/patología , Masculino , Trastornos de la Memoria/enzimología , Trastornos de la Memoria/metabolismo , Trastornos de la Memoria/patología , Ratones , Membranas Mitocondriales/efectos de los fármacos , Membranas Mitocondriales/enzimología , Membranas Mitocondriales/metabolismo , NADH Deshidrogenasa/metabolismo , Fosforilación Oxidativa/efectos de los fármacos , Receptor Cannabinoide CB1/deficiencia , Receptor Cannabinoide CB1/genética , Receptor Cannabinoide CB1/metabolismo , Transducción de Señal/efectos de los fármacos , Transmisión Sináptica/efectos de los fármacosRESUMEN
This paper offers a re-description of one of the oldest (Lower Hettangian, Lower Jurassic) plesiosaurians (Reptilia: Sauropterygia) from Germany and discusses its phylogenetic relevance. Lindwurmia thiuda, new genus and species, is a moderately sized plesiosaur (estimated size between 2 and 3 m long) exhibiting several plesiomorphic features. Although it presents a short and robust premaxillary rostrum, constricted at the premaxilla-maxilla suture as observed in Rhomaleosauridae, its skull and skeleton share a great number of characters with basal sauropterygians and basal plesiosaurians: premaxillae and maxillae in contact posterior to the external nares, absence of contact between the vomers and the maxillae posterior to the internal nares, cervical zygapophyses wider than the vertebral centrum width and curved anterior border of the humerus. Phylogenetic analyses variably place Lindwurmia as sister taxon to Anningasaura and in a basal position to all other plesiosaurians or recover it among rhomaleosaurids. Most of the oldest plesiosaurians are known from the Hettangian or Hettangian-possibly Sinemurian strata of the UK (Lyme Regis and Street); Lindwurmia thus represents one of the oldest European taxa found outside of the UK.
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Fósiles/anatomía & histología , Filogenia , Reptiles/anatomía & histología , Reptiles/clasificación , Animales , Alemania , Cráneo/anatomía & histología , Especificidad de la EspecieRESUMEN
Brain endocasts obtained from computed tomography (CT) are now widely used in the field of comparative neuroanatomy. They provide an overview of the morphology of the brain and associated tissues located in the cranial cavity. Through anatomical comparisons between species, insights on the senses, the behavior, and the lifestyle can be gained. Although there are many studies dealing with mammal and bird endocasts, those performed on the brain endocasts of squamates are comparatively rare, thus limiting our understanding of their morphological variability and interpretations. Here, we provide the first comparative study of snake brain endocasts in order to bring new information about the morphology of these structures. Additionally, we test if the snake brain endocast encompasses a phylogenetic and/or an ecological signal. For this purpose, the digital endocasts of 45 snake specimens, including a wide diversity in terms of phylogeny and ecology, were digitized using CT, and compared both qualitatively and quantitatively. Snake endocasts exhibit a great variability. The different methods performed from descriptive characters, linear measurements and the outline curves provided complementary information. All these methods have shown that the shape of the snake brain endocast contains, as in mammals and birds, a phylogenetic signal but also an ecological one. Although phylogenetically related taxa share several similarities between each other, the brain endocast morphology reflects some notable ecological trends: e.g. (i) fossorial species possess both reduced optic tectum and pituitary gland; (ii) both fossorial and marine species have cerebral hemispheres poorly developed laterally; (iii) cerebral hemispheres and optic tectum are more developed in arboreal and terrestrial species.
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Encéfalo/anatomía & histología , Serpientes/anatomía & histología , Anatomía Comparada , Animales , Filogenia , Tomografía Computarizada por Rayos XRESUMEN
The Posidonienschiefer Formation (Toarcian) of Holzmaden, Baden-Württemberg in southwestern Germany has yielded several excellently preserved plesiosaurian specimens and received considerable research attention. The plesiosaurians found within these deposits are always significantly outnumbered by ichthyosaurs, and close examination of these rare specimens is crucial to a better understanding of the diversity and palaeoecology of Plesiosauria in this very peculiar ecosystem. The plesiosaurian specimen SMNS 51945 found in this area is a juvenile individual consisting of a partial, crushed skull and an exquisitely preserved post-cranial skeleton. Its anatomical characters seem to differ from the long-necked plesiosauroids Microcleidus brachypterygius and Seeleyosaurus guilelmiimperatoris that are the most abundant taxa within the plesiosaurian assemblage. The post-cranial skeleton preserves very likely soft tissues composed of buff-coloured and dark-coloured structures around the vertebral column and hindlimb of the animal. A network of buff-coloured fibres located posterior to the hindlimb most likely represents phosphatised collagen fibres as already found in some ichthyosaur specimens, confirming that wing area in plesiosaurians was much larger than that suggested by skeletal remains alone. The specimen also contains gastroliths (sand-sized grains mainly composed of quartz) in the stomach cavity suggesting the animal spent at least some of its time in shallow coastal waters, tens or hundreds of kilometres from the final place of burial.
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Huesos/anatomía & histología , Fósiles , Filogenia , Reptiles/anatomía & histología , Reptiles/clasificación , Animales , AlemaniaRESUMEN
Mesozoic marine reptiles went through a severe turnover near the end of the Triassic. Notably, an important extinction event affected ichthyosaurs, sweeping a large part of the group. This crisis is, however, obscured by an extremely poor fossil record and is regarded as protracted over the entire Norian-earliest Jurassic interval, for the lack of a more precise scenario. The iconic whale-sized shastasaurid ichthyosaurs are regarded as early victims of this turnover, disappearing by the middle Norian. Here we evaluate the pattern of this turnover among ichthyosaurs by analysing the faunal record of two Rhaetian localities. One locality is Autun, eastern France; we rediscovered in this material the holotypes or partial 'type' series of Rachitrema pellati, Actiosaurus gaudryi, Ichthyosaurus rheticus, Ichthyosaurus carinatus and Plesiosaurus bibractensis; a revised taxonomic scheme is proposed. The second assemblage comes from a new locality: Cuers, southeastern France. Both these assemblages provide several lines of evidence for the presence of shastasaurid-like ichthyosaurs in the Rhaetian of Europe. These occurrences suggest that both the demise of shastasaurids and the sudden radiation of neoichthyosaurians occurred within a short time window; this turnover appears not only more abrupt but also more complex than previously postulated and adds a new facet of the end-Triassic mass extinction.
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Extinción Biológica , Fósiles , Reptiles/anatomía & histología , Animales , Huesos/anatomía & histología , Francia , Especificidad de la EspecieRESUMEN
OBJECTIVES: Determine the feasibility of allied health assistant (AHA) management of people with hip fracture an acute hospital. DESIGN: Assessor-blind, parallel, feasibility randomised controlled trial with qualitative component. SETTING: Acute orthopaedic ward. PARTICIPANTS: People with surgically-managed hip fracture, who walked independently pre-fracture and had no cognitive impairment. INTERVENTIONS: Rehabilitation from an AHA, under the supervision of a physiotherapist, compared with rehabilitation from a physiotherapist. MAIN OUTCOME MEASURES: Feasibility was evaluated according to focus areas of demand, acceptability, practicality and implementation. Secondary outcomes included estimates of effect of adherence to hip fracture mobilisation guidelines, discharge destination, 30-day readmission, functional activity, and length of stay. RESULTS: Fifty people were allocated to receive rehabilitation from an AHA (nâ¯=â¯25) or physiotherapist (nâ¯=â¯25). AHA rehabilitation had high demand with 60% of eligible participants recruited. Satisfaction with AHA rehabilitation was comparable with physiotherapy rehabilitation (acceptability). The AHA group received an average of 11â¯min (95% CI 4 to 19) more therapy per day than the physiotherapy group (implementation). The AHA group may have had lower cost of acute care (MD -$3 808 95% CI -7 651 to 35) and adverse events were comparable between groups (practicality). The AHA group may have been 22% (HR 1.22, 95% CI 0.92 to 1.61) more likely to walk on any day and may have had a shorter length of stay (MD -0.8 days, 95% CI -2.3 to 0.7). CONCLUSIONS: AHA management of patients with hip fracture was feasible and may improve adherence to mobilisation guidelines and reduce cost of care and length of stay. CLINICAL TRIAL REGISTRATION NUMBER: ACTRN12620000877987. CONTRIBUTION OF THE PAPER.
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Técnicos Medios en Salud , Estudios de Factibilidad , Fracturas de Cadera , Cooperación del Paciente , Humanos , Fracturas de Cadera/rehabilitación , Femenino , Masculino , Anciano , Anciano de 80 o más Años , Modalidades de Fisioterapia , Método Simple Ciego , Tiempo de Internación , Ambulación PrecozRESUMEN
INTRODUCTION: Key to improving outcomes for patients with multimorbidity is increasing mobility through prescription of a physical activity programme, but this can be difficult to achieve in acute hospital settings. One approach that would assist physiotherapists to increase levels of physical activity is delegation of rehabilitation to allied health assistants. We aim to conduct a randomised controlled trial to determine the feasibility of an allied health assistant providing daily inpatient mobility rehabilitation for patients with multimorbidity. METHODS AND ANALYSIS: Using a parallel group randomised controlled design, participants will be allocated to allied health assistant mobility rehabilitation or physiotherapist mobility rehabilitation. Adult inpatients (n=60) in an acute hospital with a diagnosis of multimorbidity who walked independently preadmission will be included. The experimental group will receive routine mobility rehabilitation, including daily mobilisation, from an allied health assistant under the supervision of a physiotherapist. The comparison group will receive routine rehabilitation from a physiotherapist. Feasibility will be determined using the following areas of focus in Bowen's feasibility framework: Acceptability (patient satisfaction); demand (proportion of patients who participate); implementation (time allied health assistant/physiotherapist spends with participant, occasions of service); and practicality (cost, adverse events). Staff involved in the implementation of allied health assistant rehabilitation will be interviewed to explore their perspectives on feasibility. Secondary outcomes include: Physical activity (daily time spent walking); daily mobilisation (Y/N); discharge destination; hospital readmission; falls; functional activity (Modified Iowa Level of Assistance Scale); and length of stay. Descriptive statistics will be used to describe feasibility. Secondary outcomes will be compared between groups using Poisson or negative binomial regression, Cox proportional hazards regression, survival analysis, linear regression or logistic regression. ETHICS AND DISSEMINATION: Ethics approval was obtained from Peninsula Health (HREC/97 431/PH-2023). Findings will be disseminated in peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: Australian and New Zealand Clinical Trial Registry ACTRN12623000584639p.
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Multimorbilidad , Modalidades de Fisioterapia , Adulto , Humanos , Estudios de Factibilidad , Australia , Hospitales , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
INTRODUCTION: Guidelines for hip fracture care state that patients with hip fracture should be mobilised on the day after surgery and at least once a day thereafter. However, compliance with these guidelines is poor. One approach that would assist physiotherapists to meet mobility guidelines after hip fracture is to delegate the provision of daily mobilisation to allied health assistants under their supervision. Therefore, we plan to conduct a randomised controlled trial to determine the feasibility of an allied health assistant providing daily inpatient rehabilitation to patients with hip fracture. METHODS AND ANALYSIS: Using a parallel group randomised controlled design with one-to-one allocation, participants will be randomly allocated to an experimental group (allied health assistant management) or a comparison group (physiotherapist management). Inclusion criteria are: adult with diagnosis of hip fracture; inpatient in acute hospital; walked independently pre-hip fracture and able to communicate in conversational English. The experimental group will receive routine physiotherapy rehabilitation, including daily mobilisation, from an allied health assistant following initial physiotherapist assessment. The comparison group will receive routine rehabilitation from a physiotherapist. The primary outcome will be the feasibility of allied health assistant management of patients with hip fracture. Feasibility will be determined using the following areas of focus in Bowen's feasibility framework: acceptability (patient satisfaction), demand (proportion of patients who participate), implementation (time allied health assistant/physiotherapist spends with participant, occasions of service) and practicality (cost, adverse events). Staff involved in the implementation of allied health assistant care will be interviewed to explore their perspectives on feasibility. Secondary outcomes include compliance with daily mobilisation guidelines, discharge destination, hospital readmission, falls, functional activity and length of stay. We aim to recruit 50 participants. Descriptive statistics will be used to describe feasibility and mobilisation rates will be calculated using Cox proportional hazards regression to compare compliance with mobilisation guidelines. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Peninsula Health human research ethics committee (HREC/63 005/PH-2020). The findings will be disseminated in peer-reviewed journals and conference presentations. TRAIL REGISTRATION NUMBER: Australian and New Zealand Clinical Trial Registry; ACTRN12620000877987; Pre-results.
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Fracturas de Cadera , Accidentes por Caídas , Adulto , Australia , Estudios de Factibilidad , Humanos , Modalidades de Fisioterapia , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Recent advances in neuroscience have positioned brain circuits as key units in controlling behavior, implying that their positive or negative modulation necessarily leads to specific behavioral outcomes. However, emerging evidence suggests that the activation or inhibition of specific brain circuits can actually produce multimodal behavioral outcomes. This study shows that activation of a receptor at different subcellular locations in the same neuronal circuit can determine distinct behaviors. Pharmacological activation of type 1 cannabinoid (CB1) receptors in the striatonigral circuit elicits both antinociception and catalepsy in mice. The decrease in nociception depends on the activation of plasma membrane-residing CB1 receptors (pmCB1), leading to the inhibition of cytosolic PKA activity and substance P release. By contrast, mitochondrial-associated CB1 receptors (mtCB1) located at the same terminals mediate cannabinoid-induced catalepsy through the decrease in intra-mitochondrial PKA-dependent cellular respiration and synaptic transmission. Thus, subcellular-specific CB1 receptor signaling within striatonigral circuits determines multimodal control of behavior.
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Encéfalo/metabolismo , Receptor Cannabinoide CB1/metabolismo , Transducción de Señal/fisiología , Transmisión Sináptica/fisiología , Animales , Encéfalo/efectos de los fármacos , Agonistas de Receptores de Cannabinoides/farmacología , Antagonistas de Receptores de Cannabinoides/farmacología , Catalepsia/inducido químicamente , Membrana Celular/metabolismo , Células HEK293 , Células HeLa , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Nocicepción/efectos de los fármacos , Nocicepción/fisiología , Transducción de Señal/efectos de los fármacos , Transmisión Sináptica/efectos de los fármacosRESUMEN
The collapse of marine ecosystems during the end-Cretaceous mass extinction involved the base of the food chain [1] up to ubiquitous vertebrate apex predators [2-5]. Large marine reptiles became suddenly extinct at the Cretaceous-Paleogene (K/Pg) boundary, whereas other contemporaneous groups such as bothremydid turtles or dyrosaurid crocodylomorphs, although affected at the familial, genus, or species level, survived into post-crisis environments of the Paleocene [5-9] and could have found refuge in freshwater habitats [10-12]. A recent hypothesis proposes that the extinction of plesiosaurians and mosasaurids could have been caused by an important drop in sea level [13]. Mosasaurids are unusually diverse and locally abundant in the Maastrichtian phosphatic deposits of Morocco, and with large sharks and one species of elasmosaurid plesiosaurian recognized so far, contribute to an overabundance of apex predators [3, 7, 14, 15]. For this reason, high local diversity of marine reptiles exhibiting different body masses and a wealth of tooth morphologies hints at complex trophic interactions within this latest Cretaceous marine ecosystem. Using calcium isotopes, we investigated the trophic structure of this extinct assemblage. Our results are consistent with a calcium isotope pattern observed in modern marine ecosystems and show that plesiosaurians and mosasaurids indiscriminately fall in the tertiary piscivore group. This suggests that marine reptile apex predators relied onto a single dietary calcium source, compatible with the vulnerable wasp-waist food webs of the modern world [16]. This inferred peculiar ecosystem structure may help explain plesiosaurian and mosasaurid extinction following the end-Cretaceous biological crisis.
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Extinción Biológica , Cadena Alimentaria , Océanos y Mares , Reptiles/fisiología , Tiburones/fisiología , Animales , Evolución Biológica , Isótopos de Calcio/análisis , FósilesRESUMEN
Fluoroacetate has been widely used to inhibit glia metabolism in vivo. It has yet to be shown what the effects of chronic intrathecal infusion of fluoroacetate on nociceptive behavioral testing are. The effects of chronic infusion of fluoroacetate (5 nmoles/h) for 2 weeks were examined in normal rats. Chronic intrathecal fluoroacetate did not alter mechanical threshold (von Frey filaments), responses to supra-threshold mechanical stimuli (von Frey filaments), responses to hot (hot plate) or cool (acetone test) stimuli and did not affect motor performance of the animals, which was tested with rotarod. This suggests that fluoroacetate at appropriate dose did not suppress neuronal activity in the spinal cord.
RESUMEN
There are many parallels between the hematopoietic and the nervous systems in terms of mechanisms regulating their development and functions. In neuroinflammatory diseases, interaction between the immune and nervous systems through shared molecules is suspected to trigger an inappropriate crosstalk and lead to demyelination and axonal loss. Here we focus on semaphorins and their functions in the nervous and immune systems and point out the deleterious effect of an immune semaphorin, semaphorin 4D (Sema4D)/CD100, on oligodendrocyte integrity and survival. We propose immune semaphorins as new candidates involved in the pathogenic mechanisms of neuroinflammatory diseases, promoting demyelination, and impairing neuroregeneration.
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Sistema Nervioso Central/inmunología , Degeneración Nerviosa/inmunología , Regeneración Nerviosa/inmunología , Semaforinas/inmunología , Linfocitos T/inmunología , Animales , Antígenos CD/inmunología , Supervivencia Celular , Humanos , Inmunidad Celular , Inflamación/inmunología , Neuroinmunomodulación , Oligodendroglía/citología , Oligodendroglía/inmunologíaRESUMEN
Activation of N-methyl-d-aspartate (NMDA) receptors is critical for hypersensitivity in chronic neuropathic pain. Since astroglia can regulate NMDA receptor activation by releasing the NMDA receptor co-agonist d-serine, we investigated the role of NMDA receptor and d-serine in neuropathic chronic pain. Male Wistar rats underwent right L5-L6 spinal nerve ligation or sham surgery and were tested for mechanical allodynia and hyperalgesia after 14 days. Acute intrathecal administration of the NMDA receptor antagonist d-AP5 as well as chronic administration of the glia metabolism inhibitor fluoroacetate significantly reduced mechanical allodynia in neuropathic rats. The effect of fluoroacetate was reversed by acutely administered intrathecal d-serine. Degrading d-serine using acute intrathecal administration of d-aminoacid oxidase also reduced pain symptoms. Immunocytochemistry showed that about 70% of serine racemase, the synthesizing enzyme of d-serine, was expressed in astrocyte processes in the superficial laminae of L5 dorsal horn. Serine racemase expression was upregulated in astrocyte processes in neuropathic rats compared to sham rats. These results show that neuropathic pain depends upon glial d-serine that co-activates spinal NMDA receptors.
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Neuralgia/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Serina/metabolismo , Médula Espinal/metabolismo , Animales , Proteína Ácida Fibrilar de la Glía/metabolismo , Hiperalgesia/fisiopatología , Masculino , Neuralgia/fisiopatología , Estimulación Física , Racemasas y Epimerasas/metabolismo , Ratas Wistar , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , TactoRESUMEN
Expression of aversive memories is key for survival, but the underlying brain mechanisms are not fully understood. Medial habenular (MHb) axons corelease glutamate and acetylcholine onto target postsynaptic interpeduncular (IPN) neurons, but their role in aversive memories has not been addressed so far. We found that cannabinoid type 1 receptors (CB1R), key regulators of aversive responses, are present at presynaptic terminals of MHb neurons in the IPN. Conditional deletion of CB1R from MHb neurons reduces fear-conditioned freezing and abolishes conditioned odor aversion in mice, without affecting neutral or appetitively motivated memories. Interestingly, local inhibition of nicotinic, but not glutamatergic receptors in the target region IPN before retrieval, rescues these phenotypes. Finally, optogenetic electrophysiological recordings of MHb-to-IPN circuitry revealed that blockade of CB1R specifically enhances cholinergic, but not glutamatergic, neurotransmission. Thus, presynaptic CB1R control expression of aversive memories by selectively modulating cholinergic transmission at MHb synapses in the IPN.
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Reacción de Prevención/fisiología , Miedo/fisiología , Habénula/fisiología , Receptor Cannabinoide CB1/fisiología , Animales , Miedo/psicología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Receptor Cannabinoide CB1/deficienciaRESUMEN
Hunger arouses sensory perception, eventually leading to an increase in food intake, but the underlying mechanisms remain poorly understood. We found that cannabinoid type-1 (CB1) receptors promote food intake in fasted mice by increasing odor detection. CB1 receptors were abundantly expressed on axon terminals of centrifugal cortical glutamatergic neurons that project to inhibitory granule cells of the main olfactory bulb (MOB). Local pharmacological and genetic manipulations revealed that endocannabinoids and exogenous cannabinoids increased odor detection and food intake in fasted mice by decreasing excitatory drive from olfactory cortex areas to the MOB. Consistently, cannabinoid agonists dampened in vivo optogenetically stimulated excitatory transmission in the same circuit. Our data indicate that cortical feedback projections to the MOB crucially regulate food intake via CB1 receptor signaling, linking the feeling of hunger to stronger odor processing. Thus, CB1 receptor-dependent control of cortical feedback projections in olfactory circuits couples internal states to perception and behavior.
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Agonistas de Receptores de Cannabinoides/farmacología , Ingestión de Alimentos/fisiología , Endocannabinoides/fisiología , Conducta Alimentaria/fisiología , Vías Olfatorias/fisiología , Percepción Olfatoria/fisiología , Receptor Cannabinoide CB1/metabolismo , Transmisión Sináptica/fisiología , Animales , Ingestión de Alimentos/efectos de los fármacos , Endocannabinoides/metabolismo , Retroalimentación Fisiológica/fisiología , Conducta Alimentaria/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Bulbo Olfatorio/efectos de los fármacos , Bulbo Olfatorio/metabolismo , Bulbo Olfatorio/fisiología , Vías Olfatorias/efectos de los fármacos , Vías Olfatorias/metabolismo , Percepción Olfatoria/efectos de los fármacos , Receptor Cannabinoide CB1/genética , Transmisión Sináptica/efectos de los fármacosAsunto(s)
Analgésicos Opioides/uso terapéutico , Artralgia/tratamiento farmacológico , Artralgia/enfermería , Morfina/uso terapéutico , Luxación del Hombro/enfermería , Adolescente , Adulto , Artralgia/etiología , Humanos , Masculino , Rol de la Enfermera , Autonomía Profesional , Luxación del Hombro/complicaciones , Adulto JovenRESUMEN
What the body temperature and thermoregulation processes of extinct vertebrates were are central questions for understanding their ecology and evolution. The thermophysiologic status of the great marine reptiles is still unknown, even though some studies have suggested that thermoregulation may have contributed to their exceptional evolutionary success as apex predators of Mesozoic aquatic ecosystems. We tested the thermal status of ichthyosaurs, plesiosaurs, and mosasaurs by comparing the oxygen isotope compositions of their tooth phosphate to those of coexisting fish. Data distribution reveals that these large marine reptiles were able to maintain a constant and high body temperature in oceanic environments ranging from tropical to cold temperate. Their estimated body temperatures, in the range from 35 degrees +/- 2 degrees C to 39 degrees +/- 2 degrees C, suggest high metabolic rates required for predation and fast swimming over large distances offshore.