1,721,127 research outputs found
On the synaptic rearrangement in the hypothalamus and the periaqueductal gray in an animal model of obesity
No full textL'obesità è un problema mondiale, che colpisce la salute delle persone e gravare sistemi sanitari. Dal punto di vista del biologo è una complessa interazione di endocrine e neurali meccanismi sottostanti assunzione di cibo, in particolare, una delle sue forme patologiche porta all'obesità. È interessante notare che i pazienti così come modelli animali affetti da anomalie di visualizzazione comportamento alimentare nocicezione alterato.
Un modello di topo fama per l'obesità è la leptina-carente ob/ob topo, il nostro laboratorio ha dimostrato che l'innervazione prevalentemente eccitatoria dei neuroni esprimono orexin (OX-N) nell'ipotalamo laterale (LH) di topi WT è riorganizzato in favore di gli ingressi inibitori di LH di topi ob/ob. Inoltre, il rilascio delle vescicole dagli ingressi inibitori è soppressa via recettore dei cannabinoidi di tipo 1 (CB1) attivazione. Su depolarizzazione un neurone oressinergico sintetizza e "rilascia" endocannabinoidi (eCBs), molto probabilmente 2-AG, che viaggia retrograda al terminale presinaptico e attiva i recettori CB1 presinaptici, sopprimendo così il rilascio delle vescicole da questi terminali (un meccanismo chiamato: depolarizzazione-indotta soppressione di inibizione o DSI). Qui, ho dimostrato che l'innervazione eccitatoria funzionale di OX-N non differiva tra ob/ob e topi WT. Inoltre, l'attivazione dei recettori CB1 presinaptici soppresso il rilascio delle vescicole da ingressi eccitatori, sia wt e topi ob/ob, nella stessa misura. Lo squilibrio di eccitatori funzionale e ingressi inibitori in ob/ob recettori CB1 presinaptici topi, putativamente, lascia OX-N con una membrana iperpolarizzato potenziale e un'attività di cottura ridotta, su depolarizzazione, tuttavia, eCBs sarebbe sintetizzato e rilasciato, viaggi in e attivare , che si trova principalmente su fattori inibitori, sopprimendo il rilascio delle vescicole e disinibendo quindi OX-N. Neuroni oressinergico possiedono vaste proiezioni in tutto il cervello, i.a. per il sistema della dopamina mesoaccumbal e (HPA) ipotalamo-ipofisi-surrene. L'attivazione di queste due circuiti, putativamente, provoca l'aumentata assunzione di cibo visto in ob/ob mouse.
Un'altra area di destinazione di OX-N è il grigio periacqueduttale (PAG), che è noto a svolgere un ruolo chiave nella nocicezione attraverso le vie discendenti antinocicettivi. E 'stato riportato che i pazienti così come modelli animali affetti da comportamento alimentare anormale mostrano anche nocicezione alterata. Inoltre, la somministrazione di orexina A (OX-A) è stata dimostrata per sopprimere le correnti postsinaptiche inibitorie in recettori CB1 modo attivazione mediata, eventualmente, causando una depolarizzazione del potenziale di membrana dei neuroni PAG e, infine, un aumento di cottura attività. Curiosamente, queste osservazioni in vitro si traducono in un comportamento, OX-Un'amministrazione nel PAG elevato la soglia del dolore nei ratti durante il test della coda-flick. ob/ob topo mostravano un elevato livello di OX-A in PAG, simile alla situazione dopo OX-A amministrazione, quindi, abbiamo ipotizzato che i neuroni PAG proiettando al midollo rostroventral (prossimo passo gerarchica dopo PAG nelle vie discendenti antinocicettivi) erano più depolarizzato e hanno un'attività di cottura superiore in topi ob/ob rispetto al peso. Infatti, bloccando il recettore orexina 1 iperpolarizzato il potenziale di membrana e riduce l'attività dei neuroni ob/ob PAG, ma non i neuroni wt PAG. Inoltre, PAG neuroni di topi ob/ob visualizzati potenziale potenziale soglia azione iperpolarizzato rispetto ai topi WT, il che significa che i neuroni ob/ob PAG sono più propensi ad avviare un potenziale d'azione di neuroni WT PAG. Così, suggerendo che l'attivazione dei neuroni PAG dal attivati ingressi oressinergico risultati in una soglia del dolore elevata ulteriormente attivando le vie discendenti antinocicettivi.
In conclusione, l'interruttore di innervazione su OX-N a favore di ingressi inibitori, causato dall'assenza di leptina nel ob/ob topo, attiva OX-N inibendo loro ingressi principalmente inibitori dall'attivazione del recettore CB1 BCE-mediata, conseguente la soppressione del rilascio di vescicole (DSI). Questi disinibito OX-N attivare aree di destinazione in tutto il cervello, come il sistema della dopamina mesoaccumbal e asse HPA, modulando in tal modo il comportamento alimentare. Inoltre, le proiezioni oressinergico a PAG depolarizza il potenziale di membrana e aumenta l'attività dei neuroni PAG proiettano al midollo rostroventral, aumentando così la soglia del dolore.Obesity is a worldwide problem, affecting peoples‘ health and burdening healthcare systems. It is a complex interaction of endocrine and neural mechanisms underlying food intake, in particular, one of its pathological forms leading to obesity. Interestingly, patients as well as animal models suffering from abnormal feeding behavior display altered nociception.
A renown mouse model for obesity is the leptin-deficient ob/ob mouse, our laboratory has demonstrated that the mainly excitatory innervation of orexin-expressing neurons (OX-N) in the lateral hypothalamus (LH) of wt mice is rearranged in favor of the inhibitory inputs in LH of ob/ob mice. Furthermore, the vesicle release from the inhibitory inputs is suppressed by endocannabinoids (eCBs) activating cannabinoid receptor type 1 (CB1) activation. The eCBs, most likely 2-AG, originate from the postsynaptic terminals, where they are being synthesized and “released“ as a reaction to depolarization (a mechanism called: depolarization-induced suppression of inhibition or DSI). Here, I demonstrated that the functional excitatory innervation of OX-N did not differ between ob/ob and wt mice. Furthermore, the activation of presynaptic CB1 receptors suppressed the vesicle release from excitatory inputs, in both wt and ob/ob mice, to the same extent. The imbalance of functional excitatory and inhibitory inputs in ob/ob mice, putatively, leaves OX-N with a hyperpolarized membrane potential and a reduced firing activity. Activation of CB1 receptors, mainly located on inhibitory inputs, eventually activate OX-N by disinhibiting them. Orexinergic neurons possess vast projections throughout the brain, i.a. to the mesoaccumbal dopamine system and the hypothalamus-pituitary-adrenal (HPA) axis. The activation of these two circuits, putatively, results in the increased food intake seen in the ob/ob mouse.
Another target area of OX-N is the periaqueductal gray (PAG), playing a key role in nociception via the descending antinociceptive pathways. It has been reported that patients as well as animal models suffering from abnormal feeding behavior also display altered nociception. Furthermore, the administration of orexin A (OX-A) has been demonstrated to suppress inhibitory postsynaptic currents in CB1 receptor activation-mediated way, eventually, resulting in a depolarization of the membrane potential of PAG neurons and, finally, in an increase of firing activity. Intriguingly, these in vitro observations translate to behavior, OX-A administration into PAG elevated the pain threshold in rats during the tail-flick test. ob/ob mice displayed an elevated level of OX-A in PAG, similar to the situation after OX-A administration, hence, we hypothesized that the PAG neurons projecting to the rostroventral medulla were more depolarized and have a higher firing activity in ob/ob mice compared to wt. Indeed, blocking the orexin 1 receptor hyperpolarized the membrane potential and reduced the firing activity of ob/ob PAG neurons, but not wt PAG neurons. Furthermore, ob/ob PAG neurons were more likely to initiate an action potential than wt PAG neurons. Thus, suggesting that the activation of PAG neurons by activated orexinergic inputs results in an elevated pain threshold by further activating the descending antinociceptive pathways.
In conclusion, the switch of innervation onto OX-N in favor of inhibitory inputs, caused by the absence of leptin in the ob/ob mouse, activates OX-N by inhibiting their mainly inhibitory inputs by eCB-mediated CB1 receptor activation, resulting in the suppression of vesicle release (DSI). These disinhibited OX-N activate target areas throughout the brain, such as the mesoaccumbal dopamine system and HPA axis, thereby modulating feeding behavior. Furthermore, orexinergic projections to PAG depolarizes the membrane potential and increases the firing activity of PAG neurons projecting to the rostroventral medulla, thereby raising the pain threshold
Endocannabinoids and energy homeostasis: an update.
No full textThe endocannabinoid system (ECS) is a widespread intercellular signaling system that plays a critical role in energy homeostasis, meant as the precise matching of caloric intake with energy expenditure which normally keeps body weight stable over time. Complex interactions between environmental and neurohormonal systems directly contribute to the balance of energy homeostasis. This review highlights established and more recent data on the brain circuits in which the ECS plays an important regulatory role, with focus on the hypothalamus, a region where numerous interacting systems regulating feeding, satiety, stress, and other motivational states coexist. Although not meant as an exhaustive review of the field, this article will discuss how endocannabinoid tone, in addition to reinforcing reward circuitries and modulating food intake and the salience of food, controls lipid and glucose metabolism in several peripheral organs, particularly the liver and adipose tissue. Direct actions in the skeletal muscle and pancreas are also emerging and are briefly discussed. This review provides new perspectives into endocannabinoid control of the neurochemical causes and consequences of energy homeostasis imbalance, a knowledge that might lead to new potential treatments for obesity and related morbidities
Effects of acute systemic administration of serotonin2A/C receptor ligands in a delay-based decision-making task in rats.
No full textSerotonin (5-hydoxytryptamine; 5-HT) has been implicated in the regulation of impulsivity, and high levels of impulsive behavior are associated with certain neuropsychiatric disorders. An important aspect of impulsive behavior is the inability to tolerate delays in reward. This study investigated the effects of the 5-HT2A/C receptor agonist DOI [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropan hydrochloride] and the 5-HT2A receptor antagonist ketanserin on impulsive behavior measured in a delay-based decision-making task. Male Wistar rats were trained in a T-maze to choose a large but 10-s delayed food reward instead of a small immediate reward. After stable baseline performance (70% choice of large reward), the effects of acute systemic administration of 5-HT2A/C receptor ligands on waiting capacity were tested. Systemic administration of DOI (0.1, 0.3, and 0.5 mg/kg) impaired waiting capacity in a dose-dependent manner, whereas ketanserin had no effect. When combined with ketanserin, DOI did not impair waiting capacity. The data indicate that DOI-induced impairment of the ability to discount a delay in reward in a T-maze is probably regulated by 5-HT2A receptors. Furthermore, this study extends the existing findings of 5-HT2 receptor involvement in different tasks of delay aversion in rodents
The uplift of the East Africa - Arabia swell
No full textThe East Africa - Arabia topographic swell is an anomalously high-elevation region of ~4000 km long (from southern Ethiopia to Jordan) and ~ 1500 km wide (from Egypt to Saudi Arabia) extent. The swell is dissected by the Main Ethiopian, Red Sea, and Gulf of Aden rifts, and characterized by widespread basaltic volcanic deposits emplaced from the Eocene to the present. Geochemical and geophysical data confirm the involvement of mantle processes in swell formation; however, they have not been able to fully resolve some issues, e.g., regarding the number and location of plumes and uplift patterns. This study addresses these questions and provides a general evolutionary model of the region by focusing on the present topographic configuration through a quantitative analysis and correlating long and intermediate wavelength features with mantle and rifting processes. Moreover, the isostatic and dynamic components of topography have been evaluated considering a range of seismic tomographic models for the latter. When interpreted jointly with geological data including volcanic deposits, the constraints do imply causation by a single process which shaped the past and present topography of the study area: the upwelling of the Afar superplume. Once hot mantle material reached the base of the lithosphere below the Horn of Africa during the Late Eocene, the plume flowed laterally toward the Levant area guided by preexisting discontinuities in the Early Miocene. Plume material reached the Anatolian Plateau in the Late Miocene after slab break-off and the consequent formation of a slab window. During plume material advance, buoyancy forces led to the formation of the topographic swell and tilting of the Arabia Peninsula. The persistence of mantle support beneath the study area for tens of million years also affected the formation and evolution of the Nile and Euphrates-Tigris fluvial networks. Subsequently, surface processes, tectonics, and volcanism partly modified the initial topography and shaped the present-day landscape
The fairy circles of Kaokoland (North-West Namibia) – origin, distribution, and characteristics
No full textEmbedded in species-poor grasslands, fairy circles are circular or sub-circular patches devoid of any vegetation. Characteristically, the circumference of each circle shows a band of more densely packed taller tussocks within a shorter, more sparse grassland matrix. The average diameter of the circles is between 5–8 m. Restricted to sites showing deep sandy deposits, in Namibia, fairy circles occur in a broken belt in the pro-Namib from southern Angola to the Orange River (Republic of South Africa). The distribution of fairy circles is significantly limited to areas with an average of 50–100 mm of annual precipitation. Based on remote sensing methods and expeditions, a map of the distribution area of fairy circles in Kaokoland (NW Namibia) was drawn up. The map indicates that fairy circles are more widely spread over the western parts of Kaokoland than previously re-ported. The two different active biological hypotheses of the fairy circles ’ origin comprise 1. the al-lelopathic interaction between Euphorbia damarana and the contemporary herbaceous vegetation (Theron 1979) and 2. the involvement of harvester termites (Moll 1994). Both hypotheses are dis-cussed and a model about the origin and dynamic of fairy circles is presented. This model includes the foraging behaviour of the harvester termite Hodotermes mossambicus which is the prime causal factor in forming the fairy circles of Kaokoland. Eingebettet in artenarme Grasländer, bilden Feenkreise runde bzw. kreisförmige vegetationslose Flächen. Als typisches Merkmal besitzen diese Flächen einen Rand, der aus dicht stehenden großen Grashorsten gebildet wird und sich deutlich von der spärlichen Grasland-Matrix abhebt. De
Mantle convection in the Middle East: Reconciling Afar upwelling, Arabia indentation and Aegean trench rollback
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Isostasy, flexure, and dynamic topography
No full textA fundamental scientific question is, what controls the Earth's topography? Although the theoretical principles of isostasy, flexure, and dynamic topography are widely discussed, the parameters needed to apply these principles are frequently not available. Isostatic factors controlling lithospheric buoyancy are frequently uncertain and non-isostatic factors, such as lithospheric bending towards subduction zones and dynamic topography, are hard to distinguish. The question discussed here is whether a set of simple rules that relate topography to lithospheric structure in various tectonic environments can be deduced in a way that missing parameters can be approximated; or does each area behave differently, making generalizations problematic. We contribute to this issue analyzing the Asia–Africa–Arabia–Europe domain following a top-down strategy. We compile a new crustal thickness map and remove the contribution of the crust from the observed elevation. Then, the challenge is to interpret the residual topography in terms of mantle lithosphere buoyancy and dynamics. Based on systematic relationships between tectonic environments and factors controlling topography, we argue that crustal buoyancy and mantle lithospheric density can be approximated from available geological data and that regions near mantle upwelling or downwelling are easily identified by their extreme residual topography. Yet, even for other areas, calculating lithospheric thickness from residual topography is problematic, because distinguishing variations in mantle lithosphere thickness from sub-lithospheric dynamics is difficult. Fortunately, the area studied here provides an opportunity to examine this issue. Based on the conjunction between the Afar Plume and the mid-ocean ridge in the nearby Gulf of Aden and southern Red Sea, we constrain the maximal amplitude of dynamic topography to ~ 1 km. This estimate is based on a narrow definition of dynamic topography that only includes sub-lithospheric processes and using mid-ocean ridges as reference, where mantle lithosphere buoyancy is zero
Initiation of the Andean orogeny by lower mantle subduction
No full textThe Cordillera of the Andes is a double-vergent orogenic belt built up by thickening of South American plate crust. Several models provide plausible explanations for the evolution of the Andes, but the reason why shortening started at ∼50 Ma is still unclear. We explore the evolution of the subduction zone through time by restoring the position of the Nazca trench in an absolute reference frame, comparing its position with seismic tomography models and balancing the evolution of the subducting slab. Reconstructions show that the slab enters into the lower mantle at ∼50±10 Ma, and then progressed, moving horizontally at shallow lower mantle depth while thickening and folding in the transition zone. We test this evolutionary scenario by numerical models, which illustrate that compression in the upper plate intensifies once the slab is anchored in the lower mantle. We conclude that onset of significant shortening and crustal thickening in the Andes and its sustained action over tens of million years is related to the penetration of the slab into the lower mantle, producing a slowdown of lateral slab migration, and dragging the upper plate against the subduction zone by large-scale return flow
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