Enhanced tonic GABAA inhibition in typical absence epilepsy

The cellular mechanisms underlying typical absence seizures, which characterize various idiopathic generalized epilepsies, are not fully understood, but impaired GABAergic inhibition remains an attractive hypothesis. In contrast, we show here that extrasynaptic GABAA receptor–dependent ‘tonic’ inhibition is increased in thalamocortical neurons from diverse genetic and pharmacological models of absence seizures. Increased tonic inhibition is due to compromised GABA uptake by the GABA transporter GAT–1 in the genetic models tested, and GAT–1 is critical in governing seizure genesis. Extrasynaptic GABAA receptors are a requirement for seizures in two of the best characterized models of absence epilepsy, and the selective activation of thalamic extrasynaptic GABAA receptors is sufficient to elicit both electrographic and behavioural correlates of seizures in normal animals. These results identify an apparently common cellular pathology in typical absence seizures that may have epileptogenic significance, and highlight novel therapeutic targets for the treatment of absence epilepsy.peer-reviewe

P2X7 receptor: Death or life?

The P2X7 plasma membrane receptor is an intriguing molecule that is endowed with the ability to kill cells, as well as to activate many responses and even stimulate proliferation. Here, the authors give an overview on the multiplicity and complexity of P2X7-mediated responses, discussing recent information on this receptor. Particular attention has been paid to early and late signs of apoptosis and necrosis linked to activation of the receptor and to the emerging field of P2X7 function in carcinogenesis

Prevention and reversal of renal allograft rejection by antibody against CD45RB

REJECTION continues to be the single largest impediment to successful organ transplantation(1). Antilymphocyte globulin, which contains antibodies that react with the leukocyte common antigen known as CD45 (refs 2-6), has proved to be one of the most effective agents for preventing rejection. We have shown earlier that a monoclonal antibody directed against the RB isoform of CD45 substantially inhibits the alloreactivity of human CD4(+) lymphocytes in vitro(7). Here we investigate whether CD45RB could be an appropriate target for preventing renal allograft rejection in mice. Mice treated with two injections of a monoclonal antibody (MB23G2) (ref. 8) raised against CD45RB protein all survived and had normal renal function. Furthermore, this antibody reversed acute rejection when therapy was delayed until day 4, and the mice survived for their natural lifespan. The immunosuppression achieved may find application in the prevention and treatment of transplant rejection in man

Farside explorer: Unique science from a mission to the farside of the moon

Farside Explorer is a proposed Cosmic Vision medium-size mission to the farside of theMoon consisting of two landers and an instrumented relay satellite. The farside of the Moon is a unique scientific platform in that it is shielded from terrestrial radio-frequency interference, it recorded the primary differentiation and evolution of the Moon, it can be continuously monitored from the Earth–Moon L2 Lagrange point, and there is a complete lack of reflected solar illumination from the Earth. Farside Explorer will exploit these properties and make the first radio-astronomy measurements from the most radio-quiet region of near-Earth space, determine the internal structure and thermal evolution of the Moon, from crust to core, and quantify impact hazards in near-Earth space by the measurement of flashes generated by impact events. The Farside Explorer flight system includes two identical solarpowered landers and a science/telecommunications relay satellite to be placed in a halo orbit about the Earth–Moon L2 Lagrange point. One lander would explore the largest and oldest recognized impact basin in the Solar System—the South Pole–Aitken basin—and the other would investigate the primordial highlands crust. Radio astronomy, geophysical, and geochemical instruments would be deployed on the surface, and the relay satellite would continuously monitor the surface for impact events.Space EngineeringAerospace Engineerin