Herein, we report a novel approach for neurotransmission modification in vivo by transplantation of stem cells engineered to take up the neurotransmitter dopamine (DA) efficiently through the action of the human dopamine transporter (hDAT). As a functional
test in mice, we used voluntary alcohol consumption, which is known to release DA in nucleus accumbens Bucladesine molecular weight (NAC), an event hypothesized to help maintain drug-seeking behavior. We reasoned that reducing extracellular DA levels, by engrafting into NAC DA-sequestering stem cells expressing hDAT, would alter alcohol intake.
Methods: We have generated a neural stem cell line stably expressing the hDAT. Uptake kinetics of DA were determined to select a clone for transplantation. These genetically
modified stem cells (or cells transfected with a construct lacking the hDAT sequence) were transplanted bilaterally into the NAC of wild-type mice trained to consume 10% alcohol in a two-bottle SIS3 price free-choice test for alcohol consumption. Alcohol intake was then ascertained for 1 week after transplantation, and brain sections through the NAC were examined for surviving grafted cells.
Results: Modified stem cells expressed hDAT and uptaken DA selectively via hDAT. Mice accustomed to drinking 10% ethanol by free choice reduced their alcohol consumption after being transplanted with hDAT-expressing stem cells. By contrast, control
stem cells lacked that effect. Histologic examination revealed surviving stem cells in the NAC of all engrafted brains.
Conclusions: Our findings represent proof of principle suggesting that genetically GDC-0973 manufacturer engineered stem cells can be useful for exploring the role of neurotransmitters (or other signaling molecules) in alcohol consumption and potentially in other aspects of brain function.”
“Aims: An optimal utilisation rate for palliative radiotherapy in newly diagnosed cancers will be useful in the planning and delivery of cancer services and has not been reported to date. The aim of this study was to estimate the proportion of new cases of cancer that should receive palliative radiotherapy as their first course of radiotherapy at some time during the course of their illness.
Materials and methods: A previously developed model depicting indications for radiotherapy was merged with Australian cancer epidemiological data and re-analysed to identify palliative or radical treatment end points. Palliative radiotherapy end points were further divided by treatment site. The optimal palliative radiotherapy utilisation rates were compared with actual radiotherapy utilisation data for newly diagnosed cancers.
Results: Fourteen per cent of all new cancer cases should optimally receive palliative radiotherapy as their first course of radiotherapy treatment.