Morphological aspects of the hypothalamic-hypophyseal system

Summary The neural connections of various parts of the neurohypophysis of mammals (cats, dogs, rats) were investigated with the aid of the Golgi method, the aldehyde fuchsin technique (in combination with perfusion of the vascular system with India ink gelatine) and electron microscopy. The abundant supply of the palisade zone of the median eminence with thin axon terminals of the tubero-infundibular system is described. The independence of these terminals from the axons of the magnocellular neurosecretory system of the hypothalamus, which terminate in the caudal parts of the neurohypophysis, is evident. The clearcut differences between morphology and localization of the terminals of the parvi- and magnocellular neurosecretory systems at various levels of the neurohypophysis are described. The morphological aspects of the release of neural mediators in regions of these terminals are discussed.     

In vivo EPR tooth dosimetry for triage after a radiation event involving large populations

The management of radiation injuries following a catastrophic event where large numbers of people may have been exposed to life-threatening doses of ionizing radiation will rely critically on the availability and use of suitable biodosimetry methods. In vivo electron paramagnetic resonance (EPR) tooth dosimetry has a number of valuable and unique characteristics and capabilities that may help enable effective triage. We have produced a prototype of a deployable EPR tooth dosimeter and tested it in several in vitro and in vivo studies to characterize the performance and utility at the state of the art. This report focuses on recent advances in the technology, which strengthen the evidence that in vivo EPR tooth dosimetry can provide practical, accurate, and rapid measurements in the context of its intended use to help triage victims in the event of an improvised nuclear device. These advances provide evidence that the signal is stable, accurate to within 0.5 Gy, and can be successfully carried out in vivo. The stability over time of the radiation-induced EPR signal from whole teeth was measured to confirm its long-term stability and better characterize signal behavior in the hours following irradiation. Dosimetry measurements were taken for five pairs of natural human upper central incisors mounted within a simple anatomic mouth model that demonstrates the ability to achieve 0.5 Gy standard error of inverse dose prediction. An assessment of the use of intact upper incisors for dose estimation and screening was performed with volunteer subjects who have not been exposed to significant levels of ionizing radiation and patients who have undergone total body irradiation as part of bone marrow transplant procedures. Based on these and previous evaluations of the performance and use of the in vivo tooth dosimetry system, it is concluded that this system could be a very valuable resource to aid in the management of a massive radiological event.     

Role of Dopamine D2/D3 Receptors in Development,Plasticity, and Neuroprotection in Human iPSC-Derived Midbrain Dopaminergic Neurons

The role of dopamine D2 and D3 receptors (D2R/D3R), located on midbrain dopaminergic (DA) neurons, in the regulation of DA synthesis and release and in DA neuron homeostasis has been extensively investigated in rodent animal models. By contrast, the properties of D2R/D3R in human DA neurons have not been elucidated yet. On this line, the use of human-induced pluripotent stem cells (hiPSCs) for producing any types of cells has offered the innovative opportunity for investigating the human neuronal phenotypes at the molecular levels. In the present study, hiPSCs generated from human dermal fibroblasts were used to produce midbrain DA (mDA) neurons, expressing the proper set of genes and proteins typical of authentic, terminally differentiated DA neurons. In this model, the expression and the functional properties of the human D2R/D3R were investigated with a combination of biochemical and functional techniques. We observed that in hiPSC-derived mDA neurons, the activation of D2R/D3R promotes the proliferation of neuronal progenitor cells. In addition, we found that D2R/D3R activation inhibits nicotine-stimulated DA release and exerts neurotrophic effects on mDA neurons that likely occur via the activation of PI3K-dependent mechanisms. Furthermore, D2R/D3R stimulation counteracts both the aggregation of alpha-synuclein induced by glucose deprivation and the associated neuronal damage affecting both the soma and the dendrites of mDA neurons. Taken together, these data point to the D2R/D3R-related signaling events as a biochemical pathway crucial for supporting both neuronal development and survival and protection of human DA neurons.