Survival, neuron-like differentiation and functionality of mesenchymal stem cells in neurotoxic environment: the critical role of erythropoietin.

Mesenchymal stem cells (MSCs) can ameliorate symptoms in several neurodegenerative diseases. However, the toxic environment of a degenerating central nervous system (CNS) characterized by hypoxia, glutamate (Glu) excess and amyloid beta (Abeta) pathology may hamper the survival and regenerative/replacing capacities of engrafted stem cells. Indeed, human MSC (hMSC) exposed to hypoxia were disabled in (i) the capacity of their muscarinic receptors (mAChRs) to respond to acetylcholine (ACh) with a transient increase in intracellular [Ca(2+)], (ii) their capacity to metabolize Glu, reflected by a strong decrease in glutamine synthetase activity, and (iii) their survival on exposure to Glu. Cocultivation of MSC with PC12 cells expressing the amyloid precursor protein gene (APPsw-PC12) increased the release of IL-6 from MSC. HMSC exposed to erythropoietin (EPO) showed a cholinergic neuron-like phenotype reflected by increased cellular levels of choline acetyltransferase, ACh and mAChR. All their functional deficits observed under hypoxia, Glu exposure and APPsw-PC12 cocultivation were reversed by the application of EPO, which increased the expression of Wnt3a. EPO also enhanced the metabolism of Abeta in MSC by increasing their neprilysin content. Our data show that cholinergic neuron-like differentiation of MSC, their functionality and resistance to a neurotoxic environment is regulated and can be improved by EPO, highlighting its potential for optimizing cellular therapies of the CNS.

Simultaneous patch-clamp recording and calcium imaging in a rhythmically active neuronal network in the brainstem slice preparation from mouse.

Intracellular calcium signals are critical for modulation of neuronal function, and also for pathophysiological states during human neurodegenerative disease, such as Morbus Alzheimer and amyotrophic lateral sclerosis (ALS). We investigated intracellular calcium signals in motoneurones of the nucleus hypoglossus from the mouse, which were maintained in a functionally intact state of rhythmic, respiratory-related activity. Simultaneous patch-clamp recordings and calcium imaging demonstrated that rhythmic inspiratory-related clusters of action potential (AP) discharges are paralleled by calcium oscillations both in somatic and dendritic compartments. Calcium oscillations resulted primarily from the AP-induced opening of voltage-dependent calcium channels in the soma and dendrites. Dendritic calcium transients differed from somatic responses in their kinetics, amplitude, voltage dependence and regulation of basal calcium levels. Based on a combination of infrared differential interference contrast optics, microfluorimetric calcium imaging and electrophysiological patch-clamp recordings, our results demonstrate that the brainstem slice preparation is an attractive model system to study the integration and superposition of calcium signals in a functionally intact neuronal net.

Distribution of gap junctions in the chicken retina.

Coupling between cells of neuronal tissue can be due to electrical or chemical synapses. The molecular basis of an electrical synapse is the gap junction channel. Gap junctions have been found between neurones and glial cells, however, in some tissue their presence in the membranes of different cell types is still under discussion. In the retina of vertebrates, which is a true part of the CNS, the presence of gap junctions in the specialised glial cells of the retina, the Müller cells is not clear for chicken. Since these cells span the whole retina vertically, for some tasks, like spatial buffering of potassium, such gap junctions would not be required, in contrast to other parts of the CNS. The spatial buffering of potassium among others plays an important role in the propagation of excitation-depression waves in neuronal tissue, especially in the chicken retina. However, gap junctions could be involved in creating an electrical syncitium of glial cells, which might also contribute to excitation-depression wave propagation. In this paper we present an about complete screening of the presence of gap junctions in the chicken retina, including the proof that the Müller cells of this retina do not have gap junctions. This finding is discussed considering the highly specialised morphological structure of the Müller cells of the chicken retina, which have an extremely extended endfeet tree.

Achieving excellence in the management of accounts receivable.

Recent changes in healthcare reimbursement rules and practices have made the task of accounts receivable management a particularly demanding one for most financial managers. One multihospital system, after pursuing numerous strategies to reduce its accounts receivable with only marginal levels of success, launched a systemwide initiative to share both the positive and the negative accounts receivable management experiences of each department at each hospital in the system with all patient accounting staff. The objective of the initiative was to use the lessons learned from those experiences to attain excellence in accounts receivable management throughout the system. The ultimate success of the initiative is detailed in the following article.