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eebo-0147

Philips, Thomas, --- Great Britain --- Turkey --- History --- Foreign relations

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ALS is a motor neuron degenerative disease for which there is currently no treatment available. Glial cells that surround motor neurons become reactive and contribute to the selective death of these cells, ie motor neuron diseae is non-cell autonomous. Although there is some progress in our understanding how glial cells contribute to motor neuron degeneration, this reaction is still poorly understood. Therefore, the goal of this study is to explore the contribution of four different glial subtypes to motor neuron loss. We assessed the role of microglial cells, astrocytes, NG2 glial progenitor cells and oligodendrocytes. Microglial cells and astrocytes become reactive as disease progresses. The microglial reaction comprises three different cell subtypes: mature microglia, macrophages and myeloid precursor cells. Microgliosis is mediated by proliferation, rather than recruitment of myeloid progenitor cells from the peripheral blood stream. The proliferating microglia do not seem to contribute to motor neuron degeneration, as ablation of proliferating microglia did not influence motor neuron loss. In fact the microglial reaction is a double edged sword: providing both neuroprotective as well as neurotoxic activity at later disease stages. Therapeutic strategies should therefore aim to promote the neuroprotective activity while inhibiting the neurotoxic actions of these cells. The astroglial reaction is not mediated by proliferation. We studied whether glial progenitor cells like NG2 glial progenitor cells and ependymal cells contributed to the generation of reactive astrocytes. Both glial cells did not contribute to astrogliogenesis, indicating that astrogliosis is rather mediated by activation of resident astrocytes than by recruitment form a progenitor pool. The role of oligodendrocytes in motor neuron degeneration is largely unexplored. We found that these cells become dysmorphic and die at later disease stages. Their cell number does not change as these cells are replenished by newly generated oligodendrocytes which are derived from NG2 glial progenitor cells. These newly derived oligodendrocytes are dysfunctional however, as they produce less myelin and provide less trophic support to the motor neurons. As glial cells contribute to the loss of motor neurons, it is of interest to modulate their contribution to motor neuron loss in order to delay disease and improve survival of ALS patients.

Academic collection --- Theses

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Bible. --- Criticism, interpretation, etc --- 226.6 --- Handelingen der apostelen. Akten van de apostelen --- Criticism, interpretation, etc. --- Festschrift - Libri Amicorum --- Acts (Book of the New Testament) --- Acts of the Apostles --- Chongdo haengjŏn --- Sado haengjŏn

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