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Project

In situ labeling of endogenous neuronal stem cells and the visualization of their recruitment and incorporation in the mouse brain with in vivo microMRI.

In healthy adult mice the major location with the production of neural precursor cells is 'the subventricular zone (SVZ' located near the later ventricles of the brain. From this region, the neural precursor cells migrate towards the olfactory bulb where they differentiate into new interneurons. This migration occurs in healthy animals along a specific pathway, the Rostral Migration Stream (RMS). In vivo examination of this normal migration is the first step towards possible manipulation of endogenous neural precursor cells for therapeutic purposes.For the in situ labeling of the precursor cells with a superparamagnetic contrast agent, we will evaluate and compare two new labeling techniques: 1)Direct injection of superparamagnetic iron oxide particles (SPIO's) into the lateral ventricle so that the SVZ cells after uptake of the SPIO's will be visible with in vivo MRI.2)Viral introduction of a MRI reportergen into the SVZ cells by which the cells will produce a superparamagnetic contrast agent and can be visualized by MRI.The successful design of a cellular imaging study with in vivo MRI depends on series of methodological evaluations and optimizations. The evaluation of both labeling techniques will be based on: 1) toxicity and effect on the cell proliferation and migration of the contrast agent and the reportergen, 2) the identification of the cell types by which the contrast agent is taken up/produced, 3) the visualization of the neuronal migration with in vivo MRI and 4) the visualization of incorporated new neurons in the olfactory bulb. The validation of the MRI studies will be done by immunohistochemistry.
Date:1 Jan 2008 →  31 Dec 2009
Keywords:MICRO MRI, STEM CELLS, IN SITU
Disciplines:Biochemistry and metabolism, Medical biochemistry and metabolism, Neurosciences, Biological and physiological psychology, Cognitive science and intelligent systems, Developmental psychology and ageing