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|Title:||White matter hypoglycemic injury revealed by multiphoton microscopy in transgenic mice|
Macklin, Wendy B.
Goldberg, Mark P.
Cerebral ischemia -- Diagnosis
|Publisher:||Society for Neuroscience|
|Citation:||Valentino, M., Inoue, I., Macklin, W. B., Kirchhoff, F., & Goldberg, M. P. (2004). White matter hypoglycemic injury revealed by multiphoton microscopy in transgenic mice. (No. 1018.6). Washington DC.|
|Abstract:||Hypoglycemia is a common occurrence in diabetic patients. We investigated the time course of axon and oligodendrocyte structural injury in white matter exposed to hypoglycemic conditions. Acute coronal brain slices (400μm) including corpus callosum were prepared from transgenic mice with neuron specific expression of YFP controlled by the Thy1 promoter (Thy1-YFP; line 2.2; G Feng et al., Neuron 2000) or from oligodendrocyte-specific expression of GFP (PLP-EGFP; B.S Mallon et al., J. Neuroscience 2002) or dsRed (PLP-dsRed; F Kirchhoff et al) controlled by a proteolipid protein promoter. Perfused slices from Thy1-YFP mice were visualized using a multiphoton imaging system (Zeiss 510 NLO; upright microscope), which permitted high resolution time-lapse fluorescence imaging of intact axons deep in white matter slices (up to 120μm) with minimal photodamage. Transient glucose deprivation (45 min) caused delayed structural disruption of YFP-labeled axons, which appeared as beading, fragmentation, and loss of fluorescence intensity 30-60 min after restoration of glucose levels. Application of the AMPA/kainate antagonist, 30μM NBQX, reduced axonal injury even if started immediately following glucose deprivation. Multiphoton microscopy also allowed visualization of structural changes in oligodendrocytes in slices from PLP-transgenic mice. These results indicate that glucose deprivation causes delayed structural disruption in axons, mediated in part by activation of AMPA/kainate glutamate receptors. Transgenic expression of fluorescent proteins allows direct observation of cell-specific structural changes in living tissue.|
|Appears in Collections:||Scholarly Works - FacM&SPB|
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