Carmichael’s Concise Review
Coming Events 2016
EPMA 2016: Electron Probe Microanalysis
Topical Conference May 16–19, 2016 Madison, WI
www.microbeamanalysis.org/topicalconferences/ epma-2016-1/epma-2016
APMC11 – 11th Asia-Pacifi c Microscopy
Conference May 23–27, 2016 Phuket, Thailand
www.apmc11.org
EBSD 2016: Electron Backscatter
Diffraction Topical Conference May 24–26, 2016 Tuscaloosa, AL
www.microbeamanalysis.org/topical-conferences/ ebsd-2016/welcome
Inter/Micro: 68th Annual Applied
Microscopy Conference June 6–10, 2016 Chicago, IL
www.mcri.org
43rd MSC Annual Meeting June 7–10, 2016 Edmonton, Alberta
http://conference2016.msc-smc.org
Microscopy & Microanalysis 2016 July 24–28, 2016 Columbus, OH
www.microscopy.org
65th X-ray Analysis Conference August, 1–5, 2016 Rosemont, IL
www.dxcicdd.com
European Microscopy Congress August 28–September 2, 2016 Lyon, France
http://emc2016.fr
2017
Microscopy & Microanalysis 2017 July 23–27, 2017 St. Louis, MO
www.microscopy.org 2018
Microscopy & Microanalysis 2018 August 5–9, 2018 Baltimore, MD
www.microscopy.org
2019
Microscopy & Microanalysis 2019 August 4–8, 2019 Portland, OR
www.microscopy.org 2020
Microscopy & Microanalysis 2020 August 2–6, 2020 Milwaukee, WI
www.microscopy.org
More Meetings and Courses Check the complete calendar near the back of this magazine.
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Figure 1 : 3D EM reconstruction of the CA1 hippocampal brain region from an APP/PS1 (Alzheimer’s Disease model) transgenic mouse. Left: Standard TEM images like the one presented were collected from serial thin sections, stacked, aligned, and visualized using reconstruction software. Right: The resulting 3D image of an individual neuropil (blue) allows for a detailed observation of mitochondria morphology (red) within the neuropil indicating presence of MOAS. Scale bar = 1.0 µm.
doi: 10.1017/S1551929516000304 2016 May
Alzheimer’s disease (AD) presently aff ects more than 5 million Americans with numbers expected to grow. T e specifi c molecular mechanisms of AD are still under investigation thereby hindering the development of eff ective therapies. Progressive memory decline is associated with synaptic loss and neuronal cell death. Signifi cant hypometabolic changes can be detected early in AD patients, which suggests that abnormal energy metabolism underlies disease etiology. Mitochondria are dynamic organelles that constantly move within the cell and undergo fi ssion and fusion (collectively termed “mitochondrial dynamics”). Such changes are important for proper responses to cellular energy demands. Fidelity of mitochondrial dynamics is especially important for the proper functioning of neurons where mitochondria need to travel over long distances to provide energy for distant parts of axons. Excessive mitochondrial fragmentation was observed in brain tissue of transgenic animal models of AD and postmortem brain from AD patients. T ese data suggested modulation of mitochondrial dynamics could represent novel therapeutic strategies for AD treatment. However, the understanding of the molecular mechanisms and details involved in the changes in mitochondrial morphology are incomplete and are hindered by the lack of tools that could study these dynamic changes in intact brain tissue. In an elegant study, Zhang, Salisbury, Trushina et al. used three-dimensional electron microscopy (3D EM) to look for changes in mitochondria in the brain of patients and animal models of AD. Using well-accepted transgenic mouse models of AD (and non-transgenic littermates as controls) Zhang et al. noticed diff erences in mitochondrial morphology in the CA1 hippocampus using standard transmission electron microscopy and super-resolution immunofl uorescence. In order to better visualize these morphological changes they used 3D EM that provided a “virtual” specimen thickness of 0.9 μ m to 3.6 μ m in 10 to 40 consecutive serial sections that were stacked, aligned, and reconstructed using 3D reconstruction soſt ware ( Figure 1 ). T ey identifi ed a previously unknown mitochondrial fi ssion arrest phenotype that results in elongated intercon- nected organelles that they dubbed “mitochondria-on-a-string” (MOAS). T eir data suggested that MOAS formation may occur at the fi nal stages of the fi ssion process and was not associated
Visualizing Changes in Mitochondria in Alzheimer’s Disease
Stephen W. Carmichael Mayo Clinic , Rochester , MN 55905
carmichael.stephen@
mayo.edu
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