Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING
JIB
BioConferenceLive

Real-Time Neuroimaging Technology Offers Glimpse Inside the Cell

By BiotechDaily International staff writers
Posted on 08 May 2014
Image: The micrograph shows a peripheral nerve, with the neuromuscular endplates stained in red. The nerve-cell mitochondria were imaged with a fluorescent redox sensor (green in the cytoplasm, yellow at the endplates) (Photo courtesy of M. Kerschensteiner and T. Misgeld).
Image: The micrograph shows a peripheral nerve, with the neuromuscular endplates stained in red. The nerve-cell mitochondria were imaged with a fluorescent redox sensor (green in the cytoplasm, yellow at the endplates) (Photo courtesy of M. Kerschensteiner and T. Misgeld).
Cutting-edge imaging technology provides insights into the role of redox signaling and reactive oxygen species in living neurons, in real time. German scientists have developed a new optical microscopy technique that provides insights into the role of oxidative stress in damaged as well as healthy nervous systems.

The study, performed by researchers from Technische Universität München (TUM; Germany) and the Ludwig-Maximilians-Universität München (LMU; Germany), was described in the April 2014 issue of the journal Nature Medicine.

Reactive oxygen species (ROS) are important intracellular signaling molecules, but their course of action is complicated: In low concentrations they control key aspects of cellular function and behavior, while at high concentrations they can cause oxidative stress, which damages DNA, organelles, and membranes. To examine how redox signaling unfolds in single cells and organelles in real-time, an innovative optical microscopy technique has been developed cooperatively by the teams of LMU Prof. Martin Kerschensteiner and TUM Prof. Thomas Misgeld, both investigators of the Munich Cluster for Systems Neurology (SyNergy).

“Our new optical approach allows us to visualize the redox state of important cellular organelles, mitochondria, in real time in living tissue,” Prof. Kerschensteiner said. In earlier studies, the investigators had obtained validation that oxidative damage of mitochondria might contribute to the destruction of axons in inflammatory diseases such as multiple sclerosis.

The new technology allows the scientists to monitor the oxidation states of individual mitochondria with high spatial and temporal resolution. Prof. Kerschensteiner explained the incentive behind the development of the technique. “Redox signals have important physiological functions, but can also cause damage, for example when present in high concentrations around immune cells.”

The scientists used redox-sensitive variants of the green fluorescent protein (GFP) as visualization tools. “By combining these with other biosensors and vital dyes, we were able to establish an approach that permits us to simultaneously monitor redox signals together with mitochondrial calcium currents, as well as changes in the electrical potential and the proton (pH) gradient across the mitochondrial membrane,” stated Prof. Misgeld.

The researchers have applied the technique to two experimental models, and have arrived at some unexpected insights. On the one hand, they have been able for the first time to study redox signal induction in response to neural damage—in this instance, spinal cord injury—in the mammalian nervous system. The observations revealed that severance of an axon results in a wave of oxidation of the mitochondria, which begins at the site of damage and is propagated along the fiber. Furthermore, a flood of calcium at the site of axonal resection was shown to be needed for the subsequent functional damage to mitochondria.

Quite possibly the most unexpected outcome of the new study was that the study’s first author, graduate student Michael Breckwoldt, was able to image for the first time, spontaneous contractions of mitochondria that are accompanied by a rapid shift in the redox state of the organelle.

Prof. Misgeld concluded, “This appears to be a fail-safe system that is activated in response to stress and temporarily attenuates mitochondrial activity. Under pathological conditions, the contractions are more prolonged and may become irreversible, and this can ultimately result in irreparable damage to the nerve process.”

Related Links:

Technische Universität München
Ludwig-Maximilians-Universität München



comments powered by Disqus

Channels

Genomics/Proteomics

view channel
Image: Microcomputed tomography images (top) and histology images (bottom) of the knees of mice fed a very high fat diet containing omega-3 fatty acid supplement (left) or only omega-6 fatty acids (right) after a knee injury. The omega-6 diet showed abnormal bone remodeling and calcified tissue formation in the joint (white arrow). The omega-6 diet also showed significant loss of cartilage (red staining, yellow arrowhead) and increased joint inflammation (Photo courtesy of Duke University).

Dietary Omega-3 Fatty Acids Moderate Severity of Osteoarthritis in a Mouse Model

Researchers working with an osteoarthritis (OA) obese mouse model found that the fat content of the animals' diet contributed more to the development or arrest of OA than did body weight.... Read more

Drug Discovery

view channel
Image: Molecular rendering of the crystal structure of parkin (Photo courtesy of Wikimedia Commons).

Cinnamon Feeding Blocks Development of Parkinson's Disease in Mouse Model

A team of neurological researchers has identified a molecular mechanism by which cinnamon acts to protect neurons from damage caused by Parkinson's disease (PD) in a mouse model of the syndrome.... Read more

Therapeutics

view channel

Vaccine Being Developed for Heart Disease Close to Reality

The world’s first vaccine for heart disease is becoming a possibility with researchers demonstrating significant arterial plaque reduction in concept testing in mice. Klaus Ley, MD, from the La Jolla Institute for Allergy and Immunology (LA Jolla, CA, USA), and a vascular immunology specialist, is leading the vaccine... Read more

Business

view channel

A Surge in IPOs Revitalize Investments for the Global Pharma and Biotech

Anti-infective drugs, oncology, and pharmaceutical contract laboratories attract the most investment up to now. The intensified private equity and venture capital (PEVC) deal activity in the global healthcare industry during the recession years, 2008–2010, witnessed a waning post-2010. However, the decline in deals... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.