Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/67533
Title: The disruption of mitochondrial axonal transport is an early event in neuroinflammation
Author: Errea Lorenzo, Oihana
Moreno, B.
González Franquesa, Alba
García-Roves, Pablo M. (Pablo Miguel)
Villoslada, Pablo
Keywords: Mitocondris
Inflamació
Estrès oxidatiu
Esclerosi múltiple
Mitochondria
Inflammation
Oxidative stress
Multiple sclerosis
Issue Date: 28-Aug-2015
Publisher: BioMed Central
Abstract: Background: in brain inflammatory diseases, axonal damage is one of the most critical steps in the cascade that leads to permanent disability. Thus, identifying the initial events triggered by inflammation or oxidative stress that provoke axonal damage is critical for the development of neuroprotective therapies. Energy depletion due to mitochondrial dysfunction has been postulated as an important step in the damage of axons. This prompted us to study the effects of acute inflammation and oxidative stress on the morphology, transport, and function of mitochondria in axons. Methods: mouse cerebellar slice cultures were challenged with either lipopolysaccharide (LPS) or hydrogen peroxide (H2O2) ex vivo for 24 h. Axonal mitochondrial morphology was evaluated by transmission electron microscopy (TEM) and mitochondrial transportation by time-lapse imaging. In addition, mitochondrial function in the cerebellar slice cultures was analyzed through high-resolution respirometry assays and quantification of adenosine triphosphate (ATP) production. Results: both conditions promoted an increase in the size and complexity of axonal itochondria evident in electron microscopy images, suggesting a compensatory response. Such compensation was reflected at the tissue level as increased respiratory activity of complexes I and IV and as a transient increase in ATP production in response to acute inflammation. Notably, time-lapse microscopy indicated that mitochondrial transport (mean velocity) was severely impaired in axons, increasing the proportion of stationary mitochondria in axons after LPS challenge. Indeed, the two challenges used produced different effects: inflammation mostly reducing retrograde transport and oxidative stress slightly enhancing retrograde transportation. Conclusions: neuroinflammation acutely impairs axonal mitochondrial transportation, which would promote an inappropriate delivery of energy throughout axons and, by this way, contribute to axonal damage. Thus, preserving axonal mitochondrial transport might represent a promising avenue to exploit as a therapeutic target for neuroprotection in brain inflammatory diseases like multiple sclerosis.
Note: Reproducció del document publicat a: http://dx.doi.org/10.1186/s12974-015-0375-8
It is part of: Journal of Neuroinflammation, 2015, vol. 12, p. 152
Related resource: http://dx.doi.org/10.1186/s12974-015-0375-8
URI: http://hdl.handle.net/2445/67533
ISSN: 1742-2094
Appears in Collections:Articles publicats en revistes (Ciències Fisiològiques)

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