当前位置： SCI文献检索 > Journal of Neuroinflammation期刊下所有文献 > The disruption of mitochondrial axonal transport is an early event in neuroinflammation.

The disruption of mitochondrial axonal transport is an early event in neuroinflammation.

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 mitochondria 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.

journal_name

J Neuroinflammation

journal_title

Journal of neuroinflammation

authors

Errea O,Moreno B,Gonzalez-Franquesa A,Garcia-Roves PM,Villoslada P

doi

10.1186/s12974-015-0375-8

subject

Has Abstract

pub_date

2015-08-28 00:00:00

pages

152

issn

1742-2094

pii

10.1186/s12974-015-0375-8

journal_volume

pub_type

杂志文章

在线工具

The disruption of mitochondrial axonal transport is an early event in neuroinflammation.