前往化源商城

Journal of Neuroinflammation 2015-01-01

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

Oihana Errea, Beatriz Moreno, Alba Gonzalez-Franquesa, Pablo M Garcia-Roves, Pablo Villoslada

文献索引:J. Neuroinflammation 12 , 152, (2015)

全文:HTML全文

摘要

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.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.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.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.

相关化合物

结构式 名称/CAS号 全部文献
过氧化氢 结构式 过氧化氢
CAS:7722-84-1
腺嘌呤 结构式 腺嘌呤
CAS:73-24-5
二(2-羟乙基)亚氨基三(羟甲基)甲烷 结构式 二(2-羟乙基)亚氨基三(羟甲基)甲烷
CAS:6976-37-0
L-谷氨酰胺 结构式 L-谷氨酰胺
CAS:56-85-9
戊二醛 结构式 戊二醛
CAS:111-30-8
N,N,N',N'-四甲基对苯二胺 二盐酸盐 结构式 N,N,N',N'-四甲基对苯二胺 二盐酸盐
CAS:637-01-4
三(叔丁氧基)硅烷醇 结构式 三(叔丁氧基)硅烷醇
CAS:18166-43-3
碳酰氰-4-三氟甲氧基苯腙 结构式 碳酰氰-4-三氟甲氧基苯腙
CAS:370-86-5
鱼藤酮 结构式 鱼藤酮
CAS:83-79-4
吗啉乙磺酸 结构式 吗啉乙磺酸
CAS:4432-31-9