Axonal transport problems in progression

Sorbara CD, Wagner NE, Ladwig A, Nikić I, Merkler D, Kleele T, Marinković P, Naumann R, Godinho L, Bareyre FM, Bishop D, Misgeld T, Kerschensteiner M.Pervasive Axonal Transport Deficits in Multiple Sclerosis Models.Neuron. 2014. pii: S0896-6273(14)01006-X.

Impaired axonal transport can contribute to axon degeneration and has been described in many neurodegenerative diseases. Multiple sclerosis (MS) is a common neuroinflammatory disease, which is characterized by progressive axon degeneration-whether, when, and how axonal transport is affected in this condition is unknown. Here we used in vivo two-photon imaging to directly assay transport of organelles and the stability of microtubule tracks in individual spinal axons in mouse models of MS. We found widespread transport deficits, which preceded structural alterations of axons, cargos, or microtubules and could be reversed by acute anti-inflammatory interventions or redox scavenging. Our study shows that acute neuroinflammation induces a pervasive state of reversible axonal dysfunction, which coincides with acute disease symptoms. Moreover, perpetuated transport dysfunction, as we found in a model of progressive MS, led to reduced distal organelle supply and could thus contribute to axonal dystrophy in advanced stages of the disease.

Axoplasmic transport, also called axonal transport, is a cellular process responsible for movement of mitochondria, lipids, synaptic vesicles, proteins, and other cell parts (i.e. organelles) to and from a neuron’s cell body, through the cytoplasm of its axon (the axoplasm).Axons, which can be 1,000 or 10,000 times the length of the cell body. Axonal transport proteins from the nucleus down the axon is also responsible for moving molecules destined for degradation from the axon back to the cell body, where they are broken down by. Movement toward the cell body is called retrograde transport and movement toward the synapse is called anterograde transport. In the animal model of MS they find that disease is associated with a deficit in transport and this precedes problems and is subject the the actions of treatment. This was reversible, but in more chronic disease they found that organelle, like mitochondria that are the cells power houses, transport is reduced and this could be part of the pathological problem and targeted to improve nerve function 

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