Pervasive Axonal Transport Deficits in Multiple Sclerosis Models

نویسندگان

  • Catherine Diamante Sorbara
  • Naomi Elizabeth Wagner
  • Anne Ladwig
  • Ivana Nikić
  • Doron Merkler
  • Tatjana Kleele
  • Petar Marinković
  • Ronald Naumann
  • Leanne Godinho
  • Florence Martine Bareyre
  • Derron Bishop
  • Thomas Misgeld
  • Martin Kerschensteiner
چکیده

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.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Please Mind the Gap: Axonal Transport Deficits in Multiple Sclerosis Neurodegeneration

In this issue, Sorbara et al. (2014) demonstrate that axonal transport impairment is an early feature of neurodegeneration in multiple sclerosis models. This transport deficit is reversible by anti-inflammatory intervention but, if untreated, can contribute to late-stage axonal dystrophy.

متن کامل

Axonal transport deficits and degeneration can evolve independently in mouse models of amyotrophic lateral sclerosis.

Axonal transport deficits have been reported in many neurodegenerative conditions and are widely assumed to be an immediate causative step of axon and synapse loss. By imaging changes in axonal morphology and organelle transport over time in several animal models of amyotrophic lateral sclerosis (ALS), we now find that deficits in axonal transport of organelles (mitochondria, endosomes) and axo...

متن کامل

Axonal transport defects are a common phenotype in Drosophila models of ALS

Amyotrophic lateral sclerosis (ALS) is characterized by the degeneration of motor neurons resulting in a catastrophic loss of motor function. Current therapies are severely limited owing to a poor mechanistic understanding of the pathobiology. Mutations in a large number of genes have now been linked to ALS, including SOD1, TARDBP (TDP-43), FUS and C9orf72. Functional analyses of these genes an...

متن کامل

Relationship between Mitochondrial Dysfunction and Multiple Sclerosis: A Review Study

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system that inflammation, demyelination, oligodendrocyte loss, gliosis, axonal injury and neurodegeneration are the main histopathological hallmarks of the disease. Although MS was classically thought as a demyelinating disease, but axonal injury occurs commonly in acute inflammatory lesions. In MS mi...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Neuron

دوره 84  شماره 

صفحات  -

تاریخ انتشار 2014