c-Jun activation in Schwann cells protects against loss of sensory axons in inherited neuropathy

Janina Hantke; Lucy Carty; Laura J. Wagstaff; Mark Turmaine; Daniel K. Wilton; Susanne Quintes; Martin Koltzenburg; Frank Baas; Rhona Mirsky; Kristján R. Jessen

doi:10.1093/brain/awu257

Schwann cells induce sprouting in motor and sensory axons in the adult rat spinal cord

Journal of Neuroscience ◽

10.1523/jneurosci.14-07-04050.1994 ◽

1994 ◽

Vol 14 (7) ◽

pp. 4050-4063 ◽

Cited By ~ 162

Author(s):

Y Li ◽

G Raisman

Keyword(s):

Spinal Cord ◽

Schwann Cells ◽

Rat Spinal Cord ◽

Adult Rat ◽

Sensory Axons ◽

Adult Rat Spinal Cord

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Evidence that sensory axons are mitogenic for Schwann cells

Nature ◽

10.1038/256662a0 ◽

1975 ◽

Vol 256 (5519) ◽

pp. 662-664 ◽

Cited By ~ 291

Author(s):

PATRICK M. WOOD ◽

RICHARD P. BUNGE

Keyword(s):

Schwann Cells ◽

Sensory Axons

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Heterophilic Binding of L1 on Unmyelinated Sensory Axons Mediates Schwann Cell Adhesion and Is Required for Axonal Survival

The Journal of Cell Biology ◽

10.1083/jcb.146.5.1173 ◽

1999 ◽

Vol 146 (5) ◽

pp. 1173-1184 ◽

Cited By ~ 73

Author(s):

C.A. Haney ◽

Z. Sahenk ◽

C. Li ◽

V.P. Lemmon ◽

J. Roder ◽

...

Keyword(s):

Nervous System ◽

Schwann Cell ◽

Schwann Cells ◽

Sensory Nerves ◽

Sensory Function ◽

Trophic Effect ◽

Unmyelinated Fibers ◽

Sensory Axons ◽

Unmyelinated Axons ◽

Deficient Mice

This study investigated the function of the adhesion molecule L1 in unmyelinated fibers of the peripheral nervous system (PNS) by analysis of L1- deficient mice. We demonstrate that L1 is present on axons and Schwann cells of sensory unmyelinated fibers, but only on Schwann cells of sympathetic unmyelinated fibers. In L1-deficient sensory nerves, Schwann cells formed but failed to retain normal axonal ensheathment. L1-deficient mice had reduced sensory function and loss of unmyelinated axons, while sympathetic unmyelinated axons appeared normal. In nerve transplant studies, loss of axonal-L1, but not Schwann cell-L1, reproduced the L1-deficient phenotype. These data establish that heterophilic axonal-L1 interactions mediate adhesion between unmyelinated sensory axons and Schwann cells, stabilize the polarization of Schwann cell surface membranes, and mediate a trophic effect that assures axonal survival.

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Intrathecal gene therapy rescues a model of demyelinating peripheral neuropathy

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1522202113 ◽

2016 ◽

Vol 113 (17) ◽

pp. E2421-E2429 ◽

Cited By ~ 34

Author(s):

Alexia Kagiava ◽

Irene Sargiannidou ◽

George Theophilidis ◽

Christos Karaiskos ◽

Jan Richter ◽

...

Keyword(s):

Gene Therapy ◽

Peripheral Neuropathy ◽

Schwann Cells ◽

Peripheral Nerves ◽

Lentiviral Vector ◽

Intrathecal Injection ◽

Specific Expression ◽

Inherited Neuropathy ◽

Spinal Roots ◽

Demyelinating Peripheral Neuropathy

Inherited demyelinating peripheral neuropathies are progressive incurable diseases without effective treatment. To develop a gene therapy approach targeting myelinating Schwann cells that can be translatable, we delivered a lentiviral vector using a single lumbar intrathecal injection and a myelin-specific promoter. The human gene of interest, GJB1, which is mutated in X-linked Charcot–Marie–Tooth Disease (CMT1X), was delivered intrathecally into adult Gjb1-null mice, a genetically authentic model of CMT1X that develops a demyelinating peripheral neuropathy. We obtained widespread, stable, and cell-specific expression of connexin32 in up to 50% of Schwann cells in multiple lumbar spinal roots and peripheral nerves. Behavioral and electrophysiological analysis revealed significantly improved motor performance, quadriceps muscle contractility, and sciatic nerve conduction velocities. Furthermore, treated mice exhibited reduced numbers of demyelinated and remyelinated fibers and fewer inflammatory cells in lumbar motor roots, as well as in the femoral motor and sciatic nerves. This study demonstrates that a single intrathecal lentiviral gene delivery can lead to Schwann cell-specific expression in spinal roots extending to multiple peripheral nerves. This clinically relevant approach improves the phenotype of an inherited neuropathy mouse model and provides proof of principle for treating inherited demyelinating neuropathies.

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Ultrastructure of Giant Mitochondria and Their Inclusions in Schwann Cells of Bovine Splenic Nerve

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100050986 ◽

1974 ◽

Vol 32 ◽

pp. 194-195

Author(s):

Å. Thureson-Klein

Keyword(s):

Schwann Cells ◽

Cell Organelles ◽

Giant Mitochondria ◽

Matrix Density ◽

Physiological Conditions ◽

Unmyelinated Axons ◽

Internal Structures ◽

Structural Abnormalities ◽

Cytotoxic Compounds ◽

Cell Components

Giant mitochondria of various shapes and with different internal structures and matrix density have been observed in a great number of tissues including nerves. In most instances, the presence of giant mitochondria has been associated with a known disease or with abnormal physiological conditions such as anoxia or exposure to cytotoxic compounds. In these cases degenerative changes occurred in other cell organelles and, therefore the giant mitochondria also were believed to be induced structural abnormalities.Schwann cells ensheating unmyelinated axons of bovine splenic nerve regularly contain giant mitochondria in addition to the conventional smaller type (Fig. 1). These nerves come from healthy inspected animals presumed not to have been exposed to noxious agents. As there are no drastic changes in the small mitochondria and because other cell components also appear reasonably well preserved, it is believed that the giant mitochondria are normally present jin vivo and have not formed as a post-mortem artifact.

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Human Neurofibromas in Co-Culture with Mouse Neurons

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100053632 ◽

1982 ◽

Vol 40 ◽

pp. 194-195

Author(s):

R.L. Martuza ◽

T. Liszczak ◽

A. Okun ◽

T-Y Wang

Keyword(s):

Schwann Cell ◽

Schwann Cells ◽

Genetic Disorder ◽

Cranial Nerves ◽

Sympathetic Nerves ◽

Acoustic Neuromas ◽

Spinal Roots ◽

Neural Crest Origin ◽

Multiple Abnormalities ◽

Other Neoplasms

Neurofibromatosis (NF) is an autosomal dominant genetic disorder with a prevalence of 1/3,000 births. The NF mutation causes multiple abnormalities of various cells of neural crest origin. Schwann cell tumors (neurofibromas, acoustic neuromas) are the most common feature of neurofibromatosis although meningiomas, gliomas, and other neoplasms may be seen. The schwann cell tumors commonly develop from the schwann cells associated with sensory or sympathetic nerves or their ganglia. Schwann cell tumors on ventral spinal roots or motor cranial nerves are much less common. Since the sensory neuron membrane is known to contain a mitogenic factor for schwann cells, we have postulated that neurofibromatosis may be due to an abnormal interaction between the nerve and the schwann cell and that this interaction may be hormonally modulated. To test this possibility a system has been developed in which an enriched schwannoma cell culture can be obtained and co-cultured with pure neurons.

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