Developmental loss of NT-3 in vivo results in reduced levels of myelin-specific proteins

February 01, 2008

Glia. 2008 Feb;56(3):306-17.

Developmental loss of NT-3 in vivo results in reduced levels of myelin-specific proteins, a reduced extent of myelination and increased apoptosis of Schwann cells.

Woolley AG, Tait KJ, Hurren BJ, Fisher L, Sheard PW, Duxson MJ.

Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.

This work investigates the role of NT-3 in peripheral myelination. Recent articles, based in vitro, propose that NT-3 acting through its high-affinity receptor TrkC may act to inhibit myelin formation by enhancing Schwann cell motility and/or migration. Here, we investigate this hypothesis in vivo by examining myelination formation in NT-3 mutant mice. On the day of birth, soon after the onset of myelination, axons showed normal ensheathment by Schwann cells, no change in the proportion of axons which had begun to myelinate, and no change in either myelin thickness or number of myelin lamellae. However in postnatal day 21 mice, when myelination is substantially complete, we observed an unexpected reduction in mRNA and protein levels for MAG and P(0), and in myelin thickness. This is the opposite result to that predicted from previous in vitro studies, where removal of an inhibitory NT-3 signal would have been expected to enhance myelination. These results suggest that, in vivo, the importance of NT-3 as a major support factor for Schwann cells (Meier et al., (1999) J Neurosci 19:3847-3859) over-rides its potential role as an myelin inhibitor, with the net effect that loss of NT-3 results in degradation of Schwann cell functions, including myelination. In support of this idea, Schwann cells of NT-3 null mutants showed increased expression of activated caspase-3. Finally, we observed significant reduction in width of the Schwann cell periaxonal collar in NT-3 mutant animals suggesting that loss of NT-3 and resulting reduction in MAG levels may alter signaling at the axon-glial interface.

Bone Marrow Cell Transplants Help Nerve Regeneration

December 05, 2007

ScienceDaily (Dec. 5, 2007) — A study carried out by researchers at the Kyoto University School of Medicine has shown that when transplanted bone marrow cells (BMCs) containing adult stem cells are protected by a 15mm silicon tube and nourished with bio-engineered materials, they successfully help regenerate damaged nerves. The research may provide an important step in developing artificial nerves.

"We focused on the vascular and neurochemical environment within the tube," said Tomoyuki Yamakawa, MD, the study's lead author. "We thought that BMCs containing adult stem cells, with the potential to differentiate into bone, cartilage, fat, muscle, or neuronal cells, could survive by obtaining oxygen and nutrients, with the result that rates of cell differentiation and regeneration would improve."

Nourished with bioengineered additives, such as growth factors and cell adhesion molecules, the BMCs after 24 weeks differentiated into cells with characteristics of Schwann cells -- a variety of neural cell that provides the insulating myelin around the axons of peripheral nerve cells. The new cells successfully regenerated axons and extended their growth farther across nerve cell gaps toward damaged nerve stumps, with healthier vascularity.

"The differentiated cells, similar to Schwann cells, contributed significantly to the promotion of axon regeneration through the tube," explained Yamakawa. "This success may be a further step in developing artificial nerves."

Read more of Bone Marrow Cell Transplants Help Nerve Regeneration

Silk 'could help repair nerves'

July 14, 2006

Silk may be able to help repair damaged nerves, according to scientists.

The UK researchers have shown how nerve cells can grow along bundles of a special fibre, which has properties similar to spider silk.

They hope the silk will encourage cell re-growth across severed nerves, possibly even in damaged spinal cords. [BBC]

New Roles For Growth Factors: Enticing Nerve Cells To Muscles

June 17, 2006

During embryonic development, nerve cells hesitantly extend tentacle-like protrusions called axons that sniff their way through a labyrinth of attractive and repulsive chemical cues that guide them to their target.

While several recent studies discovered molecules that repel motor neuron axons from incorrect targets in the limb, scientists at the Salk Institute for Biological Studies have identified a molecule, known as FGF, that actively lures growing axons closer to the right destination. Their findings appear in the June 15 issue of Neuron.

"The most important aspect of our finding is not necessarily that we finally nailed the growth factor FGF as the molecule that guides a specific subgroup of motor neurons to connect to the muscles that line our spine and neck," says senior author Samuel Pfaff, Ph.D., a professor in the Gene Expression Laboratory, "but that piece by piece, we are uncovering general principles that ensure that the developing nervous system establishes proper neuronal connections." [Science Daily]