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Testosterone for nerve fibre repair (2017-01-25)

What is involved in the spontaneous regeneration of the myelin sheath surrounding nerve fibres? Researchers have discovered, in mice, the unexpected regenerative role of testosterone in this process.

Transmission electron micrograph of a myelinated axon. The myelin layer (concentric) surrounds the axon of a neurone, showing cytoplasmathic organs inside. Generated and deposited into the public domain by the Electron Microscopy Facility at Trinity College.

This could be a factor in the progression of demyelinating diseases, such as multiple sclerosis, which can present differently in women and men, and heralds new therapeutic opportunities.

The myelin sheath allows the rapid transmission of information between the brain or spinal cord and the rest of the body.
Myelin may be targeted by conditions known as demyelinating diseases, such as multiple sclerosis or injuries that lead to its destruction.

These diseases disrupt neurotransmission, leading to various symptoms including paralysis.
Repair mechanisms then come into play, and bring about myelin regeneration and resolution of symptoms.
This regenerative process is erratic, for reasons that are still largely unknown. This question was analysed by the research team “Myelination and Myelin Repair” in Unit 1195, “Neuroprotective, Neuroregenerative and Remyelinating Small Molecules” (Inserm/Paris-Sud University).

In this study, the researchers present evidence of the unexpected central role of the well-known male sex hormone, testosterone, and of its receptor, the androgen receptor, in spontaneous myelin repair.

“Testosterone promotes the production of myelin by the cells that synthesise it in the central nervous system, in order to repair the sheath, which is essential to the transmission of nerve impulses,” explains Elisabeth Traiffort, Inserm Research Director.

In the absence of testes and hence of the hormone, testosterone, that these organs produce, the spontaneous myelin repair process is disrupted in mice.

Indeed, the maturation of cells specialised in myelin synthesis, known as oligodendrocytes, is defective. The researchers also showed that control of this maturation, provided by astrocytes, another type of cell with an important role in repair, is what is compromised.

But why testosterone? Returning to the origins of this hormone, it turns out, surprisingly, that the androgen receptor that enables testosterone to act appeared at the same time as myelin, very late in the evolution of gnathostomes (vertebrates with jaws). According to the researchers, this would explain their very strong association in the myelination process.

For more information
Unexpected central role of the androgen receptor in the spontaneous regeneration of myelin

Institut national de la santé et de la recherche médicale