Unexpected central role of the androgen receptor in the spontaneous regeneration of myelin.
Lost myelin can be replaced after injury or during demyelinating diseases in a regenerative process called remyelination. In the central nervous system (CNS), the myelin sheaths, which protect axons and allow the fast propagation of electrical impulses, are produced by oligodendrocytes. The abundance and widespread distribution of oligodendrocyte progenitors (OPs) within the adult CNS account for this remarkable regenerative potential. Here, we report a key role for the male gonad, testosterone, and androgen receptor (AR) in CNS remyelination. After lysolecithin-induced demyelination of the male mouse ventral spinal cord white matter, the recruitment of glial fibrillary acidic protein-expressing astrocytes was compromised in the absence of testes and testosterone signaling via AR. Concomitantly, the differentiation of OPs into oligodendrocytes forming myelin basic protein (MBP)+ and proteolipid protein-positive myelin was impaired. Instead, in the absence of astrocytes, axons were remyelinated by protein zero (P0)+ and peripheral myelin protein 22-kDa (PMP22)+ myelin, normally only produced by Schwann cells in the peripheral nervous system. Thus, testosterone favors astrocyte recruitment and spontaneous oligodendrocyte-mediated remyelination. This finding may have important implications for demyelinating diseases, psychiatric disorders, and cognitive aging. The testosterone dependency of CNS oligodendrocyte remyelination may have roots in the evolutionary history of the AR, because the receptor has evolved from an ancestral 3-ketosteroid receptor through gene duplication at the time when myelin appeared in jawed vertebrates.
['Bielecki|Bartosz|B|', 'Mattern|Claudia|C|', 'Ghoumari|Abdel M|AM|', 'Javaid|Sumaira|S|', 'Smietanka|Kaja|K|', 'Abi Ghanem|Charly|C|', 'Mhaouty-Kodja|Sakina|S|', 'Ghandour|M Said|MS|', 'Baulieu|Etienne-Emile|EE|', 'Franklin|Robin J M|RJ|', 'Schumacher|Michael|M|', 'Traiffort|Elisabeth|E|']
D000728:Androgens D000818:Animals D001253:Astrocytes D002490:Central Nervous System D049452:Green Fluorescent Proteins D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D008822:Mice, Transgenic D008856:Microscopy, Fluorescence D009186:Myelin Sheath D009457:Neuroglia D009836:Oligodendroglia D011944:Receptors, Androgen D011987:Receptors, Steroid D000074586:Remyelination D012583:Schwann Cells D015398:Signal Transduction D013737:Testis D013739:Testosterone
androgen receptor myelin oligodendrocytes testosterone Schwann cells