A novel fluorescent probe that is brain permeable and selectively binds to myelin.
Myelin is a multilayered glial cell membrane that forms segmented sheaths around large-caliber axons of both the central nervous system (CNS) and peripheral nervous system (PNS). Myelin covering insures rapid and efficient transmission of nerve impulses. Direct visual assessment of local changes of myelin content in vivo could greatly facilitate diagnosis and therapeutic treatments of myelin-related diseases. Current histologic probes for the visualization of myelin are based on antibodies or charged histochemical reagents that do not enter the brain. We have developed a series of chemical compounds including (E,E)-1,4-bis(4'-aminostyryl)-2-dimethoxy-benzene termed BDB and the subject of this report, which readily penetrates the blood-brain barrier and selectively binds to the myelin sheath in brain. BDB selectively stains intact myelinated regions in wild-type mouse brain, which allows for delineation of cuprizone-induced demyelinating lesions in mouse brain. BDB can be injected IV into the brain and selectively detect demyelinating lesions in cuprizone-treated mice in situ. These studies justified further investigation of BDB as a potential myelin-imaging probe to monitor myelin pathology in vivo.
Wu
Chunying
C
Department of Medical Chemistry and Pharmacognosy, University of Illinois at Chicago, USA, and Biologie des Interactions Neurones/Glie, Hopital de la Salpetriere, Paris, France.
Tian
Donghua
D
Feng
Yue
Y
Polak
Paul
P
Wei
Jingjun
J
Sharp
Adam
A
Stankoff
Bruno
B
Lubetzki
Catherine
C
Zalc
Bernard
B
Mufson
Elliott J
EJ
Gould
Robert M
RM
Feinstein
Douglas L
DL
Wang
Yanming
Y
D000814:Aniline Compounds / Q000493:pharmacokinetics; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D003471:Cuprizone; D003711:Demyelinating Diseases / Q000378:metabolism; D005260:Female; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009186:Myelin Sheath / Q000378:metabolism*; D010539:Permeability; D013267:Stilbenes / Q000493:pharmacokinetics
C513504:1,4-bis(4'-aminostyryl)-2-dimethoxybenzene; D000814:Aniline Compounds; D005456:Fluorescent Dyes; D013267:Stilbenes; D003471:Cuprizone