A Novel Fluorescent Probe That Is Brain Permeable and Selectively Binds to Myelin

Author:

Wu Chunying1,Tian Donghua2,Feng Yue2,Polak Paul3,Wei Jingjun1,Sharp Adam3,Stankoff Bruno4,Lubetzki Catherine4,Zalc Bernard4,Mufson Elliott J.5,Gould Robert M.6,Feinstein Douglas L.3,Wang Yanming1

Affiliation:

1. Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, Illinois

2. Department of Pharmacology, Emory University, Atlanta, Georgia

3. Department of Anethesiology, University of Illinois at Chicago, Chicago, Illinois

4. Biologie des Interactions Neurones/Glie, Hopital de la Salpetriere, Paris, France

5. Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois

6. Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, Illinois

Abstract

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.

Publisher

SAGE Publications

Subject

Histology,Anatomy

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