Department of Neurology
Charles Abrams, M.D., Ph.D.
Associate Professor of Neurology
Director, Neuromuscular Division
SUNY Downstate Medical Center, Brooklyn, NY
The over-arching theme of the work in my laboratory is the roles of connexins in the function of
central and peripheral nervous system glia. The connexins comprise a large family of
homologous integral membrane proteins that form (GJ) channels; to date more than 20 connexins
have been identified. Connexins form gap junctions, which provide a low resistance channels for
the diffusion of small molecules and ions between coupled cells; however, recent data suggest
that connexins may have roles in regulation of cell growth and resistance to both apoptotic and
necrotic cell death that are independent of formation of functional gap junction channels. Our
laboratory is focused in several specific areas.
1) Charcot-Marie-Tooth disease is a group of inherited disorders that predominantly or
exclusively affect the peripheral nervous system. CMTX, the X-linked form of Charcot-Marie-Tooth disease, is associated with mutations in connexin 32 (Cx32), a gap junction protein
expressed in Schwann cells (SCs). Over the last few years my laboratory has focused on
elucidating the mechanisms by which CMTX mutations lead to peripheral neuropathy.
2) In developing and regenerating peripheral nerves, promyelinating SCs express Cx32 mRNA
and protein in conjunction with the expression of myelin specific genes. We are currently
investigating the role of Cx32 in control of SC proliferation.
3) Mutations in human CX47 cause either a mild disorder, hereditary spastic paraparesis (HSP)
or a more severe disorder, Pelizaeus- Merzbacher Like Disease (PMLD). Evaluation of Cx47
mutations that cause PMLD show that these mutations cause complete loss of function including
disruption of O/A coupling, while the mutation causing HSP appears to lead to partial loss of
function. We are currently using DNA microarray studies to examine the effects of expression of
WT vs. mutant forms of Cx47 on expression of other genes in virally infected oligodendrocytes.
4) Because Cx32 and Cx47 seem to be required for myelin stability, we are currently examining
the hypothesis that mice lacking either of these connexins may be more susceptible to
demyelination. Preliminary experiments suggest that Cx47 knockout mice are more susceptible
to Experimental Allergic Encephalitis than are wild-type mice.
- Huang, Y. Grinspan, J. B. Abrams, C.K., Scherer S.S. (2007) Pannexin1 is expressed by neurons
and glia but does not form functional gap junctions. Glia 55:46-56.
- Orthmann, J.M., Abrams, C.K.,.,Enriquez, A.E., and Scherer, S.S. (2007) Loss-of-function
GJA12/Connexin47 mutations cause Pelizaeus-Merzbacher-like disease.. Mol Cell Neurosci.
- Orthmann-Murphy J.L., Freidin M., Fischer E., Scherer S.S., Abrams C.K. (2007) Two distinct
heterotypic channels mediate gap junction coupling between astrocyte and oligodendrocyte
connexins. J Neurosci. 27:13949-57.
- Ahn M., Lee J., Gustafsson A., Enriquez A, Lancaster .L, Sul J.Y., Haydon P., Paul D.L., Huang
Y., Abrams C.K., and Scherer S.S. (2008) Connexin29 and Connexin32, two connexins
expressed by myelinating glia, do not interact and are functionally distinct. J. Neurosci. Res.
- Sargiannidou I., Ahn M., Enriquez A.D., Peinado A., Reynolds R., Abrams C., Scherer
S.S.,Kleopa K.A. (2008) Human oligodendrocytes express Cx31.3: function and interactions
with Cx32 mutants. Neurobiol Dis. 30:221-33.
- Orthmann-Murphy J., Abrams C.K., Scherer S.S. (2008) Gap junctions couple astrocytes and
oligodendrocytes. J. Mol Neurosci. 35:101-16.
- Orthmann-Murphy JL, Salsano E, Abrams C.K., Bizzi A, Uziel G, Freidin MM, Lamantea E,
Zeviani M, Scherer SS, Pareyson D (2009) Hereditary spastic paraplegia is a novel phenotype for
GJA12/GJC2 mutations. Brain. 132:436-438.
- Freidin M., Asche S., Bargiello T.A., Bennett M.V.L., and Abrams C.K. (2009) Connexin 32
increases the proliferative response of Schwann cells to neuregulin-1 (Nrg1) Proc. Natl. Acad.
- Abrams, C. K., Rash, J.E. (2009) “Connexins In The Nervous System”, In Connexins: A Guide.
(Harris, A and Locke, D., editors). PP 323-357. Humana Press, Totowa N.J.
- Abrams, C. K., Orthmann, Murphy, J. L., Fischer, E., Freidin, M. M., and Scherer S. S. “Connexins In Myelinating Glia”: In Proceedings of the 9th European Meeting on Glial Cells in
Health and Disease (September 8-12, 2009, Paris, France).
- Sameh K. Wasseff, Charles K. Abrams, and Steven S. Scherer. (2010) A dominant Cx43 mutant
does not have dominant effects on gap junction coupling. (Submitted)