Carmen Sato-Bigbee, Ph.D.Associate Professor of Biochemistry & Molecular Biology
PO Box 980614
Richmond, VA 23298-0614
- B.S., 1979, Buenos Aires University, Argentina
- Ph.D., 1985, Buenos Aires University
- Dept of Neurology, Yale Univ. School of Medicine, 1985-1988
- Dept of Biochemistry, VCU, 1988-1995
The studies in our laboratory are focused on understanding the molecular mechanisms that control the differentiation of oligodendrocytes and the formation of the myelin membrane in the central nervous system (CNS), both under normal and pathological conditions.
The myelin membrane is an intricate structure that wraps around the neuronal axons insulating them and allowing the rapid “saltatory” conduction of nerve impulses. However, recent studies have indicated that in addition to this classical function, the myelin membrane and the myelin-making oligodendrocytes are also important regulators of plasticity and remodeling in the developing CNS. Supporting these roles, there is evidence correlating increased myelin formation with experience and enhanced function of the human infant and adolescent brain. Furthermore, myelin alterations have recently been associated to a variety of neurological problems, including schizophrenia, autism, and nervous system dysfunction in normal and pathological aging of the brain.
A- cultured oligodendrocytes
B- Electron microscopy of an oligodendrocyte myelinating multiple axons in the developing rat brain
We have recently found that perinatal exposure to opioids that are used for the treatment of pregnant opioid addicts, alters myelination in the developing rat brain. Thus, one of our the projects is investigating the roles of the endogenous opioid system in regulating myelin formation, and understanding the mechanisms by which opioid abuse and related treatments during pregnancy and postnatal detoxification may interfere with this important process in the developing brain. This information should be crucial to the design of safer treatments for both pain control and drug addiction during pregnancy, minimizing deleterious effects in the maturing brain.
Buprenorphine, an opioid analogue used in clinical trials for the treatment of opioid addicts, affects oligodendrocytes by activation of mu-opioid- and nociceptin receptors with opposing effects on cell differentiation.
A parallel project is investigating the role of these molecular mechanisms in the pathogenesis of multiple sclerosis, a disease in which myelin loss is the leading cause of neurological disability in young adults. We expect that targeting of these mechanisms could result in novel pharmacological treatments to stimulate remyelination in the damaged brain and spinal cord.
- Eschenroeder AC, Vestal-Laborde AA, Sanchez ES, Robinson SE, Sato-Bigbee C (2012) Oligodendrocyte responses to buprenorphine
uncover novel and opposing roles of the μ-opioid and nociceptin/orphanin FQ receptors in cell development: Implications for drug
addiction treatment during pregnancy. Glia 60(1), 125-136. Epub Oct 14, 2011.
- Coelho RP, Yuelling LM, Fuss B, Sato-Bigbee C (2009) Neurotrophin-3 targets
the translational initiation machinery in oligodendrocytes. Glia 57(16):1754-64.
- Pomicter AD, Shroff SM, Fuss B, Sato-Bigbee C Brophy PJ, Rasband MN,
Bhat M, Dupree JL (2010) Novel forms of neurofascin 155 in the CNS: alterations
in paranodal disruption models and multiple sclerosis. Brain. 133:389-405.
- Coelho RP, Saini HS, Sato-Bigbee C (2009) Sphingosine-1-phosphate and oligodendrocytes:
From cell development to the treatment of multiple sclerosis. Prostaglandins and Other
Lipid Mediators. 91(3-4), 139-144.
- Sanchez ES, Bigbee JW, Fobbs W, Robinson SE, Sato-Bigbee C (2008) Opioid addiction and Pregnancy:
Perinatal exposure to buprenorphine affects myelination in the developing brain. Glia 56, 1017-1027.
- Coelho RP, Payne SG, Bittman R, Spiegel S, Sato-Bigbee C (2007) The immunomodulator FTY720 has a direct
cytoprotective effect in oligodendrocyte progenitors. J. Pharmacol. Exp. Ther. 323, 626-635.