Carmen Sato-Bigbee, PhDBiochemistry and molecular biology
Research in our lab is focused on understanding the cellular and molecular mechanisms that control brain development under normal and pathological conditions. A major project investigates the function of the endogenous opioid system and how interference by exogenous opioids may alter those functions. This is a problem of significant importance because of the dramatic raise in opioid abuse and the resulting increase of babies exposed to these drugs during pregnancy. In addition, a high percentage of these infants also require opioids after birth for ameliorating the symptoms of neonatal abstinence syndrome (NAS). Studies using an animal model of perinatal exposure to methadone and buprenorphine, synthetic opioid analogues administered for the treatment of opioid abuse during pregnancy, led us to the discovery of significant effects on the timing of myelination in the developing brain. Furthermore, analysis of myelinated axon calibers and myelin thickness suggested interference with neuron-glia interactions that coordinate axonal outgrowth with myelin formation.Those studies uncover an important role of the endogenous peptide ligands of the mu-opioid (MOR) and Nociceptin (NOR) receptors, Endomorphin-1 and Nociceptin. A complex balance between these peptides controls the extent of oligodendrocyte differentiation and brain myelination preventing precious myelin formation, a situation that could interfere with axonal elongation and neuronal connectivity in the developing brain. In addition, our findings showed that NOR activation at earlier stages of development controls glutamate transporter expression in young astrocytes, suggesting an important role of nociceptin in glutamate homeostasis in the early developing brain. Interestingly, disregulation of the Nociceptin system may also play a role in certain forms of Multiple Sclerosis perhaps precluding remyelination of damaged lesions.
Neurosciences
