BBS Faculty Member - Paul Rosenberg

Paul Rosenberg

Department of Neurology

Boston Children's Hospital
Center for Life Sciences Building, Room 13073
300 Longwood Avenue
Boston, MA 02115
Tel: 617-919-2634
Fax: 617-919-2380
Visit my lab page here.

Glutamate transport
Neurotransmitter transporters, like ion channels, play essential roles at synapses in the central nervous system. Glutamate transport is important in the physiology of excitatory synapses and protects neurons and oligodendrocytes (OLs) against excitotoxicity. We are studying the regulation of expression of glutamate transporters and the mechanisms linking their function to neuronal activity. This work has involved cloning of novel forms of glutamate transporters, identifying and characterizing protein interactors, and investigating mechanisms of signal transduction that regulate transporter activity. Two major accomplishments of the past 5 years has been the demonstration that GLT1, the major glutamate transporter of the brain, thought to be exclusively localized in astrocytes, is expressed in excitatory terminals of the hippocampus, and that the synaptic protein PICK1 is a biologically significant interactor with GLT1 and other glutamate transporters. Our hypothesis is that GLT1 is the major glutamate reuptake system in excitatory terminals in the cerebrum. We are now interested in the implications of this discovery for our understanding of the normal function of excitatory synapses and of their abnormal function leading to excitoxicity in ischemic injury and Huntington’s disease.

Mechanisms of oligodendrocyte injury
We study periventricular leukomalacia (PVL), the principal pathological lesion underlying cerebral palsy in premature infants. The primary cell-type injured in this lesion is the OL. For this reason, it is important to understand the mechanisms of death that kill OLs that might be activated in PVL. We have discovered that developing OLs are more vulnerable than mature OLs to both oxidative and excitotoxic injury. We are characterizing the mechanisms of cell death, the basis for the developmental regulation of the vulnerability to injury, as well as possible approaches for therapeutic intervention.

Nitric oxide (NO) and the regulation of behavioral state
We hypothesize that elevation of NO, synthesized by inducible nitric oxide synthase (iNOS) in the BF during prolonged wakefulness, is a specific pathway for producing non-REM recovery sleep. We are now attempting to localize the cells in which iNOS is expressed in response to sleep deprivation by a combination of techniques. Once that is accomplished, we will want to know what activates iNOS in those cells, what cells are the target of the nitric oxide produced by those cells, and what the nitric oxide does in those cells. In this work the aim is to establish a molecular understanding of the regulation of behavioral state.

Last Update: 8/22/2013


For a complete listing of publications click here.



Chen, W., Mahadomrongkul, V., Berger, U.V., Bassan, M., DeSilva, T., Tanaka, K., Irwin, N., Aoki, C., Rosenberg, P.A. The glutamate transporter GLT1a is expressed in excitatory axon terminals of mature hippocampal neurons. Journal of Neuroscience. 2004;24:1136-1148.

Kalinchuk, A.V. Lu, Y. Stenberg, D. Rosenberg, P.A. Porkka-Heiskanen, T. Inducible and neuronal nitric oxide have complementary roles in homeostatic sleep regulation. European Journal of Neuroscience. 2006;24(5):1443-1456.

Bassan, M., Liu, H., Madsen, K.L., Armsen, W., Zhou, J., Desilva, T., Chen, W., Paradise, A., Brasch, M.A., Staudinger, J., Gether, U., Irwin, N., Rosenberg, P.A. Interaction between the glutamate transporter GLT1b and the synaptic PDZ domain protein PICK1. European Journal of Neuroscience. 2008;27(1):66-82.

Li, J., Ramenaden, E.R., Peng, J., Koito, H., Volpe, J.J., Rosenberg, P.A. Tumor necrosis factor alpha mediates lipopolysaccharide-induced microglial toxicity to developing oligodendrocytes when astrocytes are present. Journal of Neuroscience. 2008;28(20): 5321-5330.

© 2013 by the President and Fellows of Harvard College