Paul A. Rosenberg, MD/PhD
Associate Professor of Neurology
Harvard Medical School/Children's Hospital
Department of Neurology (Neuroscience)

MRRC Project(s)

R01 NS41883
Regulation of EAAT2 in the Developing Human Brain

R01 NS40753
Glutamate Transport and Transporters in Rat Forebrain Neurons

P01 NS38475
Periventricular Leukomalacia in the Premature Infant -
PI, Project 3: Mechanisms of Free Radical Mediated Injury to Developing Oligodendrocytes

SCOR HL 60292
Harvard Center on the Neurobiology of Sleep and Sleep Apnea

Glutamate Transport and Transporters

A central focus in my laboratory is the role of glutamate transport in the physiology and pathophysiology of excitatory synapses and in excitotoxic neuronal death. Although glutamate transport has been assumed to be largely a function of astrocytes, evidence from a variety of approaches suggests that neuronal glutamate uptake mechanisms are important as well, both for the physiology of excitatory transmission as well as for the pathophysiology of excitotoxicity. We are identifying and characterizing the transporters that are present in forebrain neurons, how their expression changes through rodent and human development, how they are targeted to synapses, and how their activity is regulated.

Mechanisms of Oligodendrocyte Injury

Periventricular leukomalacia (PVL) is the principal pathological lesion underlying cerebral palsy in premature infants, and a key cell-type injured in this lesion is the oligodendrocyte. For this reason, it is important to understand the mechanisms of death present in oligodendrocytes that might be activated in PVL. In collaboration with Dr. Joseph Volpe we have developed methods for growing oligodendrocytes in relatively pure culture based on immunopanning and serum-free defined medium and have used these cultures to investigate basic mechanisms underlying oligodendrocyte injury and death.

Molecular Regulation of Adenosine Inhibition Relevant to Control of Behavioral State

Adenosine is an inhibitory neuromodulator that has been postulated to be involved in behavioral state control in several regions of the brain, including the cerebral cortex, thalamus, basal forebrain, and lateral dorsal tegmental/pedunculopontine tegmental nucleus (LDT/PPT). Adenosine inhibits firing of cholinergic cells of the LDT/PPT, and this action may be related to its effects on arousal. Little is known about the molecular regulation of adenosine levels in the extracellular space in any brain region. We are actively trying to understand these mechanisms of adenosine regulation relevant to behavioral state control. Most recently we have focused on the potential role of nitric oxide in regulating behavioral state via modulation of extracellular adenosine.