Professor of Physiology and of Biochemistry
Dr. Maue received his B.S. in Biology from St. John's University in Minnesota in 1978 and his Ph.D. in Physiology/Pharmacology from the University of California, San Diego in 1985. After postdoctoral training at Brandeis University and New England Medical Center, he joined the faculty of Dartmouth Medical School in 1989 as an Assistant Professor of Physiology and Biochemistry.
We are interested in understanding the mechanisms important for the development and differentiation of neurons in the brain. In particular, we are interested in the means by which a family of growth factors known as neurotrophins (NGF, BDNF, NT-3) exert their influence the growth and electrical activity of neurons, including their regulation of ion channel expression. Our recent efforts have focused on a class of neurons in the brain known as cerebellar Purkinje cells, and our interest in events associated with their development has also included the pathology and abnormal development of these neurons in neurological disorders such as Niemann Pick Type C (NPC) disease. NPC disease is a fatal genetic disorder associated with abnormal cellular cholesterol accumulation, and a hallmark of this disorder is the preferential loss of Purkinje cells. Given the recent appreciation of the importance of cholesterol in the brain and the similarities between NPC disease, Alzheimer’s disease, Huntington’s disease and other neurodegenerative disorders, understanding the effects of NPC disease on Purkinje cells has widespread implications.
In our experiments we have taken advantage of transgenic mice expressing ion channel genes, knockout mice lacking neurotrophin receptors, and novel mouse models of NPC disease that we’ve developed to analyze neurons in primary culture, in brain slices, and in vivo. This has included immunocytochemical and morphometric analyses, Western blotting and biochemical assays, single-cell, real time PCR analyses of gene expression, patch clamp recording of ion channels and electrical activity, virus-mediated expression of fluorescent proteins in vivo and in cultured neurons, and behavioral analyses of cerebellar function. Among future studies include behavioral and histological evaluation of potential treatments for NPC disease, and analysis of genes encoding ion channels, calcium binding proteins, and enyzmes involved in cholesterol metabolism in wild type and mutant Purkinje cells, using single-cell, real time PCR.
Prasad, A., Fischer, W. A., Maue, R. A., and Henderson, L. P. Distribution of the npc1 mRNA in the brain of embryonic and postnatal Niemann Pick Type C (npcnih) mice. J. Neurochem 75(3): 1250-1257 (2000).
Henderson, L.P., Lin, L., Prasad, A., Paul, C. A., Chang, T-Y, and Maue, R. A. Embryonic striatal neurons from Niemann-Pick Type C mice exhibit defects in cholesterol metabolism and neurotrophin responsiveness. J. Biol. Chem. 275(26): 20179-20187 (2000).
Fry, M., Porter, D.M., and Maue, R.A. Adenoviral-mediated expression of functional Na+ channel B1 subunits tagged with a yellow fluorescent protein. J. Neurosci. Res. 74: 794-800 (2003).
Paul, C.A., Boegle, A. K., and Maue, R. A. Before the Loss: Neuronal Dysfunction in Niemann Pick Type C Disease. Biochimica Biophysica et Acta 1685: 63-75 (2004).
Molecular Insights to Ion Channel Biology in Health and Disease (R.A. Maue, Ed.) Elsevier Press Ltd. (2004).
Paul, C.A., Reid, P.C., Boegle, A.K., Karten, B., Zhang, M., Jiang, Z.-G., Franz, D., Lin, L., Chang, T.-Y., Vance, J.E., Blanchette-Mackie, J., and Maue, R. A. Adenovirus expressing an NPC1-GFP fusion gene corrects neuronal and non-neuronal deficits associated with Niemann Pick Type C disease. J. Neurosci . Res. 81(5): 706-719 (2005).
Maue, R.A. Understanding ion channel biology using epitope tags: progress, pitfalls, and promise. J Cellular Physiology 213: 618-625 (2007).
Fry, M, Boegle, A.K., and Maue, R.A. Differentiated pattern of sodium channel expression in dissociated Purkinje neurons maintained in long-term culture. J. Neurochem 101: 737-748 (2007).
[08/20/08]