Christopher von Bartheld M.D.
Contact Christopher von Bartheld M.D.
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Manville Health Sciences
Manville Health Sciences
Reno, NV 89557
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We are interested in the function of neurotrophic factors in the developing central nervous system. Neurotrophic factors are messengers in the communication between neurons. They regulate neuronal differentiation and may he instrumental in the formation, stabilization and plasticity of synapses. Targeting of neurotrophic factors to their proper intracellular destination is essential for trophic signalling. Our goal is to understand how trophic factors regulate the development and connectivity of neural circuits. A major focus of our lab is to determine how neurotrophic factors are transported along the axon and how they are released from the axon terminals. We use several model systems, including the developing visual system of chick embryos and rodents as well as the hypoglossal motor nucleus to quantify anterograde and retrograde axonal transport of the neurotrophic factors (Fig. 1).
Fig 1. Transport of radio-iodinated NT-3 from the retina to the isthmo-optic nucleus (ION) and the optic tectum (TeO)) in chick embryos. (von Bartheld, et al., Neuron 12:639-654, 1994 and Nature 379:830-833. 1996)
We manipulate with pharmacological agents the release of these factors from nerve terminals, and we localize them by immunohistochemical and autoradiography techniques at both the light- and electron microscopic level (Fig. 2). By combining molecular, morphological, and pharmacological techniques, we hope to gain insights into the mechanisms and dynamics of trafficking of neurotrophic factors and to better understand how they affect the development, plasticity and possibly regeneration of neuronal connections in the brain.
Fig. 2. Accumulation of NT-3 in terminals of the optic nerve after anterograde axonal transport (von Bartheld et al., Nature 379:830-833,1996).
A second major focus of my lab is the function of neurotrophic factors in the developing oculomotor system, with the long-term goal to strengthen weak eye muscles and their innervation. A third topic of interest is the improvement of methods for counting particles in microscopic tissue sections (part of UNR's COBRE, PI: J. Hume). Workers in the lab include Rafal Butowt, Ph.D. (Res. Assistant Professor: axonal transport of trophic factos and pathogens, electron microscopy and molecular biology), Larisa Baryshnikova (postdoctoral fellow: electron microscopy and quantitative morphology), two graduate students: Scott Croes (neuromuscular development, immunocytochemistry, fluorescence imaging, and electrophysiology/ force measurements), and Chengyuan Feng (Transport of trophic factors, RT-PCR, molecular biology) and one medical student. We are also interested in the evolution of neurotrophic factors and recently organized an international symposium on this topic ("Karger workshop" of the J.B. Johnston Club, a satellite event at the Annual Meeting of the Society for Neuroscience, Nov. 10, Washington DC, 2005), published as a special issue in Brain, Behavior & Evolution, 2006.
- Croes, S.A., Baryshnikova, L.M., Kaluskar, S.S., and C.S. von Bartheld. . Acute and long-term effects of botulinum neurotoxin on the function and structure of developing chick extraocular muscles. Neurobiology of Disease 25:649-664
- Ronald W. Oppenheim, C.S. von Bartheld. . Programmedl Cell Death and Neurotrophic Factors. In: Fundamental Neuroscience (3rd edition). L. Squire (Editor), Elsevier, San Diego (in press)
- von Bartheld, C.S., and Fritzsch, B.. . Comparative analysis of neurotrophin receptors and ligands in vertebrate neurons: tools for evolutionary stability or changes in neural circuits?. Brain, Behavior & Evolution 68: 157-172
- Rind, H.B., Butowt, R., C.S. von Bartheld. . Synaptic targeting of retrogradely transported trophic factors in motoneurons: comparison of glial cell line-derived neurotrophic factor, brain-derived neurotrophic factor and cardiotrophin-1 with tetanus toxin. Journal of Neuroscience 25: 539-549
- von Bartheld, C.S.. . Axonal transport and neuronal transcytosis of trophic factors, tracers and pathogens. Journal of Neurobiology 58:294-314
- Chen, J., von Bartheld, C.S.. . Role of exogenous and endogenous trophic factors in the regulation of extraocular muscle strength during development. Investigative Ophthalmology & Visual Science 45:3538-3545
- Butowt, R., C.S. von Bartheld.. . Connecting the dots: trafficking of neurotrophins, lectins and diverse pathogens by binding to the neurotrophin receptor p75NTR. European Journal of Neuroscience 17:673-680
- von Bartheld, C.S.. . Counting particles in tissue sections: choices of methods and importance of calibration to minimize bias. Histology & Histopathology 17:639-648
- Wang, X.X., R. Butowt, M.R. Vasko, C.S. von Bartheld. . Mechanisms of the release of anterogradely transported neurotrophin-3 from axon terminals. Journal of Neuroscience 22:931-945
- von Bartheld, C.S., X.X. Wang, R. Butowt. . Anterograde axonal transport, transcytosis and recycling of neurotrophic factors: the concept of trophic currencies in neural networks. Molecular Neurobiology 24:1-28
- von Bartheld, C.S.. . Comparison of 2-D and 3-D counting: the need for calibration and common sense. Trends in Neurosciences 24:504-506
- von Bartheld, C.S.. . Tracing with radiolabeled neurotrophins. Methods in Molecular Biology 169:195-216
- von Bartheld, C.S., M.R. Byers, R. Williams, M. Bothwell. . Anterograde transport of neurotrophins and axodendritic transfer in the developing visual system. Nature 379:830-833
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