Research Interests:Our laboratory studies how brain cells integrate and coordinate the various membrane transport activities controlling the fluxes and compartmentation of amino acid neurotransmitters and their metabolic precursors. The goal is to understand how these fluxes are normally regulated and how their perturbation may underlie disease. A major focus of our research has been the role of astrocytes in the glutamate-glutamine cycle. Glutamate released at synapses is taken up by astrocytes which are uniquely equipped to detoxify both ammonia and glutamate by converting them to glutamine. Glutamine is then exported by astrocytes to serve as a precursor for neurotransmitter synthesis by neurons. Disturbances of the glutamate-glutamine cycle are implicated in a variety of neurodegenerative disorders associated with aging and exposure to environmental neurotoxicants. Our laboratory exploits the experimental access afforded by cell culture of specific brain cell types. We characterize membrane transport and permeation in neurons, neuroglia and cerebrovascular endothelial cells by means of radiolabelled tracers, spectrofluorometry and HPLC. Intracellular fluorescent probes are used to explore regulatory mechanisms. Collaborative arrangements extend these studies to the properties and distribution of identified transporter molecules. By examining the effect of intercellular and intracellular signals on transport and permeation, we provide a basis for understanding how the microenvironment of neurons is controlled.
Lab Techniques and Equipment:
• Central nervous system cell culture
• Transport of radioactive tracers
• Amino acid HPLC
• Ratio spectrofluorometry using intracellular fluorescent probes
• Molecular and immunocytochemical techniques in collaboration with other laboratories
PhD in Pharmacology, Leeds University Medical School, U.K., training with Dennis Mackay, studying the kinetics of drug transport and distribution in tissues; postdoctoral training with John Wolstencroft and Philip Bradley, M.R.C. Experimental Neuropharmacology Unit, University of Birmingham Medical School, U.K., studying monoamine pharmacology in the brain stem; postdoctoral training with Robert Werman, Department of Pharmacology, Hebrew University- Hadassah Medical School, Jerusalem, training in quantitative analysis of neurotransmitter-receptor interactions.
Broer, A., Brookes, N., Ganapathy, V., Dimmer, K.S., Wagner, C.A., Lang, F., and Broer, S. (1999) The astroglial ASCT2 amino acid transporter as a mediator of glutamine efflux. Journal of Neurochemistry 73: 2184-2194.
Brookes, N. (2000) Functional integration of the transport of ammonium, glutamate and glutamine in astrocytes. Neurochemistry International 37: 121- 129.
Broer, S. and Brookes, N. (2001) Review - Glutamine transfer between astrocytes and neurons. Journal of Neurochemistry 17: 705-719.
Brookes, N. (2002) Ammonium ion transport in astrocytes: functional implications, in Neuroglia in the Aging Brain (de Vellis, J., ed.) Humana Press, Totowa, NJ, pp. 275-288.
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