The Molecular Neuroscience research group in the Department of Biological and Medical Sciences has a long-term interest in the structural and functional relationships of ligand-gated ion channels, with particular emphasis on nicotinic acetylcholine receptors (nAChR). These receptors have been implicated in a wide range of diseases of the brain, including Alzheimer’s and Parkinson’s diseases, Tourette syndrome, schizophremia, autism, drug addiction and attention deficit disorders, and are therefore high-quality targets for drug therapy.

The overall goal of the research is to isolate and characterise plant- and animal-derived compounds for probing the structure and function of nAChR and providing new leads for the development of selective therapeutic substances.

The techniques of molecular biology, in vitro functional studies using primary or clonal cell cultures, radioligand-binding assays and electrophysiological recordings are combined to provide a multidisciplinary approach to the topic.

Franklin, M., Bermudez, I., Mucha, S., Singewald, N., Gaburro, S. & Murck, H. 2010. Time defining effects of tryptophan depletion on hormone secretion and brain 5-HT2 binding in the rat. European Neuropsychopharmacology, 20, S357-S357. Iturriaga-Vasquez, P., Carbone, A., Garcia-Beltran, O., Livingstone, P. D., Biggin, P. C., Cassels, B. K., Wonnacott, S., Zapata-Torres, G. & Bermudez, I. 2010. Molecular Determinants for Competitive Inhibition of alpha 4 beta 2 Nicotinic Acetylcholine Receptors. Molecular Pharmacology, 78, 366-375 Carbone, A. L., Moroni, M., Groot-Kormelink, P. J. & Bermudez, I. 2009. Pentameric concatenated (alpha 4)(2)(beta 2)(3) and (alpha 4)(3)(beta 2)(2) nicotinic acetylcholine receptors: subunit arrangement determines functional expression. British Journal of Pharmacology, 156, 970-981. Franklin, M., Bermudez, I., Aveyard, P. N., Parsons, A. & Ingram, J. 2010. Treatment effects of St John's Wort and chromium (3+) in a randomised double-blind placebo controlled trial on early waking salivary cortisol in quitting smokers is TINS related to relapse'? Journal of Psychopharmacology, 24, A31-A31. Singewald, N., Sartori, S. B., Gaburro, S., Schmuckermair, C., Hetzenauer, A., Rjabokon, A., Franklin, M., Bermudez, I., Murck, H., Shin, J. H., Lin, L., Lubec, G. & Whittle, N. 2010. Rodent magnesium-deficiency models for depression and their relationship to NMDA receptor/Nitric Oxide pathways. European Neuropsychopharmacology, 20, S366-S366. Parsons, A., Ingram, J., Inglis, J., Aveyard, P., Johnstone, E., Brown, K., Franklin, M. & Bermudez, I. 2009. A proof of concept randomised placebo controlled factorial trial to examine the efficacy of St John's wort for smoking cessation and chromium to prevent weight gain on smoking cessation. Drug and Alcohol Dependence, 102, 116-122. Moroni, M., Vijayan, R., Carbone, A., Zwart, R., Biggin, P.C. and Bermudez, I. (2008). Non-agonist-binding subunit interfaces confer distinct functional signatures to the alternate stoichiometries of the alpha 4 beta 2 nicotinic receptor: An alpha 4-alpha 4 interface is required for Zn2+ potentiation. Journal of Neuroscience 28, 6884-6894. Zwart, R., Carbone, A.L., Moroni, M., Bermudez, I., Mogg, A.J., Folly, E.A., Broad, L.M., Williams, A.C., Zhang, D., Ding, C., et al. (2008). Sazetidine-A is a potent and selective agonist at native and recombinant alpha 4 beta 2 nicotinic acetylcholine receptors. Molecular Pharmacology 73, 1838-1843. Carbone, A.L., Moretti, M., Zwart, R., Gotti, C. and Bermudez, I. (2007). Functional and radioligand binding properties of alternate stoichiometries of human alpha 4 beta 2 nAChRs. Biochemical Pharmacology 74, SMA11-SMA12. Iturriaga-Vasquez, P., Perez, E.G., Slater, E.Y., Bermudez, I. and Cassels, B.K. (2007). Aporphine metho salts as neuronal nicotinic acetylcholine receptor blockers. Bioorganic & Medicinal Chemistry 15, 3368-3372. Moroni, M., Vijayan, R., Biggin, P., Carbone, A.L. and Bermudez, I. (2007). Identification of molecular determinants that mediate zinc effects on alternate stoichiometries of the human alpha 4 beta 2 nicotinic acetylcholine receptors. Biochemical Pharmacology 74, SMA11-SMA11.