Tight homeostatic control of the essential trace metals, manganese and iron, is crucial for normal brain physiology. Both manganese and iron are required for neuronal processes including myelination, synaptogenesis, and synaptic plasticity. However, excess or deficiency of either metal are detrimental to neuronal integrity. Trafficking and metabolism of these two metals are closely interlinked but little is known about how their interactions can modulate neuronal function under normal physiological conditions and in ageing. This project aims to elucidate the interplay between manganese and iron within neuronal circuits using zebrafish and neuronal cell models of metal dyshomeostasis.
1 Tuschl K, Meyer E, Valdivia LE, Zhao N, Dadswell C, Abdul-Sada A, Hung CY, Simpson MA, Chong WK, Jacques TS, Woltjer RL, Eaton S, Gregory A, Sanford L, Kara E, Houlden H, Cuno SM, Prokisch H, Valletta L, Tiranti V, Younis R, Maher ER, Spencer J, Straatman-Iwanowska A, Gissen P, Selim LA, Pintos-Morell G, Coroleu-Lletget W, Mohammad SS, Yoganathan S, Dale RC, Thomas M, Rihel J, Bodamer OA, Enns CA, Hayflick SJ, Clayton PT, Mills PB, Kurian MA, Wilson SW. Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood-onset parkinsonism-dystonia. Nat Comms. 2016. 7:11601.
2 Ashraf A, Michaelides C, Walker TA, Ekonomou A, Suessmilch M, Sriskanthanathan A, Abraha S, Parkes A, Parkes HG, Geraki K, So PW (2019). Regional distributions of iron, copper and zinc and their relationships with glia in a normal aging mouse model. Fronts in Aging Neurosci 11: 351.
3 Tuschl K, Taylor CA, Nicolai MM, Bornhorst J, Gubert P, Varão AM, Aschner M, Smith DR, Mukhopadhyay S. Maintaining Translational Relevance in Animal Models of Manganese Neurotoxicity. J Nutr. 2020;150:1360-1369.
4 Tuschl K, White RJ, Valdivia LE, Niklaus S, Bianco IH, Sealy IM, Neuhauss SCF, Houart C, Wilson SW, Busch-Nentwich EM. Loss of slc39a14 causes simultaneous manganese deficiency and hypersensitivity in zebrafish. doi.org/10.1101/2020.01.31.921130.
5 O’Reilly J, Douglas D,Braybrook J, So PW, Vergucht E, Garrevoet J, Vekemans B, Vinczec L, Goenaga-Infante H. A novel calibration strategy for the quantitative imaging of iron in biological tissues by LA-ICP-MS using matrix-matched standards and internal standardisation. J. Anal. At. Spectrom., 2014,29, 1378-1384.