Scientific Focus
Neurons in the brain remodel their structure under conditions of learning and memory as well as under conditions of brain disease (e.g., brain injury, Alzheimer´s disease; Parkinson´s disease). The lab is devoted to understanding the dynamics and the underlying molecular mechanisms of these reorganizational processes and searches for novel therapeutic strategies aimed at (i) preventing neuronal loss ("neuroprotection") and (ii) the identification of naturally occurring repair mechanisms that can be exploited to promote functional regeneration ("neuroregeneration"). To achieve this mission, cellular approaches and disease models are employed to study the cellular fundamentals and these data are correlated with data from human brains of patients suffering from neurodegenerative diseases.
The main current projects are focusing on:
1. Structural plasticity of neurons under conditions of synaptic stimulation.
2. Structural reorganization of neurons following denervation.
3. Structural alterations of neurons in the context of disease models (Alzheimer´s disease, Parkinson´s disease)
4. Structural pathology of neurons during human neurodegenerative diseases (Alzheimer´s disease, Parkinson´s disease, polyglutamine diseases. Clinicopathological correlation studies and risk factor analysis.
Methods
Methods (lab):
- morphological techniques: Immunohistochemistry, electron microscopy, Neurolucida-reconstructions, stereology, in situ hybridization, FISH, unconventionally thick Nissl-stained sections for neuroanatomical analysis of human brains (Braak-technique)
- cell biological techniques: Organotypic slice cultures, dissociated neuronal cultures, adenoviral transfection techniques, laser microdissection in combination with real-time RT-PCR.
- electrophysiological techniques: in vivo LTP, extracellular recording techniques.
- imaging techniques: time-lapse imaging (confocal microscopy), multiphoton microscopy, Ca2+-imaging.
- model systems: Entorhinal denervation model (in vivo; in vitro); nigro-striatal model (in vitro), disease models (Alzheimer´s disease; Parkinson´s disease).
Selected Publications
1. Haas CA, Rauch U, Thon N, Merten T, Deller T (1999) Entorhinal cortex lesion in adult rats induce the expression of the neuronal chondroitin sulfate proteoglycan neurocan in reactive astrocytes. J Neurosci 19: 9953-9963.
2. Pfeifer M, Boncistiano S, Bondolfi L, Stalder A, Deller T, Staufenbiel M, Mathews P, Jucker M (2002) Cerebral hemorrhage following anti-Aß Immunotherapy. Science 298: 1379.
3. Deller T, Korte M, Chabanis S, Drakew A, Schwegler H, Stefani GG, Zuniga A, Schwarz K, Bonhoeffer T, Zeller R, Frotscher M, Mundel P (2003) Synaptopodin-deficient mice lack a spine apparatus and show deficits in synaptic plasticity. Proc Natl Acad Sci USA 100: 10494-10499.
4. Burbach GJ, Hellweg R, Haas CA, Del Turco D, Deicke U, Abramowski D, Jucker M, Staufenbiel M, Deller T (2004) Induction of brain-derived neurotrophic factor (BDNF) in plaque-associated glial cells of aged APP23 transgenic mice. J Neurosci 24: 2421-2430.
5. Tegeder I, Del Turco D, Schmidtko A, Sausbier M, Feil R, Hofmann F, Deller T, Ruth P, Geisslinger G (2004) Reduced inflammatory hyperalgesia with preservation of acute thermal nociception in mice lacking cGMP-dependent protein kinase-I. Proc Natl Acad Sci USA 101: 3253-3257.
6. Valente EM, Abou-Sleiman PM, Caputo V, Muqit MMK, Harvey K, Gispert S, Ali Z, Del Turco D, Bentivoglio AR, Healy DG, Albanese A, Nussbaum R, González-Maldonado R, Deller T, Salvi S, Cortelli P, Gilks WP, Latchman DS, Harvey RJ, Dallapiccola B, Auburger G, Wood NW (2004) Hereditary early-onset Parkinson’s disease caused by mutations in PINK1. Science 304: 1158-1160.
7. Jen JC, Chan WM, Bosley TM, Wan J, Carr JR, Rüb U, Salamon G, Kudo L, Ou J, Salih MAM, Kansu T, Dhalaan H, Al Zayed Z, Dretakis EK, Plaitakis A, Gottlob I, Pieh C, Traboulsi EI, MacDonald D, Stigsby B, Kim G, Andrew C, Yamada K, Demer JL, Kornblum HI, Hageman N, Alger J, Shattuck D, Geschwind DH, Deller T, Sicotte NL, Nelson SF, Baloh RW, Engle EC (2004) Mutations in a human Robo gene disrupt hindbrain axon pathway crossing and morphogenesis. Science 304: 1509-1513.
8. Stanke M, Duong CV, Pape M, Geissen M, Burbach GJ, Deller T, Gascan H, Parlato R, Schütz G, Rohrer H (2006) Target-dependent specification of the neurotransmitter phenotype: Cholinergic differentiation of sympathetic neurons is mediated in vivo by gp130 signaling. Development 133: 141-50.
9. Schulte U, Thumfart J-O, Klöcker N, Sailer C, Bildl W Biniossek M, Dehn D, Deller T, Eble S, Abbass K, Wangler T, Knaus H-G, Fakler B (2006) The epilepsy-linked Lgi1 protein assembles into presynaptic Kv1 channels and inhibits inactivation by Kvß1. Neuron 49: 697-706.
10. Custer SK, Garden GA, Gill N, Rüb U, Libby RT, Schultz C, Guyenet SJ, Deller T, Westrum LE, Sopher BL, La Spada AR (2006) Bergmann glia expression of polyglutamine-expanded ataxin-7 produces Purkinje cell degeneration in SCA7 by impairing glial glutamate transport. Nature Neurosci 9: 1302-1311.
11. Bas Orth C, Schultz C, Müller CM, Frotscher M, Deller T (2007) Loss of the cisternal organelle in the axon initial segment of cortical neurons in synaptopodin-deficient mice. J Comp Neurol 504:541-549.
12. Vuksic M, Del Turco D, Bas Orth C, Burbach GJ, Feng G, Müller CM, Schwarzacher SW, Deller T (2008) 3D-reconstruction and functional properties of GFP-positive and GFP-negative granule cells in the fascia dentata of the Thy1-GFP mouse. Hippocampus, in press.
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