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CNC Research
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Neurogenesis and Neural Stem Cells
January 29 - February 2
Inês Araújo e Cristina Rego
Invited lecturers:

- Allison Ebert, PhD, Waisman Center, University of Wisconsin, Madison, USA
Email: ebert@waisman.wisc.edu
Web: http://www.waisman.wisc.edu/scrp/

- Mónica Sousa, PhD, Instituto Biologia Molecular e Celular (IBMC), Molecular Neurobiology Group, Porto, Portugal
Email: msousa@ibmc.up.pt

- Jia-Yi Li, MD, PhD Neuronal Survival Unit, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, Lund, Sweden
E-mail: jia-yi.li@med.lu.se
Web: http://www.nesu.mphy.lu.se/

João Bettencourt Relvas, MD, PhD ETH Zurich, Institute of Cell Biology, Zurich, Switzerland
E-mail: joao.relvas@cell.biol.ethz.ch
Web: http://www.neuroscience.unizh.ch/e/groups/relvas00.htm

Course objectives
This course will focus on the latest research in the field of neural stem cells, particular stem cells that give rise to the several types of cells in the nervous system, starting in the embryonic development and throughtout the entire adult life. Neural stem cell research has grown exponentially in the recent years, given the interest in better understanding the role of these cells and their potential for brain repair in neurodegenerative disorders. Whether by transplantation or by stimulation of endogenous stem cells, the possibilities are several for improving the clinical outcome in a variety of disorders. Thus, this course is intended to promote the understanding of the features, plasticity, and roles of stem cells in the brain, and possible applications of neural stem cells in clinical use. Neural stem cells are also the research target of several groups at the CNC.
Course Schedule

Monday (Jan 29)
10:00 -10:30 Introductory Remarks
10:30 -11:30 Human neural progenitor cells: how we get them and what we can
do with them - Allison Ebert
14:00 -15:00 Integrin signaling in the regulation of neural stem and progenitor
cell differentiation - João Relvas
15:30-16:30 Isolation, growth, and manipulation of human neural progenitor cells Allison Ebert

Tuesday (Jan 30)

9:00-10:00 Neural progenitor differentiation: oligodendrocytes and myelination - João Relvas
10:30-11:30 Clinical use of embryonic versus adult stem cells: limitations and applications - Mónica Sousa
14:00-15:00 Neural stem and progenitor cells in demyelinating diseases - João Relvas

10:00-11:00 Towards neural stem/progenitor cell therapy in multiple sclerosis and leukodystrophies - Mónica Sousa
11:30-12:30 Ex vivo gene therapy using human neural progenitor cells 
 - Allison Ebert
14:30-15:30 The neural stem cell-brain tumor link: work in progress- Mónica Sousa

9:00-10:00 From bird songs to adult mammalian neurogenesis - Mónica Sousa
10:30-11:30 Modulation of neurogenesis: physiological and pathophysiological aspects
Jia-Yi Li
14:00-15:00 Disturbances of neurogenesis in neurodegenerative diseases- Jia-Yi Li
15:30-16:30 Human neural progenitor cells: A cell source for transplantation in neurodegenerative diseases - Allison Ebert


9:00-12:00 Reading assignments (15 min presentations):

Students presenting:
Pdf 1 - Ana Caldeira Burgeiro, Ana Catarina Oliveira and Daniel Farinha Nunes
Pdf 2 - Alexandra Isabel Rosa, Mirka Kapcalova and Gil Pereira Costa
Pdf 3 - Ana Raquel Soares, David Arboleda and Joana Margarida Gaspar
Pdf 4 - Ana Cristina Silva, Daniela Arduíno and Cecilia Gonzalez-Campo
Pdf 5 - João Filipe Martins and Luís Santos Bimbo
Pdf 6 - Ana Filipa Domingues and Rui Mamede Cruz
Pdf 7 – Joana Filipa Neves, Bruno Carreira and Pedro Manuel Branco
Pdf 8 – Marina Lurdes B. Brito, Ana Raquel Esteves and Vera Sofia Ribeiro
Pdf 9 - Sara Maurício Sousa, Rui Costa and Sofia Soares Grade

16:00-17:00 Seminar: Application of neural stem cells for brain repair in neurodegenerative disorders – the case of Parkinson’s and Huntington’s diseases - Jia-Yi Li

Reading assignments:

Pdf 1

Sousa KM, Mira H, Hall AC, Jansson-Sjostrand L, Kusakabe M, Arenas E.
Microarray analyses support a role for Nurr1 in resistance to oxidative stress and neuronal differentiation in neural stem cells. Stem Cells. 2006 Oct 12

Pdf 2
McKenzie IA, Biernaskie J, Toma JG, Midha R, Miller FD. Skin-derived precursors generate myelinating Schwann cells for the injured and dysmyelinated nervous system. J Neurosci. 2006 Jun 14;26(24):6651-60.

Pdf 3
Brederlau A, Correia AS, Anisimov SV, Elmi M, Paul G, Roybon L, Morizane A, Bergquist F, Riebe I, Nannmark U, Carta M, Hanse E, Takahashi J, Sasai Y, Funa K, Brundin P, Eriksson PS, Li JY. Transplantation of human embryonic stem cell-derived cells to a rat model of Parkinson´s disease: effect of in vitro differentiation on graft survival and teratoma formation. Stem Cells. 2006 Jun;24(6):1433-40.

Pdf 4
Pineda JR, Rubio N, Akerud P, Urban N, Badimon L, Arenas E, Alberch J, Blanco J, Canals JM. Neuroprotection by GDNF-secreting stem cells in a Huntington´s disease model: optical neuroimage tracking of brain-grafted cells. Gene Ther. 2006 Aug 31

Pdf 5
Jin K, Galvan V, Xie L, Mao XO, Gorostiza OF, Bredesen DE, Greenberg DA.
Enhanced neurogenesis in Alzheimer´s disease transgenic (PDGF-APPSw,Ind) mice. Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13363-7.

Pdf 6
Tsai PT, Ohab JJ, Kertesz N, Groszer M, Matter C, Gao J, Liu X, Wu H, Carmichael ST. A critical role of erythropoietin receptor in neurogenesis and post-stroke recovery. J Neurosci. 2006 Jan 25;26(4):1269-74.

Pdf 7
Molofsky AV, Pardal R, Iwashita T, Park IK, Clarke MF, Morrison SJ. Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature. 2003 Oct 30;425(6961):962-7. Epub 2003 Oct 22.

Pdf 8
Pluchino S, Quattrini A, Brambilla E, Gritti A, Salani G, Dina G, Galli R, Del Carro U, Amadio S, Bergami A, Furlan R, Comi G, Vescovi AL, Martino G. Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis. Nature. 2003 Apr 17;422(6933):688-94.

Pdf 9
Sanai N, Tramontin AD, Quinones-Hinojosa A, Barbaro NM, Gupta N, Kunwar S, Lawton MT, McDermott MW, Parsa AT, Manuel-Garcia Verdugo J, Berger MS, Alvarez-Buylla A. Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration. Nature. 2004 Feb 19;427(6976):740-4

Extra- pdf
Lopez-Toledano MA, Shelanski ML.
Neurogenic effect of beta-amyloid peptide in the development of neural stem cells.
J Neurosci. 2004 Jun 9;24(23):5439-44.

Most relevant publications of invited speakers and coordinators:

Allison Ebert
Behrstock S, Ebert A, McHugh J, Vosberg S, Moore J, Schneider B, Capowski E, Hei D, Kordower J, Aebischer P, Svendsen CN. (2006) Human neural progenitors deliver glial cell line-derived neurotrophic factor to parkinsonian rodents and aged primates. Gene Ther. 2006 Mar;13(5):379-88.
Ebert AD, Svendsen CN. (2005) A new tool in the battle against Alzheimer’s disease and aging: ex vivo gene therapy. Rejuvenation Research 8 (3): 131-134.
Ebert AD, Vincent L. Cryns, Feng Chen, Xiaolong He, Martha C. Bohn (2005). A tetracycline-regulated adenovirus encoding dominant-negative caspase-9 is regulated in rat brain and protects against neurotoxin induced cell death in vitro, but not in vivo. Experimental Neurology 191 Suppl 1:S80-94.

Mónica Mendes Sousa
Nunes AF, Saraiva MJ, Sousa MM (2006). Transthyretin knockouts are a new mouse model for increased neuropeptide Y. FASEB J. 20:166-8.
Sousa MM, Saraiva MJ (2003). Neurodegeneration in familial amyloid polyneuropathy: from pathology to molecular signaling. Progress in Neurobiology 71: 385-400.

Jia-Yi Li
Smith R, Brundin P, Li J.-Y (2005) Synaptic dysfunction in Huntington’s disease: a new perspective. Cell. Mol. Life Sci., 62:1901-1912.
Smith R, Chung H., Rundqvist S., Maat-Schieman M.L.C., Colgan L., Englund E., Liu Y.-J., R.A.C. Roos, Faull R.L.M., Brundin P, Li J.-Y. (2006) Cholinergic neuronal defect without cell death in Huntington’s disease. Hum. Mol. Genet., 15: 3119-3131.
Roybon L., Christophersen N., Brundin P, Li J.-Y. (2004) Stem cell therapy for Parkinson’s disease: Where do we stand?. Cell Tissue Res. 318:261-273.
Brederlau A.§, Correia A. S.§, Anisimov S.V., Elmi M., Paul G., Roybon L., Morizane A., Bergkvist P., Riebe I., Nannmark U., Carta M., Hanse E., Takahashi J., Sasai Y., Funa K., Brundin P., Eriksson P. S.#, Li J.-Y.# (2006) Transplantation of human embryonic stem cell-derived cells to a rat model of Parkinson’s disease: effect of in
vitro differentiation on graft survival and teratoma formation. Stem Cells, 24: 1433-1440.

João Bettencourt Relvas
Leone DP, Relvas JB, Campos LS, Hemmi S, Brakebusch C, Fassler R, Ffrench-Constant C, Suter U. (2005) Regulation of neural progenitor proliferation and survival by beta1 integrins. J Cell Sci. 118(Pt 12):2589-99.
Benninger Y, Colognato H, Thurnherr T, Franklin RJ, Leone DP, Atanasoski S, Nave KA, Ffrench-Constant C, Suter U, Relvas JB. (2006) Beta1-integrin signaling mediates premyelinating oligodendrocyte survival but is not required for CNS myelination and remyelination. J Neurosci. 26(29):7665-73.
Thurnherr T, Benninger Y, Wu X, Chrostek A, Krause SM, Nave KA, Franklin RJ, Brakebusch C, Suter U, Relvas JB. (2006) Cdc42 and Rac1 signaling are both required for and act synergistically in the correct formation of myelin sheaths in the CNS. J Neurosci. 26(40):10110-9.
Campos LS, Leone DP, Relvas JB, Brakebusch C, Fassler R, Suter U, ffrench-Constant C. (2004) Beta1 integrins activate a MAPK signalling pathway in neural stem cells that contributes to their maintenance. Development. 131(14):3433-44.

Araújo IM, Verdasca MJ, Leal EC, Bahr BA, Ambrósio AF, Carvalho AP, Carvalho CM (2004) Early calpain-mediated proteolysis following AMPA receptor activation compromises neuronal survival in cultured hippocampal neurons. Journal of Neurochemistry 91(6): 1322-31.

Araújo IM, Xapelli S, Gil JMAC, Mohapel P, Petersén Å, Pinheiro PS, Malva JO, Bahr BA, Brundin P, Carvalho CM (2005) Proteolysis of NR2B by calpain in the hippocampus of epileptic rats. Neuroreport 16(4): 393-6.

Araújo IM, Carvalho CM (2005) Role of nitric oxide and calpain activation in neuronal death and survival. Current Drug Targets CNS Neurological Disorders 4:319-324. Review

Gil J*, Mohapel P*, Araújo IM, Popovic N, Li J-Y, Brundin P, Petersén Å. (2005) Reduced hippocampal neurogenesis in R6/2 transgenic Huntington’s disease mice. Neurobiology of Disease 20(3): 744-751.

Almeida S, Domingues A, Rodrigues L, Oliveira CR, Rego AC (2004) FK506 prevents mitochondrial-dependent apoptotic cell death induced by 3-nitropropionic acid in rat primary cortical cultures. Neurobiol Dis. 17: 435-444.

Rego AC, de Almeida LP (2005) Molecular targets and therapeutic strategies in Huntington´s disease. Curr Drug Targets CNS Neurol Disord. 4: 361-381. Review

Oliveira JM, Chen S, Almeida S, Riley R, Goncalves J, Oliveira CR, Hayden MR, Nicholls DG, Ellerby LM, Rego AC (2006) Mitochondrial-dependent Ca2+ handling in Huntington´s disease striatal cells: effect of histone deacetylase inhibitors. J Neurosci. 26: 11174-11186.

Duarte AI, Proenca T, Oliveira CR, Santos MS, Rego AC (2006) Insulin restores metabolic function in cultured cortical neurons subjected to oxidative stress. Diabetes. 55: 2863-2870.
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