Neurotrophic Factors in normal and disease nervous system 2012

Type of class Lecture

Offered by Medical Neurosciences

Instructor Dr. Ana Luisa Pina

Schedule Tuesdays and Thursdays 17-19:30hrs (for a first session Friday January 27th at 17:00 and then open to agree to another convenient time for all the participants). The course would run from last week in January to first week in March.

Location Experimental Neurosurgery (seminar room at the Aschheim-Zondek-Haus, Virchowweg 21, Charité Campus Mitte, behind the Nervenklinik and the Neurowissenschaftliches Forschungszentrum (NWFZ)).

Contact Dr. Ana Luisa Pina ()

Target audience MSc and PhD, open to MedNeuro students and other programs

ECTS points 4

Organized by Dr. Ana Luisa Pina (send email)

Learning Outcome

In a broad sense, trophism may be defined as the process by which cells in our bodies provide information one another to help them to stay healthy throughout the organism’s life. Trophism also stands for nourishment, trophic interactions are then necessary for cells to multiply, grow, survive, differentiate and maintain their morpho-functional integrity. Whereas changing trophic interactions may lead to the structural and functional reorganization of a cell system, the property that is also called plasticity, exaggerated decrements or increments of the levels of trophism could lead to cell death and therefore to pathological states. Hence, restoring the levels of trophism among the cells of our bodies lies at the heart of the therapeutics of many diseases that affect us.

This course deals with the concept of trophism. We will emphasize the actions of soluble messengers, collectively called growth or trophic factors, on various aspects of cell survival, differentiation, growth, disease and therapeutics. Although in this course we will mostly talk about protein messengers, we will also explore the diverse nature of other molecules capable of providing trophic information among cells. Thus amino acid transmitters, amino acid derivatives, hormones, extracellular matrix molecules, glyco-conjugates, gas molecules as carbon monoxide, nitrogen based derivatives, are all part of the orchestra that fine tunes trophism among cells.

Although trophism is a general phenomenon in all our cells, we will focus on the participation of trophic signals in health and disease of the nervous system. This is not only explained because this course is part of our Medical Neuroscience program, or because of our shared passion for trying to understand how our fascinating cephalic black box is organized, but also because the study of trophism has a long story in the neurosciences. In fact, it was the postulation of trophism by Santiago Ramony Cajal in the late eighteen hundreds, the re-discovery of trophism by the concepts generously provided by Viktor Hamburger, the discovery of the nerve growth factor by Rita Levi-Montalcini, and the development of the ecological view of neuronal development based upon competition, what furnished, triggered and still embraces most of the work carried out on trophism around the world.

Without pretending to cover exhaustively the large list of factors with trophic effects on the nervous system, we will concentrate to review a number of the most well known neurotrophic factors, as well as we will dedicate time to explore some of the recent discoveries on these interesting molecules.

Structure

Two weekly 3hrs classes will consist of 90mins. lectures, 10 minutes rest and then 60–90 min. analysis of literature related to the specific theme of the day (normally 3 papers, at least one review and two experimental, previously assigned by the lecturer). The students will present in 10–15 minutes one of the papers, with 5 minutes discussion and questions on the paper.

Participation in the class (at least 2–3 paper presentations, power point) and weekly written examination from the previous 2 sessions will be the evaluatory instruments.

Organizatory meeting (Friday Jan. 20th, 2012)

Trophism and the Neurotrophic factor hypothesis
Principles of cell signalling and trophic factors
The Neurotrophins: members, receptors and cell signalling
Neurotrophins and pathological states of the nervous system
FGF and EFG and adult neural stem cells niche
Insulin-like growth factors
Glial derived growth factors and Transforming Growth Factors
The Neurovascular link I: the neurotrophic effects of angiogenic and anti-angiogenic factors: PEDF, PDGF and VEGF
The Neurovascular link II: Erythropoietin
Neurotransmitters with neurotrophic function
Chemokines: the neuro-immune connection.

Assigments/Exams

Participation in the class (at least 2–3 paper presentations, power point) and weekly written examination from the previous 2 sessions will be the evaluatory instruments.

Readings

Mandatory

Principles of Neural Sciences. Kandel, Schwartz, Jessel. 4th Edition.

Chapter 53 “The generation and survival of Nerve cells”

Chapter 54 “The guidance of axons to their targets”

Chapter 55 “The formation and regeneration of Synapses”

Further

The literature will be assigned for each session. As examples:

Skaper SD.The biology of neurotrophins, signalling pathways, and functional peptide mimetics of neurotrophins and their receptors. CNS Neurol Disord Drug Targets. 2008 Feb;7(1):46–62.

Chao MV, Rajagopal R, Lee FS. Neurotrophin signalling in health and disease. Clin Sci (Lond). 2006 Feb;110(2):167–73.

Chao MV. Neurotrophins and their receptors: a convergence point for many signaling pathways. Nat Rev Neurosci. 2003 Apr;4:299–309.

Zacchigna S, Lambrechts D, Carmeliet P. Neurovascular signalling defects in neurodegeneration. Nat Rev Neurosci. 2008 Mar;9(3):169–81.

Lok J, Gupta P, Guo S, Kim WJ, Whalen MJ, van Leyen K, Lo EH. Cell-cell signaling in the neurovascular unit. Neurochem Res. 2007 Dec;32(12):2032–45.

Tombran-Tink J.The neuroprotective and angiogenesis inhibitory serpin, PEDF: new insights into phylogeny, function, and signaling. Front Biosci. 2005 Sep 1;10:2131–49.

Lazarovici P, Marcinkiewicz C, Lelkes PI. Cross talk between the cardiovascular and nervous systems: neurotrophic effects of vascular endothelial growth factor (VEGF) and angiogenic effects of nerve growth factor (NGF)-implications in drug development. Curr Pharm Des. 2006;12(21):2609–22.

Arcasoy MO. The non-haematopoietic biological effects of erythropoietin. Br J Haematol. 2008 Apr;141(1):14–31.

Balazs R. Trophic effect of glutamate. Curr Top Med Chem. 2006;6(10):961–8.

Spedding M, Gressens P. Neurotrophins and cytokines in neuronal plasticity. Novartis Found Symp. 2008;289:222–33