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Neuroplasticity during neurodegenerative process.
Federal University of Santa Catarina (UFSC)
Morphological Sciences Department Biology Science Center Universidade Federal de Santa Catarina Campus UniversitárioTrindade 88040-900 Florianopolis- SC- Brazil
Ana Paula MarzagãoCasadei
Patricia de Souza Brocardo
English, Portuguese, Spanish
Type of Research Project
- Basic science
What is the background of the project?
Huntington’s disease (HD) is a polyglutamine neurodegenerative disorder caused by an unstable expansion of CAG (Cytosine – Adenine – Guanine) repeats within the coding region of the HD gene. Although the abnormal protein is ubiquitously expressed throughout the organism, cell degeneration occurs mainly in the brain, particularly in the striatum and certain layers of the cortex. Motor disturbances, associated with the loss of voluntary movement coordination, are the classical symptoms of HD. The cognitive capacities are also severely affected during the course of the disease with the slowing of intellectual processes being the first sign of cognitive impairment in HD patients. The genetic predictability of HD makes it potentially the most tractable of the neurodegenerative diseases for early intervention with the optimum time for the introduction of disease- modifying therapies being prior to the onset of symptoms. However, despite the efforts of a growing international HD research community, there is still no cure or satisfactory treatment for this neurodegenerative disease. Given the devastating emotional costs of this disorder as well as the large financial burden these individuals impose upon society, developing a treatment regime for HD is a recognized priority.
What is the aim of the project?
To the best of our knowledge, there are currently no reports indicating alterations in the brain- derived neurotrophin factor (BDNF) expression in the hippocampus of yeast artificial chromosome (YAC) 128 Huntington’s disease mice. Thus, we will start by evaluating the levels of hippocampal total and mature BDNF in YAC128 mice throughout the course of the disease (i.e., from a pre-symptomatic to an end-stage) and their age-matched wild-type (WT) controls. We will then investigate whether increasing the bioavailability of this neurotrophin (by physical exercise) will rescue hippocampal dysfunction and cognitive deficits in early-symptomatic and symptomatic YAC128 mice.
What techniques and methods are used?
Evaluation of the Hippocampal Neurogenesis; we will evaluate the different stages of hipocampal neurogenesis: proliferation, migration, differentiation, and maturation. In order to make this evaluation the immunohistochemistry techniques with cell proliferation markers (ki-67 [Antigen Ki-67] and PCNA [Proliferating cell nuclear antigen]) and for neuronal differentiation (DCX [doublecortin])are applied. It consists in slice animal brain tissue and processes these slices using different antibodies/biomarkers. Each antibody/biomarker is specific for each stage of neurogenesis. After that each slice will be evaluated using microscopes and image software.
What is the role of the student?
- The student will mainly observe
- The student will observe the practical experiments but will be highly involved in the analysis of the results
What are the tasks expected to be accomplished by the student?
The student will take active part in the practical aspect of the project. He/she will learn about adult hippocampal neurogenesis. The student will evaluate the different stages of hipocampal neurogenesis: proliferation, migration, differentiation, and maturation. In order to make this evaluation the immunohistochemistry techniques are applied. It consists in slice animal brain tissue and processes these slices using different antibodies/biomarkers. The student will prepare tissue slices, immunohistochemistry technique and specific procedures for cell proliferation and differentiation. The student will participate on the weekly seminars and discussions about the laboratory procedures, as well as, to present a seminar with the results obtained by him/her during his/her period in the laboratory of Neuroplasticity.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student will prepare a poster - The student will prepare a presentation
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Dedication and enthusiasm!
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Pre-Medical students from the American-British system - Students in biomedical fields
- Neuron. 2011 May 26; 70(4): 687–702. doi:10.1016/j.neuron.2011.05.001. AdultNeurogenesis in theMammalianBrain: SignificantAnswersandSignificantQuestions Guo-li Ming andHongjun Song.
- Orphanet J RareDis. 2010; 5: 40. doi: 10.1186/1750-1172- 5-40. Huntington'sdisease: a clinicalreview. Raymund AC Roos.
- NeurobiologyofDisease Volume 26; 1; 2007; Pages 189–200. Phenotypicabnormalities in the YAC128 mouse modelof Huntington disease are penetrantonmultiplegenetic backgrounds andmodulatedbystrain. Jeremy M. Van Raamsdonk1; Martina Metzler1; Elizabeth Slow1; Jacqueline Pearson; Claudia Schwab; Jeffrey Carroll; Rona K. Graham; Blair R. Leavitt; Michael R. Hayden.
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