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Behavioural and pathological examination of an accurate mouse model of Alzheimer’s disease
Estonia (EstMSA) - University of Tartu, Tartu
Pharmacology, SIME, RAVILA 19, Tartu 50411
Alexander Zharkovsky MD
Miriam A. Hickey PhD
Type of Research Project
- Basic science
What is the background of the project?
Alzheimer’s disease (AD) is the leading cause of dementia in the elderly population and the most common neurodegenerative disease worldwide. AD is incurable. Current treatments can only alleviate mild-moderate memory deficits for a short period of time. It is possible that by the time that patients present and are diagnosed, they have progressed too far in their disease. It is therefore critical to develop safe drugs that can prevent the development of AD and that can be taken safely by individuals who are otherwise healthy but who are at risk of developing AD. Curcumin has previously been shown to be safe in human AD patients; however, its bioavailability is limited.
What is the aim of the project?
The experiments that will be conducted as part of this project will examine the efficacy of improved delivery of curcuminoids on behaviour and neuropathology in a mouse model of AD.
What techniques and methods are used?
Within the first week: The student will be trained in basic rodent brain anatomy. The student will learn histochemical and immunohistochemical techniques necessary for examination of amyloid, gliosis and neurodegeneration in rodent brain.The student will learn behavioural techniques used for analysis of rodent behaviour (at no point will the student actually handle animals during this project: animal work will be strictly observational only). The student will learn how to use analysis software packages (Stereoinvestigator, ImageJ). The student will complete a brief review of relevant research articles. Subsequently: The student will examine neuropathology in a mouse model of Alzehimer's disease. The student will assist with behavioural analysis of a mouse model of Alzehimer's disease (strictly observational only with respect to rodent behavioural analysis).
What is the role of the student?
What are the tasks expected to be accomplished by the student?
Develop knowledge of: a)Rodent brain anatomy. The student will learn to recognize different nuclei within the brain using Paxinos atlas and online Allen brain atlas (https://portal.brain-map.org/. b)Histochemical staining. Student will learn standard techniques: Cresyl violet (Hickey et al. Neuroscience. 2008 157(1): 280–295); Congo red (Nat Protoc. 2006;1(3):1591-5), Fluorojade (Chen et al., 2016), Thioflavin S (standard protocol from https://www.alzforum.org) c)Immunohistochemical staining (NeuN, GFAP; as for Hickey et al. Neuroscience. 2008 Nov 11; 157(1): 280–295) d)Rodent behavioural assays (Morris water maze, Novel object recognition, Y maze, open field; Hickey et al. Neuroscience. 2008 Nov 11; 157(1): 280–295; Front Genet. 2014 Apr 23;5:88). e) ImageJ and Stereoinvestigator for analysis of amyloid load, gliosis and neurodegeneration in rodent brain. f)Excel and Prism (5.0) for graphing and statistical analysis.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
The student will be provided with published reviews and research articles on AD and curcumin.
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 scientific report - The student’s name will be mentioned in a future publication
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Graduated students (less than 6 months) - Pre-Medical students from the American-British system - Students in biomedical fields - Dental medicine students (IADS members)
- General review on AD: “Alzheimer’s disease” The Lancet 2016 Vol 388 Issue 10043 pp505-517
- Original paper on the rodent model of AD that will be used in this project: “Intraneuronal beta-amyloid aggregates; neurodegeneration; and neuron loss in transgenic mice with five familial Alzheimer's disease mutations: potential factors in amyloid plaque formation” J Neurosci. 2006 Vol 26 Issue 40 pp10129-40.
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