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Role of astrocytes in synaptic and memory dysfunction in Alzheimers disease
Portugal (PorMSIC) - University of Coimbra, Coimbra
Rodrigo. A. Cunha.
Type of Research Project
- Basic science
What is the background of the project?
The concept of tripartite synapse includes astrocytes, the largest cell population in human brain, as key players in synaptic plasticity, the purported neurophysiological basis of memory. However the possible role of astrocytes in early Alzheimer s disease (AD) is still be unraveled, albeit the shrinkage of astrocytes has been described in early AD. AD is characterized by a progressive memory deterioration, which is associated to synaptic dysfunction and loss likely triggered by amyloid-beta (AB) oligomers. We posit that astrocytic modifications are responsible for bolstering synaptic dysfunction and loss resulting in the emergence of short-term memory deficits characteristic of early AD phases.
What is the aim of the project?
In this project, we aim to define the impact of astrocytic function on synaptic morphology and function in physiological and AD conditions.
What techniques and methods are used?
It will be use: stereotaxic surgery in mouse to administrated compounds intracereberally; animal behavioral test, mainly to assess cognitive function electrophysiological studies to gauge synaptic plasticity; immunohistochemistry with observation using epifluorescence and confocal microscopy; Western-blot analysis.
What is the role of the student?
- The student will observe the practical experiments but will be highly involved in the analysis of the results
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
It is expected that the student learn the techniques described above, such as stereotaxic surgery in mouse to administrated compounds intracereberally, animal behavioral test, mainly to assess cognitive function electrophysiological studies to gauge synaptic plasticity, immunohistochemistry with observation using epifluorescence and confocal microscopy, western-blot analysis, and also perform it always under supervision. Moreover, it is expected that the student is motivated, have a critical spirit, contributing to developing of the work. Moreover, it is expected that him/her knows to work in team and complies with the rules.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
The students will have access to several bibliographies. There are seminars about biomedical sciences (at least one) weekly in our researcher center. Our research group has weekly meetings, where results and papers (journal club) are presented and discussed. Depending on the date, of the training period, might exist doctoral or masters courses happening
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 - 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
- M; Shen HY; Augusto E; Wang Y; Wei CJ; Wang YT; Agostinho P; Boison D;Cunha RA; Chen JF. (2015) Deletion of Adenosine A(2A) Receptors from Astrocytes Disrupts Glutamate Homeostasis Leading to Psychomotor and Cognitive Impairment: Relevance to Schizophrenia. Biol Psychiatry. 2015 Feb 27. pii: S0006-3223(15)00151- 1. doi:0.1016/j.biopsych.2015.02.026.
- Rodrigues DI; Gutierres J; Pliassova A; Oliveira CR; Cunha RA; Agostinho P. (2014) Synaptic and sub-synaptic localization of amyloid-B protein precursor in the rat hippocampus. J Alzheimers Dis. 40:981-92. doi: 10.3233/JAD-132030.
- Matos M; Augusto E; Agostinho P; Cunha RA; Chen JF. (2013) Antagonistic interaction between adenosine A2A receptors and Na+/K+-ATPase-a2 controlling glutamate uptake in astrocytes. J Neurosci. 33(47):18492-502 (Q1) doi:10.1523/JNEUROSCI.1828-13.2013.
- Matos M; Augusto E; Machado NJ; dos Santos-Rodrigues A; Cunha RA; Agostinho P. (2012) Astrocytic adenosine A2A receptors control the amyloid-B peptide-induced decrease of glutamate uptake. J Alzheimers Dis. 31(3):555-67 (Q2) doi: 10.3233/JAD- 2012-120469.
- Matos M; Augusto E; Santos-Rodrigues AD; Schwarzschild MA; Chen JF; Cunha RA; Agostinho P. (2012) Adenosine A2A receptors modulate glutamate uptake in cultured astrocytes and gliosomes. Glia. 60(5):702-16 (Q1) doi: 10.1002/glia.22290.
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