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Functional correlates of adult hippocampal cytogenesis: a matter of sex and time
Portugal (PorMSIC) - University of Minho, Braga
Life and Health Sciences Research Institute (ICVS) Universidade do Minho Campus de Gualtar
António Mateus-Pinheiro and Luísa Pinto
Type of Research Project
- Basic science
What is the background of the project?
Along with the subependymal-olfactory bulb system, the hippocampus is one of the two regions of the adult brain that retains the ability to generate new cells throughout life. Indeed, within the hippocampal dentate gyrus, neural stem cells (NSCs) have the ability to continuously generate new neuronal or astroglial cells, in a process called neurogenesis or astrogliogenesis, respectively. The complexity of this subject emerges primarily from the difficulty to precisely segregate the function of newborn cells from the preexisting neuron-glia cell network in which they are integrated. To better dissect the functional roles of new hippocampal cells, we will use the transgenic GFAP-Tk rat model to specifically ablate GFAP-expressing NSCs in the adult mammalian brain. We will then perform a longitudinal characterization of the impact of cytogenesis ablation in different emotional and cognitive behavioral dimensions, addressing the differential role of immature vs mature newborn cells, the impact of gender and menstrual phases.
What is the aim of the project?
The aim of the project is to induce cytogenesis ablation in GFAP-Tk adult male and female rats in order to explore the functional consequences of cytogenesis ablation in different behavioral test paradigms
What techniques and methods are used?
The project will start with the treatment of GFAP-TK transgenic adult female rats treated with ganciclovir to abrogate cytogenesis. Then, we will do a behavioral analysis to reveal the impact of cytogenesis suppression on anxiety-like behavior, anhedonic and depressive-like behaviors. We will also take in consideration the menstrual phases and it's influence on this factors. We will analyze blood corticosterone levels and expression of glucocorticoid receptors in the hippocampal dentate gyrus will be measured in animals with suppressed cytogenesis through imunohistochemistry and PCR. The project will also use the following techniques genotyping, 3D cell morphology analysis using Golgi-Cox analysis; in order to assess the full impact of cytogenesis ablation in different behavioral test paradigms.
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?
The student will start with some lectures about Neuroscience, the techniques and the previous work related to this project. Depending on the student, his/her knowledge and the stage of the project, he/she is expected to be able to work with GFAP-TK transgenic adult female rats, analysed the impact of cytogenesis suppression on the subjects and measure blood corticosterone levels and measure the expression of glucocorticoid receptors through imunohistochemistry and PCR in the hippocampal dentate gyrus through suppressed cytogenesis.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Students will assist to seminars of the Neuroscience domain every week and to all lectures that will happen. There will be also group meetings every week to discuss the projects.
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 presentation - The student will prepare a scientific report
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Some knowledge in neuroscience and brain function
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students
- Mateus-Pinheiro; A.; Pinto; L.; Bessa; J.M.; Morais; M.; Alves; N.D.; Monteiro; S.; Patrício; P.; Almeida; O.F.; and Sousa; N. (2013). Sustained remission from depressive-like behavior depends on hippocampal neurogenesis. Transl Psychiatry Jan15;3:e210.
- Morais; M.; Patrício; P.; Mateus-Pinheiro; A.; Alves; N.D.; Machado-Santos; A.R.; Correia; J.S.; Pereira; J.; Pinto; L.; Sousa; N.; Bessa; J.M.* (2017). The modulation of adult neuroplasticity is involved in the mood-improving actions of atypical antipsychotics in an animal model of depression. Transl Psychiatry Jun 6;7(6):e1146
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