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Effects of lithium on the proliferation and migration of neuroblasts in the rostral migratory stream in adult mice

Grant number: 13/00100-5
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): April 01, 2013
Effective date (End): December 31, 2013
Field of knowledge:Biological Sciences - Morphology
Principal Investigator:Evelin Lisete Schaeffer
Grantee:Giancarlo de Mattos Cardillo
Host Institution: Instituto de Psiquiatria Doutor Antonio Carlos Pacheco e Silva (IPq). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Associated research grant:09/53008-3 - Effects of chronic phospholipase A2 inhibition on the differentiation of new neurons in brain mature cells of adult rats, AP.JP


The discovery of the occurrence of neurogenesis (birth of new neurons) in adult brains has led to the search for cellular therapy strategies for the treatment of neurodegenerative diseases, such as Alzheimer Disease. Neurogenesis in the adult brain occurs in two areas: (a) Subgranular Zone of the hippocampus and (b) Subventricular Zone of the lateral ventricles. From these neurogenic sites, the new neurons migrate toward their final targets in other brain areas where they differentiate and integrate into local circuits. We hypothesize that a therapy strategy in neurodegenerative diseases could be the mobilization of newborn neurons from their neurogenic sites to the location of the lesion, so that they would integrate into the impaired neural network, thus contributing to the improvement of its functions. Several studies have demonstrated that pharmacological treatment with lithium exerts effects on adult neurogenesis, stimulating the survival and maturation of new neurons generated in the adult rodent brain. The objective of this project is to investigate whether treatment with lithium promotes the increase of migratory neuroblasts using as parameter the Rostral Migratory Stream, which extends from the lateral ventricles to the Olfactory Bulb, for being the best described migratory pathway. C57BL/6 mice will be divided into two groups: (a) Control and (b) Treated with Lithium. The animals will be treated for 6 weeks and, at four different time points, i.e., 10 days, 7 days, 3 days and 1 day before the end of treatment, will receive an intraperitoneal injection of BrdU, a marker of cell proliferation. The animals will be sacrificed by intracardiac perfusion followed by fixation with 4% paraformaldehyde. The fixed and frozen brains will be cut in a cryostat, and adjacent serial sagittal sections containing the Rostral Migratory Stream will be immunohistochemically labeled for BrdU, for analysis of the number and mobilization of proliferative cells.(AU)

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