Effects of chronic phospholipase A2 inhibition on the differentiation of new neurons in brain mature cells of adult rats

• Grant number: 09/53008-3
• Support Opportunities: Research Grants - Young Investigators Grants
• Duration: February 01, 2010 - January 31, 2014
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Evelin Lisete Schaeffer
• Grantee: Evelin Lisete Schaeffer
• 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 scholarship(s): 13/00100-5 - Effects of lithium on the proliferation and migration of neuroblasts in the rostral migratory stream in adult mice, BP.IC; 11/24022-8 - Combined effect of lithium and environmental enrichment on the survival of new cells in the hippocampus of adult mice, BP.IC; 11/23039-4 - Combined effect of lithium and environmental enrichment on the survival of new cells in the hippocampus of adult mice, BP.IC; 10/05442-3 - Effects of chronic phospholipase A2 inhibition on the differentiation of new neurons into mature cells in the brain of adult rats, BP.JP

Abstract

With the discovery that constitutive neurogenesis persists in the adult mammalian brain, has emerged the hypothesis in the literature that Alzheimer disease (AD) could be overcome, or at least ameliorated, since the generation of new neurons might help to compensate for the loss of neurons in the disease. In fact, the neuroproliferation is increased in the AD brain, but the new neurons fail to differentiate into mature cells. There are evidences that the activity of the phospholipase A2 (PLA2) enzyme is reduced in the brain of subjects with AD, and that the PLA2 participates directly in the neurite extension in vitro and indirectly in the maturation of new neurons in vivo. We hypothesize that the inhibition of PLA2 in the AD brain may contribute to the failure in the maturation of new neurons. The objective of this project is to investigate the direct relationship between the PLA2 and the process of differentiation into mature neurons in vivo. Adult rats will receive intraperitoneal injection of BrdU (marker of proliferating cells) and will be killed 28 days later by intracardiac perfusion for fixation of brain tissue, which will be cut in cryostat. Twenty-eight days post-BrdU, 12 naive rats will be killed to serve as a reference to cell proliferation in sections labeled for BrdU, and to cell differentiation in sections labeled with fluorescence for BrdU and NeuN (neurons) or GFAP (glia). Moreover, 15 days post-BrdU, 36 rats will be operated, of which 12 will receive intracerebroventricular infusion of a PLA2 inhibitor (MAFP) for 7 days, 12 will receive infusion of a vehicle (DMSO/saline) for 7 days, and 12 will not receive any drug (sham rats). All operated animals will be killed 28 days post-BrdU to investigate neuronal and glial differentiation; cell proliferation will also be investigated in these animals as a criterion for selection. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SCHAEFFER, EVELIN L.; CERULLI, FABIANA G.; SOUZA, HELIO O. X.; CATANOZI, SERGIO; GATTAZ, WAGNER F.. Synergistic and additive effects of enriched environment and lithium on the generation of new cells in adult mouse hippocampus. JOURNAL OF NEURAL TRANSMISSION, v. 121, n. 7, p. 695-706, JUL 2014. (11/24022-8, 09/52825-8, 09/53008-3, 11/23039-4)

SCHAEFFER, EVELIN L.; GATTAZ, WAGNER F.. Chronic inhibition of brain phospholipase A(2) in adult rats impairs the survival of newborn mature neurons in the hippocampus. JOURNAL OF NEURAL TRANSMISSION, v. 122, n. 5, p. 619-628, MAY 2015. (09/52825-8, 09/53008-3, 10/05442-3)