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Mapping the pattern of expression of c-fos and definition of refractory period in marmoset´s brain(Callithrix jacchus) after stimulation with pentylenetetrazol (PTZ)

Grant number: 12/15562-1
Support type:Scholarships in Brazil - Master
Effective date (Start): November 01, 2012
Effective date (End): April 30, 2014
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Luiz Eugenio Araujo de Moraes Mello
Grantee:Vanessa Novaes Barros
Home Institution: Pró-Reitoria de Pós-Graduação e Pesquisa. Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil


When neurons are intensely activated provokes synthesis of specific proteins that requires activation of immediate expression genes, which the best known is c-fos.This gene is related to neuronal activation and its expressed in situations when the animal is exposed to new situations.Several studies with mice and rats showed expression of c-fos in various regions of the central nervous system such as the dentate gyrus, CA1, CA2, CA3, thalamus, piriform cortex, cingulate gyrus, amygdala, visual cortex, olfactory bulb, cranial nerves, cerebellum, striatum among other brain structures when the animal is exposed to a wide range of stimuli (water stress, fear, odors, intraparenchymal injection of various substances, etc.).The primary studies about the pattern of expression of c-fos used pentylenetetrazol (PTZ) as a stimulus.In rats and mice, it is known that after the injection of PTZ the gene expression would increase gradually reaching a maximum levels around 1hour after stimulation. subsequently, the expression decreases to baseline. There is controversy about the moment that c-fos returns to baseline, there are studies indicating 6h (Chaudihuri et al., 2000), 17h (Morgan et al., 1987), 48h (Bisler et al., 2002) and 5 days.However, all authors assert that a second stimulus only triggers the same increase in gene expression after the level of c-fos returns to baseline.Before that, the expression is lower or zero, characterizing the refractory or semi-refractory period.The kindling is a technique which the application of various stimuli subconvulsivantes results for several days in seizures even with the same dose subconvulsivante. It is known that it is possible to induce this phenomenon (of kindling) in rodents, but there are doubts about its induction in primates. We have a hypothesis that the stimuli for the induction of kindling would not assume the refractory period of c-fos in primates (based on preliminary data from our laboratory).Based on that, we believe that the profile of expression of c-fos in primates may be different from that of rodents. There are few studies abording this aspect of gene expression, we found only Kazi et al., 2003 which showed peak expression of c-fos at 6 h which decreased around by 42 and 72 in the visual cortex. However, the returning to baseline values and the refractory period was not consedered. Most important, this work does not discuss the interesting question of what biochemical differences (and not just anatomical differences) between primates and rodents may contribute to differences in memory and learning among these families.This research aims to draw a profile of expression of c-fos through stimulation in rats with PTZ (for comparison - control group) and monkeys in various regions of the central nervous system, in order to provide this pattern as widely as possible . Furthermore, we will attempt to identify the refractory period of c-fos in both animals.