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Analysis of hippocampus during genesis and neural differentiation in rats programmed by protein restriction in utero : molecular study of subfields isolated by laser microdissection

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Agnes Lopes
Total Authors: 1
Document type: Doctoral Thesis
Institution: Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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There are several reasons why we have sought the best understanding of the changes caused by fetal programming. Among them are the fact that these changes have had evident repercussions on the health of populations. In addition, changes during embryonic and fetal development may be among the leading causes of metabolic and endocrine diseases such as obesity, hypertension, insulin resistance and cardiovascular disease. This is due to changes in ontogeny development, linked to the scheduled manifestation of changes in the morphological and functional development of organs and systems. Considering the fact that the structural development of the brain begins in the early days of the embryonic period and extends into the first years of life, alterations during critical periods of pre and postnatal development can be highly detrimental to the development of this structure. The hippocampus is a target structure for several changes from the maternal environment. Studies have shown that alterations during the prenatal period had influence on neurogenesis in the immature hippocampus, as well as remodeling of the dendrites of the CA3 region, with possible cognitive alterations. In addition, there are several neurotransmitter systems, as well as epigenetic alterations of neural development modulators, which may be implicated in the cause or consequence of this programming. Therefore, it is important to know in what exact periods the brain is more susceptible to these influences and what their repercussion on the hippocampal structure. Thus, this thesis aimed to evaluate the effects of maternal protein restriction on the hippocampus of offspring of male rats at 14 and 40 days postnatal. Female Wistar rats were submitted to a hypoprotein diet throughout pregnancy. In the offspring of males with 14 and 40 days of age, the expression of genes in the hippocampal subfields (CA1, CA3 and GD) that could be modulating the responses found in the gestational protein restriction models were analyzed. Our results showed that animals with 14 days of life undergoing gestational protein restriction had a significant decrease in the expression of DCX in GD and in CA3, of 5HT1A in GD and in CA1. Additionally, the study showed a significant increase of MR in CA3, but with a decrease in GD, Increase in CDKN1C in CA1, as well as in AT4 in CA1 and AT1 in CA3. At 40 days, we observed a significant increase of DCX in GD and a decrease of SOX in this same region. These results suggest that the development of neuronal circuits in the hippocampus is associated with distinct gene expression in the different anatomical regions of the hippocampus. Also, the sequence of events including cell proliferation, migration and differentiation are associated with this distinct gene expression. In addition, early morphological and functional hippocampal damage from gestational protein restriction may be related to temporary structural damage. These, however, appear to be reversed by modifications in gene expression that modulate the production of proteins and neurotransmitters involved in the cellular recovery of these cognitive areas of the hippocampus (AU)

FAPESP's process: 13/20539-1 - Analysis of the neural effects of in utero protein restriction in rats subjected or not to caloric overload: study parameters neuro-behavioral, morpho-functional molecular and during development in rats
Grantee:Agnes da Silva Lopes Oliveira
Support type: Scholarships in Brazil - Doctorate