Oxidative stress, behavior, and epigenetic modifications in an animal model of hyperhomocysteinemia

• Grant number: 11/15699-4
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2012
• End date: February 28, 2014
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Vânia D'Almeida
• Grantee: Marina Mastelaro de Rezende
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Increased plasma homocysteine seems to be a risk factor for cardiovascular disease, as well as neuropsychiatric and cognitive disorder. Among the mechanisms we can mention secondary biochemical changes responsible for these processes. The balance in the redox state can be mentioned because the homocysteine itself has the feature to oxidize and thus, provide an increased formation of oxidative compounds such as hydrogen peroxide, superoxide anion and, indirectly, malonic dialdehyde. Despite this evidence, knowledge about the pathways responsible for behavioral consequences associated with hyperhomocysteinemia has not been determined, nor in cases of moderate increases, or in severe forms of homocystinuria, in which mental retardation may be present in childhood and in adulthood, even in patients without cognitive impairment, may lead to psychiatric disorders such as depression. Epigenetic modifications are presented as a possible mechanism in determining cognitive-behavioral changes in individuals with increased homocysteine levels. This is because one of the most important changes in DNA is methylation of cytosines and this occurs at the expense of the methionine metabolic pathway, in which the product is homocysteine. Consequently, genetic and environmental factors (especially dietary) may also occupy an important role. Moreover, considering the link between the cognitive processes of BDNF (brain derived neurotrophic factor), it is interesting to study its involvement in cases of hyperhomocysteinemia. Thus, the objective of the study is to analyze how the increase in plasma homocysteine influences cognitive functions, considering the biochemical and epigenetic changes resulted from this accumulation in mice, in order to reduce the interfering variables such as genetic and environmental factors. (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)

DE REZENDE, MARINA MASTELARO; D'ALMEIDA, VANIA. Central and Systemic Responses to Methionine-Induced Hyperhomocysteinemia in Mice. PLoS One, v. 9, n. 8, AUG 25 2014. (10/00075-2, 11/15699-4)