Effect of Vitamin B Deprivation during Pregnancy and Lactation on Homocysteine Metabolism and Related Metabolites in Brain and Plasma of Mice Offspring

Epidemiological and experimental studies indicate that the altered fetal and neonatal environment influences physiological functions and may increase the risk of developing chronic diseases in adulthood. Because homocysteine (Hcy) metabolic imbalance is considered a risk factor for neurodegenerative diseases, we investigated whether maternal Vitamin B deficiency during early development alters the offspring's methionine-homocysteine metabolism in their brain. To this end, the dams were submitted to experimental diet one month before and during pregnancy or pregnancy/lactation. After birth, the offspring were organized into the following groups: control (CT), deficient diet during pregnancy and lactation (DPL) and deficient diet during pregnancy (DP). the mice were euthanized at various stages of development. Hcy, cysteine, glutathione (GSH), S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), folate and cobalamin concentrations were measured in the plasma and/or brain. At postnatal day (PND) 0, total brain of female and male offspring exhibited decreased SAM/SAH ratios. Moreover, at PND 28, we observed decreased GSH/GSSG ratios in both females and males in the DPL group. Exposure to a Vitamin B-deficient diet during the ontogenic plasticity period had a negative impact on plasma folate and brain cortex SAM concentrations in aged DPL males. We also observed decreased plasma GSH concentrations in both DP and DPL males (PND 210). Additionally, this manipulation seemed to affect the female and male offspring differently. the decreased plasma GSH concentration may reflect redox changes in tissues and the decreased brain cortex SAM may be involved in changes of gene expression, which could contribute to neurodegenerative diseases over the long term.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)AFIPUniversidade Federal de São Paulo, Dept Pediat, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychobiol, São Paulo, BrazilUniv São Paulo, Sch Pharmaceut Sci, São Paulo, BrazilUniv Pernambuco, Pediat Hematol & Oncol Ctr, Inst Biol Sci, Recife, PE, BrazilUniversidade Federal de São Paulo, Dept Pediat, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychobiol, São Paulo, BrazilFAPESP: 2010/00075-2Web of Scienc

Effects of a Vitamin B-deficient diet during pregnancy on total GSH, reduced GSH and GSSG concentrations, and GSH/GSSG ratios in the brain of offspring at PND 0.

<p>n = 6–8; PND  =  Postnatal day; CT  =  control; DP  =  deficient diet during pregnancy; GSH  =  glutathione; GSSG  =  oxidized glutathione. <i>t test</i>. Data are presented as the mean ± standard error.</p

Effects of a Vitamin B-deficient diet during pregnancy and pregnancy/lactation on plasma and brain cortex parameters in offspring at PND 28.

<p>n = 6–8; PND  =  postnatal day; CT  =  control; DP  =  deficient diet during pregnancy; DPL  =  deficient during pregnancy and lactation; Hcy  =  homocysteine; Cys  =  Cysteine; GSH  =  glutathione; GSSG  =  oxidized glutathione; SAM  =  S-adenosylmethionine; SAH  =  S-adenosylhomocysteine. <i>ANOVA</i>. Data are presented as the mean ± standard error. ^*Different from the CT group (<i>P</i>≤0.05). ^#Difference between DP and DPL groups (<i>P</i>≤0.05). <i>t test</i>, § Difference between female and male control (<i>P</i>≤0.05).</p

Plasma Hcy concentration in dams after twenty days on an experimental diet.

<p>n = 6–8; PND  =  Postnatal day; CT  =  control; DDD  =  dams in deficient diet. <i>t test</i>. Data are presented as the mean ± standard error. ^*<i>P</i>≤0.05.</p

Effects of a Vitamin B-deficient diet during pregnancy on SAM and SAH concentrations and SAM/SAM ratios in the brain of male offspring at PND 0.

<p>n = 6–8; PND  =  Postnatal day; CT  =  control; DP  =  deficient diet during pregnancy; SAM  =  S-adenosylmethionine; SAH  =  S-adenosylhomocysteine. <i>t test</i>. Data are presented as the mean ± standard error. ^*<i>P</i>≤0.05.</p