Brain manganese accumulation is inversely related to γ-amino butyric acid uptake in male and female rats
Brain manganese accumulation is inversely related to γ-amino butyric acid uptake in male and female rats
复制标题
DOI：
10.1093/toxsci/kfl130
复制
发表时间：
2007-01-01
影响因子：
3.8
通讯作者：
Erikson, Keith M.
中科院分区：
文献类型：
--
作者：
Anderson, Joel G.;Cooney, Paula T.;Erikson, Keith M.
铁（Fe）是参与许多细胞过程的必需微量金属。据报道，缺铁（ID）是全球最普遍的营养问题。越来越多的证据表明，ID与神经递质代谢改变和锰（Mn）神经毒性的风险因素有关。虽然最近的研究已经建立了差异，其中女性大脑响应ID相关的神经化学变化与男性大脑，鲜为人知的是饮食ID，锰暴露和性别的相互作用对γ-氨基丁酸（GABA）。将雄性和雌性Sprague-Dawley大鼠随机分为4个饮食处理组：对照组（CN）、对照/ Mn补充组、ID组和ID/Mn补充组。治疗6周后，与CN相比，两种ID饮食均导致两种性别动物所有脑区的Fe浓度显著降低。ID和锰补充导致显着积累的锰在所有的大脑区域在两种性别。性别对铁、锰的积累无显著影响。利用纹状体突触体研究饮食干预对H-3-GABA摄取的影响。4周时，雄性大鼠铁浓度与H-3-GABA摄取量之间存在显著相关性（p < 0.05）。6周时，雄性和雌性大鼠Mn浓度与~ 3 H-GABA摄取呈显著负相关，雌性大鼠Fe浓度与~ 3 H-GABA摄取呈正相关（p < 0.05）。总之，ID相关的锰积累是相似的，在两种性别，锰水平影响GABA的吸收在两种性别的一个可比的方式。
Iron (Fe) is an essential trace metal involved in numerous cellular processes. Iron deficiency (ID) is reported as the most prevalent nutritional problem worldwide. Increasing evidence suggests that ID is associated with altered neurotransmitter metabolism and a risk factor for manganese (Mn) neurotoxicity. Though recent studies have established differences in which the female brain responds to ID-related neurochemical alterations versus the male brain, little is known about the interactions of dietary ID, Mn exposure, and sex on gamma-amino butyric acid (GABA). Male and female Sprague-Dawley rats were randomly divided into four dietary treatment groups: control (CN), control/ Mn supplemented, ID, and ID/Mn supplemented. After 6 weeks of treatment, both ID diets caused a highly significant decrease in Fe concentrations across all brain regions compared to CN in both sexes. Both ID and Mn supplementation led to significant accumulation of Mn across all brain regions in both sexes. There was no main effect of sex on Fe or Mn accumulation. Striatal synaptosomes were utilized to examine the effect of dietary intervention on H-3-GABA uptake. At 4 weeks, there was a significant correlation between Fe concentration and H-3-GABA uptake in male rats (p < 0.05). At 6 weeks, there was a significant inverse correlation between Mn concentration and 3H-GABA uptake in male and female rats and a postitive correlation between Fe concentration and H-3-GABA uptake in female rats (p < 0.05). In conclusion, ID-associated Mn accumulation is similar in both sexes, with Mn levels affecting GABA uptake in both sexes in a comparable fashion.