Zinc Deficiency Is Associated with Increased Brain Zinc Import and LIV-1 Expression and Decreased ZnT-1 Expression in Neonatal Rats

Abstract

Zinc (Zn) deficiency has been associated with adverse behavioral outcomes in infants and children. However, Zn deficiency does not affect brain Zn concentration, suggesting that brain Zn homeostasis is tightly regulated. The recent identification of Zn-specific transport proteins allowed us to examine effects of low Zn intake on tissue Zn level, brain Zn uptake, and zinc transporter expression and localization in neonatal rat brain. Female rats were fed diets differing only in Zn content [7, moderately zinc deficient (ZD); 10, marginally zinc deficient (MZD); or 25 mg Zn/kg, control] and pups were killed on postnatal d 11. Plasma and brain Zn concentrations were measured, brain Zn uptake was assessed using (65)Zn, brain metallothionein-I and -III; LIV-1, zinc transporter ZnT-1, and ZnT-3 expression was measured by semiquantitative RT-PCR. LIV-1 localization in the brain was determined by immunohistochemistry; brain and hippocampi LIV-1 and ZnT-1 protein expressions were measured by Western blotting. Plasma Zn concentration was lower in MZD and ZD pups, whereas brain Zn concentration was not affected. Brain Zn uptake was higher in MZD and ZD rats compared with controls. Metallothionein-I and ZnT-1 expressions were lower and LIV-1 expression was higher in the whole brain of MZD and ZD pups. Metallothionein-III and ZnT-3 mRNA expressions were not affected. LIV-1 was localized to the plasma membrane of many brain cell types, including hippocampal pyramidal neurons and the apical membrane of the choroid plexus. Our results indicate that Zn deficiency results in alterations in Zn transporter expression, which facilitates increased brain Zn uptake and results in the conservation of brain Zn during Zn deficiency.