Aluminum alters NMDA receptor 1A and 2A/B expression on neonatal hippocampal neurons in rats

Abstract

BackgroundHigh aluminum (Al) content in certain infant formula raises the concern of possible Al toxicity on brain development of neonates during their vulnerable period of growing. Results of in vivo study showed that Al content of brain tissues reached to 74 μM when oral intake up to 1110 μM, 10 times of that in the hi-Al infant formula.MethodsUtilizing a cultured neuron cells in vitro model, we have assessed Al influence on neuronal specific gene expression alteration by immunoblot and immunohistochemistry and neural proliferation rate changes by MTT assay.ResultsMicroscopic images showed that the neurite outgrowth of hippocampal neurons increased along with the Al dosages (37, 74 μM Al (AlCl3)). MTT results also indicated that Al increased neural cell viability. On the other hand, the immunocytochemistry staining suggested that the protein expressions of NMDAR 1A and NMDAR 2A/B decreased with the Al dosages (p < 0.05).ConclusionTreated hippocampal neurons with 37 and 74 μM of Al for 14 days increased neural cell viability, but hampered NMDAR 1A and NMDAR 2A/B expressions. It was suggested that Al exposure might alter the development of hippocampal neurons in neonatal rats.

A Modified Technique for Culturing Primary Fetal Rat Cortical Neurons

“…Some protocols say to dissect the cerebral cortex in cold PBS or HBSS [ 2 , 3 ]. The dissection of the pia mater and blood vessels can take considerable time, and the metabolism of fetal rat neurons is very robust.…”

Aluminum overload increases oxidative stress in four functional brain areas of neonatal rats

“…The main route of Al excretion is the urine; therefore, subjects with kidney malfunction or immature kidney, such as nephropathy patients or neonates, might experience toxic accumulation of Al in the body [ 12 ]. Infant formula is the primary food source for bottle-fed neonates.…”

“…Infant formula is the primary food source for bottle-fed neonates. The study of Yuan et al reviewed several other studies and reported that most commercial infant formulas contained higher Al (6.5 μM to 87 μM) than human breast milk (0.2 μM to 1.7 μM) [ 12 ]. Infants display rapid growth and their brain-blood-barrier, detoxification system (liver), and excretory system (kidney) are not well-developed [ 13 , 14 ].…”

“…The group’s previous study with Al treatment in neonatal rat hippocampal neurons at concentrations of 37 μM and 74 μM for 14 days significantly reduced NMDAR (N-methyl-D-aspartate receptor) expression which was used as a marker of brain development. This suggested that Al exposure might influence the development of hippocampal neurons in neonatal rats [ 12 ].…”

“…In previous studies on adult animals, Al induced the production of ROS and caused oxidative damage in the brain [ 3 - 11 ]. Neonatal animal studies also identified that Al exposure during gestation and lactation periods induced brain developmental deficits in pups [ 12 , 16 , 17 ]. Thus, the hypothesis of the present study was that ROS might be the cause of developmental damage in the neonatal brain following Al administration.…”