Oral aluminum administration during pregnancy and lactation produces gastric and renal lesions in rat mothers and delay in CNS development of their pups.

Abstract

The expression of the neurofilament protein of the highest molecular weight (NF-H) is developmentally and spatially regulated. For example, the MAb RMO24.9, directed against a phosphorylated epitope in the tail domain of NF-H, immunohistochemically labels specific tracts within the rat brainstem prenatally, but does not label diencephalic tracts until after postnatal day 10 (P10). A diet providing 300 mg/kg/d Al (as Al lactate) to rat dams throughout gestation causes behavioral deficits in their offspring (Bernuzzi et al., 1989). We repeated this regimen by substituting 120 mM Al lactate (pH 6.5) for drinking water during gestation and lactation, and examined the distribution of immunolabeling by RMO 24.9 after exposure to Al. Tracts within the diencephalon that bind RMO 24.9 on P11 in control pups did not bind the MAb until P14 in Al-treated pups. In these preliminary experiments, Al seemed to have caused a developmental delay in the expression of phosphorylated NF-H in the pups of mothers that received Al during gestation. However, subsequent experiments showed that the neuropathology observed--and that reported by other investigators using similar Al levels--may not be the result of the direct effects of Al on the pups. Throughout lactation, treated dams appeared progressively more cachexic. Unlike the normal viscera of pair-watered controls, the stomachs of treated dams were ulcerated, and their kidneys had decreased cortical thickness and contained stones. Lesions such as these compromise a rat's ability to absorb nutrients, to excrete toxins, and to regulate water and electrolytes. In a lactating dam, these alterations could compromise the dam's ability to nourish her pups. Our experiments point out that the mechanisms of Al toxicity-- already complex in the adult--are further complicated in a system in which the pup is dependent on the mother for delivery of both nutrients and toxins. It is therefore impossible to determine the cause of any neuropathology in the pup in a system where Al delivery overlies a background of multisystem defect and altered maternal homeostasis.