Neurobehavioral development following aluminum administration in infant rabbits

Aluminum (Al) is known to be a neurotoxic agent in some species, inducing neurofibrillary tangles, dendritic atrophy, and behavioral deterioration, and has been implicated as a possible agent in human Alzheimer's disease and dialysis dementia. This study was conducted to assess the neurotoxic effects of Al in infant rabbits, and to compare the effects to those previously observed to follow exposure in the adult animal. Aluminum tartrate (2 microM) or physiologic saline was injected into the right lateral ventricle of 2-day-old (day P3) New Zealand white rabbits. The animals were trained in a step-down active avoidance task on P12 and retested 1 day later. They were killed on P20, and their hippocampal CA1 pyramidal cells examined for neurofibrillary tangles or prepared with the rapid Golgi stain for an examination of dendritic development. Additional animals were similarly infused with 1 or 3 microM Al for qualitative and some quantitative observations. No overt neurologic signs were observed in the 1- or 2-microM groups, however, most of the 3-microM group died between P10 and P20. Although there were no significant differences between the 2-microM and control animals on either learning or retention of the active avoidance task, deficits in retention of the task were observed in the 3-microM group. Neurofibrillary tangles in CA1 pyramidal cells were observed with dosages of 1 microM and higher. In the 2-microM group, the pattern of dendritic arborization in CA1 pyramidal cells was consistent with that expected for cells retarded in their development. These results have implications in terms of developmental differences in the neurobehavioral effects of Al.