Dose-Dependent Adult Neurodegeneration in a Rat Model After Neonatal Exposure to β-N-Methylamino-L-Alanine.

Abstract

The link between neonatal BMAA exposure and neurodegeneration has recently been demonstrated in rodents. We therefore investigated the behavioral and histopathological dose response to BMAA administered as a single dose. We report here that exposure to a BMAA dose as low as 50mg/kg on PND 3 caused mild short-term behavioral alterations as well as beta-amyloid deposition together with neuronal loss in the hippocampus of adult rats. Additionally, all histopathological abnormalities and behavioral deficits that had been observed in a previous study in the brain and spinal cord tissue of rats exposed to 400mg/kg BMAA on PND 3 were also observed here in the brain and spinal cord tissue of male and female rats exposed to 100mg/kg BMAA at the same age, although the proteinopathy burdens and volume losses were lower. Both behavioral deficits and histopathology increased with increasing dose, and a single neonatal BMAA exposure at a dose of 100mg/kg was the lowest dose able to cause clinical signs of toxicity, behavioral deficits, and neuropathology that are typically observed in AD, PD, and/or ALS patients.