Dose-Dependent Adult Neurodegeneration in a Rat Model After Neonatal Exposure to β-N-Methylamino-l-Alanine
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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 50 mg/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 400 mg/kg BMAA on PND 3 were also observed here in the brain and spinal cord tissue of male and female rats exposed to 100 mg/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 100 mg/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.
Keywordsβ-N-methylamino-l-alanine BMAA Rats Behavior Neurodegeneration Dose response
This study was partly funded by the National Research Foundation of South Africa.
Compliance with Ethical Standards
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. And all procedures performed here involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. This article does not contain any studies with human participants performed by any of the authors.
Conflict of Interest
The authors declare that they have no conflict of interest.
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