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ToxSci Advance Access originally published online on March 25, 2009
Toxicological Sciences 2009 109(2):286-295; doi:10.1093/toxsci/kfp062
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© The Author 2009. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Selective Brain Uptake and Behavioral Effects of the Cyanobacterial Toxin BMAA (β-N-Methylamino-L-alanine) following Neonatal Administration to Rodents

Oskar Karlsson*, Nils Gunnar Lindquist*,{dagger}, Eva B. Brittebo*,1 and Erika Roman*

* Department of Pharmaceutical Biosciences, Uppsala University, 751 24 Uppsala, Sweden {dagger} Swedish Chemicals Agency, 172 13 Sundbyberg, Sweden

1 To whom correspondence should be addressed at Uppsala University, Department of Pharmaceutical Biosciences, Box 594, SE-751 24 Uppsala, Sweden. Fax: +46-18-4714253. E-mail: Eva.Brittebo{at}farmbio.uu.se.

Received January 30, 2009; accepted March 20, 2009


  Abstract

Cyanobacteria are extensively distributed in terrestrial and aquatic environments all over the world. Most cyanobacteria can produce the neurotoxin β-N-methylamino-L-alanine (BMAA), which has been detected in several water systems and could accumulate in food chains. The aim of the study was to investigate the transfer of BMAA to fetal and neonatal brains and the effects of BMAA on the development of behavioral characteristics during the brain growth spurt (BGS) in rodents. Pregnant and neonatal mice were given an injection of 3H-BMAA on gestational day 14 and postnatal day (PND) 10, respectively, and processed for tape-section autoradiography. The study revealed transplacental transfer of 3H-BMAA and a significant uptake in fetal mouse brain. The radioactivity was specifically located in the hippocampus, striatum, brainstem, spinal cord and cerebellum of 10-day-old mice. The effect of repeated BMAA treatment (200 or 600 mg/kg sc) during BGS on rat behavior was also studied. BMAA treatment on PND 9–10 induced acute alterations, such as impaired locomotor ability and hyperactivity, in the behavior of neonatal rats. Furthermore, rats given the high dose of BMAA failed to habituate to the test environment when tested at juvenile age. In conclusion, the results demonstrated that BMAA was transferred to the neonatal brain and induced significant changes in the behavior of neonatal rats following administration during BGS. The observed behavioral changes suggest possible cognitive impairment. Increased information on the long-term effects of BMAA on cognitive function following fetal and neonatal exposure is required for assessment of the risk to children's health.

Key Words: neurotoxin; ALS/PDC; hippocampus; striatum; brain growth spurt; seizure.


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O. Karlsson, E. Roman, and E. B. Brittebo
Long-term Cognitive Impairments in Adult Rats Treated Neonatally with {beta}-N-Methylamino-L-Alanine
Toxicol. Sci., November 1, 2009; 112(1): 185 - 195.
[Abstract] [Full Text] [PDF]


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