Selective brain uptake and behavioral effects of the cyanobacterial toxin BMAA (beta-N-methylamino-L-alanine) following neonatal administration to rodents.
Cyanobacteria are extensively distributed in terrestrial and aquatic environments all over the world. Most cyanobacteria can produce the neurotoxin beta-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 (3)H-BMAA on gestational day 14 and postnatal day (PND) 10, respectively, and processed for tape-section autoradiography. The study revealed transplacental transfer of (3)H-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 s.c.) 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.
Karlsson
Oskar
O
Department of Pharmaceutical Biosciences, Uppsala University, 751 24 Uppsala, Sweden.
Lindquist
Nils Gunnar
NG
Brittebo
Eva B
EB
Roman
Erika
E