title: Early hippocampal cell death, and late learning and memory deficits in rats exposed to the environmental toxin BMAA (β-N-methylamino-L-alanine) during the neonatal period.
abstract: We have reported previously that exposure to the cyanobacterial neurotoxin β-N-methylamino-L-alanine (BMAA) during the neonatal period causes cognitive impairments in adult rats. The aim of this study was to investigate the long-term effects of neonatal BMAA exposure on learning and memory mechanisms and to identify early morphological changes in the neonatal brain. BMAA was injected subcutaneously in rat pups on postnatal days 9-10. BMAA (50 and 200 mg/kg) caused distinct deficits in spatial learning and memory in adult animals but no morphological changes. No impairment of recognition memory was detected, suggesting that neonatal exposure to BMAA preferentially affects neuronal systems that are important for spatial tasks. Histopathological examination revealed early neuronal cell death as determined by TUNEL staining in the hippocampus 24 h after a high dose (600 mg/kg) of BMAA whereas no changes were observed at lower doses (50 and 200 mg/kg). In addition, there was a low degree of neuronal cell death in the retrosplenial and cingulate cortices, areas that are also important for cognitive function. Taken together, these results indicate that BMAA is a developmental neurotoxin inducing long-term changes in cognitive function. The risk posed by BMAA as a potential human neurotoxin merits further consideration, particularly if the proposed biomagnifications in the food chain are confirmed.
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Box 591, SE-751 24 Uppsala, Sweden.
authors.forename: Oskar
authors.initials: O
authors.lastname: Karlsson
authors.forename: Erika
authors.initials: E
authors.lastname: Roman
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Berg
authors.forename: Eva B
authors.initials: EB
authors.lastname: Brittebo
mesh_terms: D000599:Amino Acids, Diamino / Q000633:toxicity*; D000600:Amino Acids, Dicarboxylic / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D016923:Cell Death / Q000502:physiology*; D003071:Cognition / Q000187:drug effects; D000458:Cyanobacteria / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004644:Emotions / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D006624:Hippocampus / Q000473:pathology / Q000502:physiology*; D007859:Learning Disabilities / Q000139:chemically induced* / Q000473:pathology / Q000523:psychology*; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced* / Q000473:pathology / Q000523:psychology*; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000473:pathology*; D009498:Neurotoxins / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects
chemical_list: D000599:Amino Acids, Diamino; D000600:Amino Acids, Dicarboxylic; D009498:Neurotoxins; C064612:alpha-N-carboxy-beta-N-methylaminoalanine