Lack of behavioral and neuropathological effects of dietary beta-methylamino-L-alanine (BMAA) in mice.
Beta-methylamino-L-alanine (BMAA) is an excitotoxin allegedly involved in ALS-parkinsonism-dementia complex (ALS-PDC), a neurological disorder found in Guam and its surrounding islands, in which motor neuron disease symptoms can present alone or can co-occur with parkinsonism and dementia. Although in vitro experiments have shown BMAA's neurotoxic properties, studies using adult animals and systemic administration which better model the case of environmentally-induced human neurodegenerative diseases have not supported the involvement of BMAA in these disorders. In order to better test the hypothesized role of BMAA in neurodegeneration, we fed adult mice BMAA at a dose (28 mg/kg body weight, daily for 30 days) that reproduces the natural levels and tested the animals with a battery of behavioural tests, the latter including the evaluation of motor coordination, motor neuron-mediated reflexes, locomotion, muscular strength and memory. We also assessed whether BMAA exposure triggers cell death in the central nervous system (CNS) of mice by examining neuronal numbers and glial response in the spinal cord and the brain. No motor, cognitive or neuropathological outcome resulted from this feeding paradigm. Our findings support neither the causal role of BMAA in neurodegeneration nor the specific involvement of this amino acid in ALS-PDC.
Cruz-Aguado
Reyniel
R
Department of Ophthalmology, University of British Columbia, Canada. reynielc@yahoo.com
Winkler
Daniella
D
Shaw
Christopher A
CA
D000599:Amino Acids, Diamino / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003071:Cognition / Q000187:drug effects; D000087522:Cyanobacteria Toxins; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009046:Motor Neurons / Q000187:drug effects; D009498:Neurotoxins / Q000494:pharmacology*
D000599:Amino Acids, Diamino; D000087522:Cyanobacteria Toxins; D009498:Neurotoxins; C001824:beta-N-methylamino-L-alanine