Acute 𝛽-N-Methylamino-L-alanine Toxicity in a Mouse Model

Authors

Maitham Ahmed Al-Sammak, University of Nebraska - LincolnFollow
Douglas G. Rogers, University of Nebraska - LincolnFollow
Kyle D. Hoagland, University of Nebraska-LincolnFollow

Document Type

Article

Date of this Version

2016

Citation

Journal of Toxicology Volume 2015, Article ID 739746, 9 pages

Comments

Copyright © 2015 Maitham Ahmed Al-Sammak et al.

Open access

http://dx.doi.org/10.1155/2015/739746

Abstract

The cyanobacterial neurotoxin 𝛽-N-methylamino-L-alanine (BMAA) is considered to be an “excitotoxin,” and its suggested mechanism of action is killing neurons. Long-termexposure to L-BMAAis believed to lead to neurodegenerative diseases including Parkinson’s and Alzheimer’s diseases and amyotrophic lateral sclerosis (Lou Gehrig’s disease). Objectives of this study were to determine the presumptive median lethal dose (LD50), the Lowest-Observed-Adverse-Effect Level (LOAEL), and histopathologic lesions caused by the naturally occurring BMAA isomer, L-BMAA, in mice. Seventy NIH Swiss Outbred mice (35 male and 35 female) were used. Treatment group mice were injected intraperitoneally with 0.03, 0.3, 1, 2, and 3mg/g body weight L-BMAA, respectively, and control mice were sham-injected.The presumptive LD₅₀ of L-BMAA was 3mg/g BWand the LOAEL was 2mg/g BW.There were no histopathologic lesions in brain, liver, heart, kidney, lung, or spleen in any of the mice during the 14-day study. L-BMAA was detected in brains and livers in all of treated mice but not in control mice.Males injected with 0.03mg/g BW, 0.3mg/g BW, and 3.0mg/g BW L-BMAA showed consistently higher concentrations (P < 0.01) in brain and liver samples as compared to females in those respective groups.