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Issue 1, 2016
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Intravenous injection of L-BMAA induces a rat model with comprehensive characteristics of amyotrophic lateral sclerosis/Parkinson–dementia complex

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Abstract

Non-protein amino acid beta-N-methylamino-L-alanine (L-BMAA) is a neurotoxin that was associated with the high incidence of Amyotrophic Lateral Sclerosis/Parkinson–Dementia Complex (ALS/PDC) in Guam. This neurotoxin has been implicated as a potential environmental factor in amyotrophic lateral sclerosis, Alzheimer's disease and other neurodegenerative diseases, and was found to accumulate in brain tissues of ALS/PDC patients. It is extremely important to establish a reliable animal model that has the comprehensive characteristics of ALS/PDC for studying mechanisms underlying neurodegeneration, and exploring effective therapies. However, very few good animal models that mimic ALS/PDC have been established. In this study, an ideal rat model that mimicked most characteristics of ALS/PDC was established by administering continuous intravenous (i.v.) injections of neurotoxic L-BMAA. Based on the data obtained, it was demonstrated that continuous i.v. injections of L-BMAA induced mitochondrial morphology and structural changes, astrogliosis, motor neuronal death, and other relative functional changes, which led to the overexpression of pro-inflammatory cytokines cyclooxygenase-2 (COX-2), nuclear factor kappa B (NF-κB) and tumor necrosis factor-alpha (TNF-α), and resulted in the upregulation of glycogen synthase kinase-3 (GSK3), downregulation of astrocytic glutamate transporter-1 (GLT-1), accumulation of microtubule-associated protein tau and cytosolic aggregates of TAR DNA-binding protein-43 (TDP-43) in degenerating motor neurons. These results suggest that this model could be used as a useful tool for the mechanistic and therapeutic study of ALS/PDC.

Graphical abstract: Intravenous injection of l-BMAA induces a rat model with comprehensive characteristics of amyotrophic lateral sclerosis/Parkinson–dementia complex

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Publication details

The article was received on 04 Aug 2015, accepted on 02 Nov 2015 and first published on 10 Nov 2015


Article type: Paper
DOI: 10.1039/C5TX00272A
Citation: Toxicol. Res., 2016,5, 79-96
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    Intravenous injection of L-BMAA induces a rat model with comprehensive characteristics of amyotrophic lateral sclerosis/Parkinson–dementia complex

    K. Tian, H. Jiang, B. Wang, F. Zhang and S. Han, Toxicol. Res., 2016, 5, 79
    DOI: 10.1039/C5TX00272A

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