Abstract |
β-N-methylamino- l-alanine ( L-BMAA) is a neurotoxic amino acid that has been related to various neurodegenerative diseases. The aim of this work was to analyze the biotoxicity produced by L-BMAA in vivo in rats, trying to elucidate its physiopathological mechanisms and to search for analogies between the found effects and pathologies like Amyotrophic Lateral Sclerosis (ALS). Our data demonstrated that the neurotoxic effects in vivo were dosage-dependent. For evaluating the state of the animals, a neurological evaluation scale was developed as well as a set of functional tests. Ultrastructural cell analysis of spinal motoneurons has revealed alterations both in endoplasmic reticulum and mitochondria. Since GSK3β could play a role in some neuropathological processes, we analyzed the alterations occurring in GSK3β levels in L-BMAA treated rats, we have observed an increase in the active form of GSK3β levels in lumbar spinal cord and motor cerebral cortex. On the other hand, (TAR)- DNA-binding protein 43 (TDP-43) increased in L-BMAA treated animals. Our results indicated that N-acetylaspartate (NAA) declined in animals treated with L-BMAA, and the ratio of N-acetylaspartate/ choline (NAA/Cho), N-acetylaspartate/ creatine (NAA/Cr) and N-acetylaspartate/choline+creatine (NAA/Cho+Cr) tended to decrease in lumbar spinal cord and motor cortex. This project offers some encouraging results that could help establishing the progress in the development of an animal model of sporadic ALS and L-BMAA could be a useful tool for this purpose.
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Authors | Estefanía de Munck, Emma Muñoz-Sáez, Begoña G Miguel, M Teresa Solas, Irene Ojeda, Ana Martínez, Carmen Gil, Rosa Mª Arahuetes |
Journal | Environmental toxicology and pharmacology
(Environ Toxicol Pharmacol)
Vol. 36
Issue 2
Pg. 243-255
(Sep 2013)
ISSN: 1872-7077 [Electronic] Netherlands |
PMID | 23688553
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2013 Elsevier B.V. All rights reserved. |
Chemical References |
- Amino Acids, Diamino
- Cyanobacteria Toxins
- DNA-Binding Proteins
- beta-N-methylamino-L-alanine
- Aspartic Acid
- N-acetylaspartate
- Creatinine
- Glycogen Synthase Kinase 3 beta
- Gsk3b protein, rat
- Glycogen Synthase Kinase 3
- Casp3 protein, rat
- Caspase 3
- Choline
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Topics |
- Amino Acids, Diamino
- Amyotrophic Lateral Sclerosis
(chemically induced, metabolism, pathology, physiopathology)
- Animals
- Aspartic Acid
(analogs & derivatives, metabolism)
- Caspase 3
(metabolism)
- Choline
(metabolism)
- Creatinine
(metabolism)
- Cyanobacteria Toxins
- DNA-Binding Proteins
(metabolism)
- Disease Models, Animal
- Endoplasmic Reticulum
(metabolism, pathology)
- Glycogen Synthase Kinase 3
(metabolism)
- Glycogen Synthase Kinase 3 beta
- Magnetic Resonance Spectroscopy
- Male
- Mitochondria
(metabolism, pathology)
- Motor Activity
- Motor Cortex
(metabolism, pathology, physiopathology)
- Nerve Degeneration
- Neurologic Examination
- Phenotype
- Rats
- Rats, Wistar
- Spinal Cord
(metabolism, pathology, physiopathology)
- Time Factors
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