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Neurotoxicology. 2015 May;48:192-205. doi: 10.1016/j.neuro.2015.04.001. Epub 2015 Apr 18.

Analysis of β-N-methylamino-L-alanine (L-BMAA) neurotoxicity in rat cerebellum.

Author information

1
Departamento de Bioquímica y Biología Molecular I, Universidad Complutense de Madrid, 28040 Madrid, Spain. Electronic address: emmamunoz@ucm.es.
2
Departamento de Biología Animal II, Universidad Complutense de Madrid, 28040 Madrid, Spain.
3
Instituto de Química Médica - Centro Superior de Investigaciones Científicas, 28006 Madrid, Spain.
4
Departamento de Biología Celular, Universidad Complutense de Madrid, 28040 Madrid, Spain.
5
Departamento de Bioquímica y Biología Molecular I, Universidad Complutense de Madrid, 28040 Madrid, Spain.

Abstract

Due to its structural similarity to glutamate, L-BMAA could be a trigger for neurodegenerative disorders caused by changes in the intracellular medium, such as increased oxidative stress, mitochondrial dysfunction, impaired synthesis and protein degradation and the imbalance of some enzymes. It is also important to note that according to some published studies, L-BMAA will be incorporated into proteins, causing the alteration of protein homeostasis. Neuronal cells are particularly prone to suffer damage in protein folding and protein accumulation because they have not performed cellular division. In this work, we will analyse the cerebellum impairment triggered by L-BMAA in treated rats. The cerebellum is one of the most important subcortical motor centres and ensures that movements are performed with spatial and temporal precision. Cerebellum damage caused by L-BMAA can contribute to motor impairment. To characterize this neurodegenerative pathology, we first carried out ultrastructure analysis in Purkinje cells showing altered mitochondria, endoplasmic reticulum (ER), and Golgi apparatus (GA). We then performed biochemical assays of GSK3 and TDP-43 in cerebellum, obtaining an increase of both biomarkers with L-BMAA treatment and, finally, performed autophagy studies that revealed a higher level of these processes after treatment. This work provides evidence of cerebellar damage in rats after treatment with L-BMAA. Three months after treatment, affected rats cannot restore the normal functions of the cerebellum regarding motor coordination and postural control.

KEYWORDS:

Autophagy; Cerebellum neurodegeneration; GSK3; L-BMAA; TDP-43; Ultrastructure

PMID:
25898785
DOI:
10.1016/j.neuro.2015.04.001
[Indexed for MEDLINE]

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