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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids, Diamino / toxicity*
  • Animals
  • Autophagy / drug effects
  • Behavior, Animal / drug effects
  • Biomarkers / metabolism
  • Cerebellum / drug effects*
  • Cerebellum / metabolism
  • Cerebellum / physiopathology
  • Cerebellum / ultrastructure
  • DNA-Binding Proteins / metabolism
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / metabolism
  • Endoplasmic Reticulum / ultrastructure
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Golgi Apparatus / drug effects
  • Golgi Apparatus / metabolism
  • Golgi Apparatus / ultrastructure
  • Male
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Mitochondria / ultrastructure
  • Motor Activity / drug effects
  • Neurotoxicity Syndromes / etiology*
  • Neurotoxicity Syndromes / metabolism
  • Neurotoxicity Syndromes / pathology
  • Neurotoxicity Syndromes / physiopathology
  • Neurotoxicity Syndromes / psychology
  • Postural Balance / drug effects
  • Purkinje Cells / drug effects*
  • Purkinje Cells / metabolism
  • Purkinje Cells / ultrastructure
  • Rats, Wistar
  • Signal Transduction / drug effects
  • Time Factors


  • Amino Acids, Diamino
  • Biomarkers
  • DNA-Binding Proteins
  • beta-N-methylamino-L-alanine
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3