title: Analysis of β-N-methylamino-L-alanine (L-BMAA) neurotoxicity in rat cerebellum.
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.
authors.affiliation: Departamento de Bioquímica y Biología Molecular I, Universidad Complutense de Madrid, 28040 Madrid, Spain. Electronic address: emmamunoz@ucm.es.
authors.forename: Emma
authors.initials: E
authors.lastname: Muñoz-Sáez
authors.affiliation: Departamento de Biología Animal II, Universidad Complutense de Madrid, 28040 Madrid, Spain.
authors.forename: Estefanía
authors.initials: E
authors.lastname: de Munck García
authors.affiliation: Departamento de Biología Animal II, Universidad Complutense de Madrid, 28040 Madrid, Spain.
authors.forename: Rosa Ma
authors.initials: RM
authors.lastname: Arahuetes Portero
authors.affiliation: Instituto de Química Médica - Centro Superior de Investigaciones Científicas, 28006 Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Martínez
authors.affiliation: Departamento de Biología Celular, Universidad Complutense de Madrid, 28040 Madrid, Spain.
authors.forename: Ma Teresa
authors.initials: MT
authors.lastname: Solas Alados
authors.affiliation: Departamento de Bioquímica y Biología Molecular I, Universidad Complutense de Madrid, 28040 Madrid, Spain.
authors.forename: Begoña Gómez
authors.initials: BG
authors.lastname: Miguel
mesh_terms: D000599:Amino Acids, Diamino / Q000633:toxicity*; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology / Q000648:ultrastructure; D000087522:Cyanobacteria Toxins; D004268:DNA-Binding Proteins / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009043:Motor Activity / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D004856:Postural Balance / Q000187:drug effects; D011689:Purkinje Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D000599:Amino Acids, Diamino; D015415:Biomarkers; D000087522:Cyanobacteria Toxins; D004268:DNA-Binding Proteins; C001824:beta-N-methylamino-L-alanine; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3
keywords: Autophagy; Cerebellum neurodegeneration; GSK3; L-BMAA; TDP-43; Ultrastructure