Mechanisms of neuronal degeneration induced by β-N-methylamino-L-alanine (BMAA)

SOTO, T.; DE LOS SANTOS, B.; ROTSTEIN, N; GERMAN, O. L,; POLITI, L.E.

Congreso; XXXIII Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias; 2018

The cyanotoxin BMAA, is a non-proteinogenic amino acid that is released by cyanobacteria present in most water resources around the world. Human chronic intake of this toxin has been linked with the etiology of Amyotrophic Lateral Sclerosis, Parkinson´ and Alzheimer´s diseases. We here investigated the effects of BMAA on pure neuronal and mixed neuro-glial cell cultures, obtained from retinas from newborn rats. Cultures were incubated with BMAA (400 nM) for 5 days. Apoptosis and cell death were evaluated by DAPI and Propidium Iodide (PI) staining, mitochondrial activity by Mitotracker labeling, and cytoskeleton integrity and axonal outgrowth by immunocytochemical methods. In pure neuronal cultures, BMAA induced apoptosis in both amacrine and photoreceptor cells, the two main cell types in these cultures. The percentages of apoptotic amacrine and photoreceptor neurons increased from 22% to 45% and from 33% to 49%, in control and BMAA-treated cultures, respectively. Noteworthy, functional mitochondria decreased significantly in amacrine neurons, and only slightly in photoreceptors. In addition, BMAA disrupted tubulin organization in axons. BMAA induced retraction of lamellipodia and loss of mitochondrial membrane potential in glial cells, without increasing cell death. Noteworthy, glial cells partially prevented BMAA-induced neuronal death. This implies that BMAA induces subcellular changes in both neurons and glial cells, and markedly affects the viability of retinal neurons, suggesting BMAA exposure might contribute to the onset of retina neurodegeneration.