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

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

Congreso; SAN 2018; 2018

SAN

The non-proteic aminoacid BMAA is released by many cyanobacteria present in most dams and water resources around the world. Human chronic intake of this toxin has been linked with the development of Amyotrophic Lateral Sclerosis, Parkinson and Alzheimer Disease. We here investigated its effects on pure neuronal and mixed neuro-glial cells cultures, obtained from newborn rat retinas. 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 labelling and cytoskeleton integrity and axonal outgrowth by immunocytochemical methods. In pure neuronal cultures BMAA increased the percentage of apoptotic amacrine and photoreceptor neurons, from 22% to 45% and from 33% to 49%, in controls and BMAA-treated cultures, respectively. Noteworthy, functional mitochondria decreased significantly in amacrine neurons, and only slightly in photoreceptors. In addition, BMAA disrupted the organized assembly of tubulin in axons. In neuro-glial cultures, BMAA induced lamellipodia retraction and loss of mitochondrial membrane potential in glial cells, without increasing glial cell death. Noteworthy, glial cells partially prevented BMAA-induced neuronal death. This suggest that BMAA induces subcellular changes in both neurons and glial cells, and markedly affects the viability of retinal neurons, confirming its threat to human health as a potential inducer of neurodegenerative damages.