Aim: 

Assuming the functional relevance of polyunsaturated fatty acids (PUFA) in nervous tissue and its susceptibility to peroxidative modification in this study we analyzed whether the unsaturation degree of PUFA regulates the outcome of neurodegeneration in several models.

Methods: 

As a chronic neurodegeneration model, we studied a trangenic mouse model (hSODG98A), paradigm of amyotrophyc lateral sclerosis, feeded with diets differing in their PUFA content. As acute neurodegenerative model, we used organotipic lumbar spinal cord cultures and a cell line (NSC34) under oxidative and/or excitotoxic stress. We have measured cellular viability, tissular respiratory capability (by high resolution respirometry) and lipidic profile in those samples.

Results: 

Results demonstrate that diets enriched in PUFA promotes less survival in the mice model, with alterated ubiquitination in the motor region of the spinal cord, a fact that is attributed to fatty acids distinct to DHA. In the organotipic model, we demonstrate a higher neuronal loss for those slices treated with PUFA instead of their precursors, and also altered mitocondrial function. We also demostrate that different PUFA type evoques different proliferative capacity and cytotoxic susceptibility. These parameters are modulated by lipid phase antioxidants (such as olive oil phenolics as hydroxytyrosol or p-HPEA-EDA, as well as a-tocopherol).

Conclusions: 

In summary, the saturation degree of dietary fatty acids and lipid phase-antioxidants alter homeostasis in nervous system when it is exposed to noxious stimuli, such those present in neurodegenerative diseases.