INIBIOLP   05426
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE LA PLATA "PROF. DR. RODOLFO R. BRENNER"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Role of fatty acids on neuronal and dopaminergic differentiation
Autor/es:
ANDRES MARTIN TOSCANI; LISANDRO J. FALOMIR LOCKHART; EZEQUIEL GIMÉNEZ; MARIA ALEJANDRA CARRERO RIVEROS
Lugar:
Bordeaux
Reunión:
Congreso; NeuroFrance 2017; 2017
Institución organizadora:
Société des Neurosciences
Resumen:
Fatty acids (FAs) were classically associated with structural and metabolic roles, as they can be stored as triglycerides, degraded in oxidative phosphorylation or used in phospholipids synthesis, the main component of biological membranes. Recently, it has been shown that lipids exhibit also regulatory functions, similarly as hormones or growth factors. These ?lipokines? bind to specific receptors triggering second messenger´s systems and regulating gene expression. There are two families of FAs receptors: free fatty acid receptors (FFARs) and peroxisome proliferator-activated receptor (PPARs). Central nervous system is enriched in poly-unsaturated fatty acids (PUFAs) such as arachidonic acid (AA), which participates in the regulation of membrane fluidity, axonal growth, development and inflammatory response. Alterations in lipid metabolism are associated with cognitive problems and neurodegenerative diseases, but the molecular mechanism have not yet been described.The aim of the present study is to characterize the effect of FAs in differentiation of SH SY5Y cells, broadly used as model system for in vitro study of neurodegenerative diseases such as Parkinson?s disease. SH SY5Y cells can be differentiated to a more mature, neuron-like phenotype by incubation with 10 µM retinoic acid (RA) for 7 to 10 days. SH-SY5Y differentiation is associated with an increase in Akt expression and phosphorylation levels and, unlike dopaminergic precursors, a decrease in tyrosine hydroxilase (TH). We observed that palmitic acid and AA activates Akt signaling pathway in undifferentiated cells through FFAR1 and FFAR4. Furthermore, addition of AA to differentiation media modulates TH expression and enhances Akt phosphorylation compared to SH-SY5Y cells differentiated only with RA.Our results reveal a new role for FAs in neuronal differentiation. Although they play a key role in neuron physiology by regulating membrane fluidity, PUFAs can also activate signaling cascades downstream membrane receptors. Characterization of the molecular events related to the activation of lipid receptors in the nervous system will provide us a framework to further understand their role in neurophysiology and Parkinson?s disease, where PUFAs are particularly affected by oxidative stress.