A key role for sphingosine-1-phosphate in the crosstalk between retina glial and neuronal cells.

ABRAHAN C.E.; POLITI L.E.; ROTSTEIN N.P.

Huerta Grande, Cordoba

Congreso; 1ª Reunión Conjunta SAN-Taller Argentino de Neurociencias; 2009

Sociedad Argentina de Investigacion en Neurociencias- Taller Argentino de Neurociencias

<!-- /* Font Definitions */ @font-face {font-family:"Arial Unicode MS"; panose-1:2 11 6 4 2 2 2 2 2 4; mso-font-charset:128; mso-generic-font-family:swiss; mso-font-pitch:variable; mso-font-signature:-1 -369098753 63 0 4129279 0;} @font-face {font-family:"@Arial Unicode MS"; panose-1:2 11 6 4 2 2 2 2 2 4; mso-font-charset:128; mso-generic-font-family:swiss; mso-font-pitch:variable; mso-font-signature:-1 -369098753 63 0 4129279 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0in; margin-bottom:.0001pt; mso-pagination:none; mso-hyphenate:none; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Arial Unicode MS"; mso-font-kerning:.5pt; mso-fareast-language:#00FF;} @page Section1 {size:595.25pt 841.85pt; margin:56.7pt 56.7pt 56.7pt 56.7pt; mso-header-margin:.5in; mso-footer-margin:.5in; mso-paper-source:0;} div.Section1 {page:Section1; mso-footnote-position:beneath-text;} --> A key role for sphingosine-1-phosphate in the crosstalk between retina glial and neuronal cells. Abrahan C, Politi L, Rotstein NP. Instituto de Investigaciones Bioquímicas, UNS-CONICET. Bahía Blanca, Argentina.   We have previously shown that Müller glial cells in coculture preserve the proliferative potential of neuronal progenitors and protect neurons from oxidative stress, while this stress enhances their proliferation. We have also identified the sphingolipid sphingosine-1-phosphate (S1P) as a crucial mediator in key cellular processes in photoreceptors, such as neuroblast proliferation, survival and differentiation. We have now investigated the roles played by S1P in neuroglial crosstalk. Inhibiting S1P synthesis before treating neuroglial cocultures with the oxidant paraquat blocked glial protection from oxidative stress-induced apoptosis in neurons; adding an antagonist to S1P3 receptor, a protein membrane receptor for S1P, similarly inhibited this protection. Incubation of neuroglial cocultures with exogenous S1P increased Br-deoxiuridine (BrdU) uptake in neuroblasts. An increased [3H]thymidine and BrdU uptake after S1P supplementation of glial cultures suggests S1P promoted glial cell proliferation as well. S1P also regulated neuronal differentiation and organization on neuroglial cocultures. S1P induced neuronal migration, promoted their initial aggregation and rearrangement in a radial disposition and then led to the formation of a larger number of aggregates respect to the controls. Thick bundles of neuronal axons connected these aggregates, forming an extensive network absent in controls. Concurrently, S1P increased the expression of N-CAM, a cell adhesion molecule. Our results suggest that S1P is one of the factors released by glial cells to prevent neuronal apoptosis, it promotes glial and neuronal proliferation and might also contribute to the establishment of neuronal networks.