Evento
An orphan lipid ligand activates resolution pathways in neuron-glia crosstalk
Benzi Juncos, Oriana Nicole
; Alza, Natalia Paola
; Cordero, José; Barrera, Nelson Patricio; Salvador, Gabriela Alejandra
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Tipo del evento:
Reunión
Nombre del evento:
LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; XXV Jornadas Anuales de la Sociedad Argentina de Biología; LV Reunión Anual de la Asociación Argentina de Farmacología Experimental y VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Fecha del evento:
11/2023
Institución Organizadora:
Sociedad Argentina de Investigación Clínica;
Sociedad Argentina de Biología;
Asociación Argentina de Farmacología Experimental;
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio;
Título de la revista:
Medicina (Buenos Aires)
Editorial:
Fundación Revista Medicina
ISSN:
0025-7680
e-ISSN:
1669-9106
Idioma:
Inglés
Clasificación temática:
Resumen
Environmental neurotoxicants, such as Maneb (MB) and other dithiocarbamate pesticides, trigger chronic neuroin- flammation probably due to defective resolution mecha- nisms, leading to neurodegeneration. The inflammation/ resolution balance is governed by a plethora of special- ized pro-resolving lipid mediators (SPM) that act as li- gands of the GPCR receptor FPR2/ALX. SPM are mainly synthetized by lipoxygenases from arachidonic acid (AA) and docosahexaenoic acid (DHA). Thus, our aim was to study the resolution pathway modulated by FPR2/ALX in response to MB challenge in a context of neuro-glial communication. By metabolomics we detected significant changes in 11 metabolites in neurons and 27 metabolites in astrocytes as a response to MB treatment (p<0.05). In both cell types, phosphatidylcholine was reduced with a simultaneous increase in lysophosphatidylcholine. IPA software’s Path Explorer, Connect and MAP functions re- vealed the upregulation of a secretory phospholipase A2, PLA2G2D. GC-MS fatty acid profile showed increased neuronal DHA content and decreased AA and DHA levels in astrocytes (p<0.05). In addition, increased phosphati- dylcholine (DHA/16:0) content in neurons exposed to MB was confirmed by metabolomics. To evaluate resolution events under MB injury in neuron-glia crosstalk, cell-de- rived secretomes and their lipid extracts were used. As- trocyte secretome and its lipid extract were able to revert MB-induced neurotoxicity. This neuroprotective effect was abolished by blocking AA and DHA oxygenation as well as by the FPR2/ALX antagonist Quin-C7. Neurons secreted ERK1/2 -dependent glial proliferation signals, also inhibited by Quin-C7. The role of lipidome obtained from conditioned media in neuro-glia responses to MB injury confirmed the lipid nature of mediators involved in resolution. Our results show that neurons and astrocytes secrete lipid ligands for FPR2/ALX -mediated resolution in re- sponse to MB toxicity.
Palabras clave:
Maneb
,
resolution
,
neuron-glia
,
FPR2/ALX
Archivos asociados
Licencia
Identificadores
Colecciones
Eventos(INIBIBB)
Eventos de INST.DE INVEST.BIOQUIMICAS BAHIA BLANCA (I)
Eventos de INST.DE INVEST.BIOQUIMICAS BAHIA BLANCA (I)
Citación
An orphan lipid ligand activates resolution pathways in neuron-glia crosstalk; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; XXV Jornadas Anuales de la Sociedad Argentina de Biología; LV Reunión Anual de la Asociación Argentina de Farmacología Experimental y VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2023; 64-64
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