Proteoglycans involved in bidirectional communication between mast cells and hippocampal neurons

Journal of Neuroinflammation

María Ángeles Montes¹  Jorge Acosta¹  María Pilar Ramírez-Ponce¹  Eva Alés¹  Guillermo Álvarez de Toledo¹  Juan Antonio Flores¹  Santiago Balseiro-Gómez² 

[1] 0000 0001 2168 1229, grid.9224.d, Dpto. de Fisiología Médica y Biofísica, Facultad de Medicina, Universidad de Sevilla, Av. Sánchez Pizjuán 4, 41009, Sevilla, Spain;0000 0001 2168 1229, grid.9224.d, Dpto. de Fisiología Médica y Biofísica, Facultad de Medicina, Universidad de Sevilla, Av. Sánchez Pizjuán 4, 41009, Sevilla, Spain;0000000419368710, grid.47100.32, Present Address: Department of Neuroscience, Yale School of Medicine, 295 Congress Avenue, 06510, New Haven, CT, USA;

关键词: Ca imaging;    neuro-immune;    hippocampal neurotransmission;    NMDA receptors;    proteoglycans;    exocytosis;   

DOI  :  10.1186/s12974-019-1504-6

来源: publisher

【 摘 要 】

BackgroundMast cells (MCs) in the brain can respond to environmental cues and relay signals to neurons that may directly influence neuronal electrical activity, calcium signaling, and neurotransmission. MCs also express receptors for neurotransmitters and consequently can be activated by them. Here, we developed a coculture model of peritoneal MCs, incubated together with dissociated hippocampal neurons for the study of cellular mechanisms involved in the mast cell-neuron interactions.MethodsCalcium imaging was used to simultaneously record changes in intracellular calcium [Ca2+]i in neurons and MCs. To provide insight into the contribution of MCs on neurotransmitter release in rat hippocampal neurons, we used analysis of FM dye release, evoked by a cocktail of mediators from MCs stimulated by heat.ResultsBidirectional communication is set up between MCs and hippocampal neurons. Neuronal depolarization caused intracellular calcium [Ca2+]i oscillations in MCs that produced a quick response in neurons. Furthermore, activation of MCs with antigen or the secretagogue compound 48/80 also resulted in a neuronal [Ca2+]i response. Moreover, local application onto neurons of the MC mediator cocktail elicited Ca2+ transients and a synaptic release associated with FM dye destaining. Neuronal response was partially blocked by D-APV, a N-methyl-D-aspartate receptor (NMDAR) antagonist, and was inhibited when the cocktail was pre-digested with chondroitinase ABC, which induces enzymatic removal of proteoglycans of chondroitin sulfate (CS).ConclusionsMC-hippocampal neuron interaction affects neuronal [Ca2+]i and exocytosis signaling through a NMDAR-dependent mechanism.

【 授权许可】

CC BY