Proinflammatory cytokines such as tumor necrosis factor-α and interleukin-1β (IL1β) regulate both excitatory and inhibitory synaptic transmission in the central nervous system. The interaction between IL1β and endocannabinoid system (ECS) is also emerging, based on the evidence that IL1β effects on striatal spontaneous excitatory and inhibitory postsynaptic currents are regulated by transient receptor potential vanilloid 1 (TRPV1) channels, members of the ECS. Furthermore, IL1β has also been shown to control the sensitivity of cannabinoid CB1 receptors controlling GABA transmission (CB1Rs(GABA)) in the striatum. To better detail the synaptic action of IL1β, and to clarify its complex interaction with the ECS, here we investigated the possible interplay between IL1β and CB1Rs controlling glutamate transmission (CB1Rs(glu)), other critical elements of the ECS. Our results show that the sensitivity of CB1Rs(glu) is fully blocked in the presence of IL1β in corticostriatal brain slices, and that the protein kinase C/TRPV1 pathway is involved in this effect. IL1β failed to modulate the sensitivity of glutamate synapses to the stimulation of GABAB receptors. We also provided evidence that IL1β-CB1Rs(GABA) but not IL1β-CB1Rs(glu) interaction is under the control of the brain-derived neurotrophic factor (BDNF)/trkB signaling and of lipid raft composition, because BDNF gene partial deletion, pharmacological blockade of trkB and membrane cholesterol removal with methyl-β-cyclodextrin all blocked IL1β-mediated inhibition of CB1Rs(GABA) but left unaltered the sensitivity of CB1Rs(glu) to this cytokine. Our results provide further evidence that synaptic transmission and the ECS are regulated by IL1β in the striatum.
Keywords: 2-arachidonoylglycerol; 2AG; 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid; 6-cyano-7-nitroquinoxaline-2,3-dione; ACSF; AEA; BDNF; CB1Rs controlling glutamate transmission; CB1Rs((GABA)); CB1Rs((glu)); CNQX; DMSO; ECS; EGTA; HEPES; IL1β; MCD; N-methyl-d-aspartate; NMDA; PKC; PMA; TRPV1; WT; anadamide; artificial cerebrospinal fluid; brain-derived neurotrophic factor; cannabinoid CB1 receptors controlling GABA transmission; cytokines; dimethyl sulfoxide; endocannabinoid system; ethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetra-acetic acid; glutamate; inflammation; interleukin-1β; methyl-β-cyclodextrin; neurodegeneration; phorbol 12-myristate-13-acetate; protein kinase C; sEPSCs; sIPSCs; spontaneous excitatory postsynaptic currents; spontaneous inhibitory postsynaptic currents; synaptic transmission; transient receptor potential vanilloid 1; wild-type.
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