The Sphingolipid Receptor S1PR2 Is a Receptor for Nogo-A Repressing Synaptic Plasticity
Figure 6
Blockade of S1PR2 phenocopies the increase in hippocampal and cortical LTP observed upon Nogo-A neutralization.
(A,B) Hippocampal WT (A) and Nogo-A−/− (B) slices were treated with JTE-013 or vehicle (DMSO) (WTDMSO: n = 8; Nogo-A−/−DMSO: n = 10; WTJTE-013: n = 11; Nogo-A−/−JTE-013: n = 9). 60 min after theta-burst stimulation (arrow), a significant difference in LTP could be observed between JTE-013 and DMSO treatment in WT (A) but not Nogo-A−/− (B) slices. (C,D) Input-output strength revealed no differences in JTE-013- versus DMSO-treated slices of WT (C) and Nogo-A−/− (D) mice (WTDMSO: n = 6; Nogo-A−/−DMSO: n = 6; WTJTE-013: n = 7; Nogo-A−/−JTE-013: n = 6). (E,F) PPF revealed no alterations in JTE-013- versus DMSO-treated slices of WT (E) and Nogo-A−/− (F) mice (WTDMSO: n = 7; Nogo-A−/−DMSO: n = 6; WTJTE-013: n = 5; Nogo-A−/−JTE-013: n = 6). (G) LTP was measured upon simultaneous neutralization of S1PR2 using JTE-013 and of Nogo-A using 11c7 (IgG1 + DMSO: n = 7; IgG1 + JTE-013: n = 6; 11c7 + DMSO: n = 8; 11c7 + JTE-013: n = 6). (H) LTP was measured upon simultaneous neutralization of S1PR2 using JTE-013 and of NgR1 using anti-NgR1 (DMSO: n = 7; JTE-013: n = 9; anti-NgR1 + JTE-013: n = 8). (I) Rat motor forelimb area brain slices were treated with JTE-013 (n = 7) or DMSO (n = 8). Peak amplitudes were significantly larger in JTE-013- versus DMSO-treated slices upon repeated inductions of LTP (multiple arrows). (J) Input-output strength revealed no differences in JTE-013- (n = 8) versus DMSO-treated (n = 12) cortical slices. Insets show representative traces. Data shown are means ± SEM (*p<0.05). n indicates the number of mice used.