Fig. 5: astrocytic BDNFpro secretion rescues LTP deficit in p75-flox mice.

a Schematic representation of the experimental design. Step I, deletion of p75^NTR in astrocytes from tamoxifen-treated p75-flox mice precludes proBDNF transfer from neurons to astrocyte following TBS. Step II, LV-BDNFpro^stop transduction replaces BDNFpro in astrocytes. Schematic representation of the experimental paradigms (right); mice were treated with tamoxifen (−5 to 0), injected with lentiviruses the last day of tamoxifen treatment (0 dptm) and finally recorded (14 dptm). LTP evoked in slices from p75-flox mice and control littermates injected with LV-GFP^stop or LV-BDNFpro^stop is shown. ***p < 0.001 (unpaired t-test) (p75-flox/LV-GFP^stop 102.00 ± 1.85%, p75-flox/LV-BDNFpro^stop 177.41 ± 10.74% and control littermates/LV-GFP^stop 165.27 ± 2.24% fEPSP 180 min from TBS; n = 10 slices, 6 mice for p75-flox/LV-GFP^stop; n = 9 slices, 6 mice for p75-flox/LV-BDNFpro^stop; n = 6 slices, 4 mice for control littermates/LV-GFP^stop). b Schematic representation of the experimental design. Step II, and I as in (a). Step III, LV-TeTN^stop transduction in astrocytes prevents from BDNFpro release. Schematic representation of the experimental paradigm as in (a). LTP evoked in slices from p75-flox mice and control littermates injected with LV-GFP^stop or co-injected with LV-GFP^stop/LV-BDNFpro^stop and LV-TeTN^stop/LV-BDNFpro^stop is shown. ***p < 0.001 (unpaired t-test) (p75-flox/LV-BDNFpro^stop/LV-GFP^stop 167.50 ± 8.78%, p75-flox/LV-BDNFpro^stop/LV-TeTN^stop 106.26 ± 2.47% and control littermates/LV-GFP^stop 151.33 ± 7.39% fEPSP 180 min from TBS; n = 8 slices, 6 mice for p75-flox/LV-BDNFpro^stop/LV-GFP^stop; n = 9 slices, 7 mice for p75-flox/LV-TeTN^stop/LV-BDNFpro^stop; n = 7 slices, 4 mice control littermates/LV-GFP^stop). c LTP evoked in slices from p75-flox mice and control littermates. Mice were treated with tamoxifen (−5 to 0) and recorded 14 dptm. Slices were perfused (18–28 min) with vehicle or exogenous BDNFpro. ***p < 0.001 (unpaired t-test) (p75-flox/vehicle 103.54 ± 3.43%, p75-flox/BDNFpro 171.09 ± 10.17% and control littermates/vehicle 162.81 ± 9.87% fEPSP 180 min from TBS; n = 8 slices, 4 mice for p75-flox/vehicle; n = 7 slices, 5 mice for p75-flox/BDNFpro; n = 7 slices, 5 mice for control littermates/vehicle). d LTP evoked as in (c). Slices were perfused (18–28 min) with vehicle or BDNFpro^Val/Met. ***p < 0.001 (unpaired t-test) (p75-flox/vehicle 105.26 ± 1.59%, p75-flox/BDNFpro^Val/Met 148.76 ± 8.69% and control littermates/vehicle 147.55 ± 3.55% fEPSP 180 min from TBS; n = 8 slices, 5 mice for p75-flox/vehicle; n = 6 slices, 4 mice for p75-flox/BDNFpro^Val/Met; n = 7 slices, 5 mice for control littermates/vehicle). Data are presented as mean ± SEM.