Figure 1
From: Uncoupling DAPK1 from NMDA receptor GluN2B subunit exerts rapid antidepressant-like effects
Chronic unpredictable stress increased extracellular glutamate levels and activated extrasynaptic GluN2B-containing NMDARs in the mPFC. (a) Timeline of CUS exposure, behavioral testing and microdialysis (n=4–5 per group). (b) Photograph of microdialysis site in the mPFC. (c) Extracellular glutamate in CUS-exposed rats was significantly higher than that in control rats. The levels of glutamate were measured every 30 min for 3 h after probe equilibration in the mPFC. (d) Timeline of CUS exposure and sample collection (n=8 per group). (e, f) Representative western blots and quantification of fold changes in GLT-1 and GFAP expression in the mPFC relative to control. (g) Representative image of GFAP-labeled astrocytes in the mPFC, counterstained with DAPI. Scale bar=50 μm. (h) Results are expressed as mean±s.e.m. of GFAP-positive cells per mm2. n=4 per group. (i) Representative EPSC traces. (j) Plot of the normalized and averaged amplitudes of NMDAR EPSCs that were evoked at 40 Hz in the mPFC at a holding potential of +50 mV in the presence and absence of ifenprodil (n=6 neurons per group). (k) Average decay time constant of NMDAR EPSCs that were evoked by 12 pulses at 40 Hz stimulation in the presence and absence of ifenprodil. The data are expressed as mean±s.e.m., *P<0.05, **P<0.01, compared with control group; #P<0.05, compared with CUS+vehicle group. CUS, chronic unpredictable stress; DAPI, 4′,6-diamidino-2-phenylindole; EPSC, excitatory postsynaptic current; GFAP, glial fibrillary acidic protein; GLT-1, glutamate transporter 1; mPFC, medial prefrontal cortex; NMDAR, N-methyl-D-aspartate receptor.
