Figure 4
From: Uncoupling DAPK1 from NMDA receptor GluN2B subunit exerts rapid antidepressant-like effects
Knockdown of DAPK1 prevented CUS-induced depressive-like behavior and normalized GluN2B signaling in the mPFC. (a) Representative photographs of the injection sites and coronal brain sections in the mPFC. The figure shows representative micrographs of adeno-associated virus (AAV)-mediated enhanced green fluorescent protein (eGFP; green) after mPFC microinjection. Scale bars=100 μm (low-magnification images) and 50 μm (high-magnification images). (b) DAPK1 expression in the mPFC in rats that were microinfused with AAV-Scramble or AAV-shDAPK1, quantified by western blot. **P<0.01, compared with the AAV-Scramble group. n=6 per group. (c) Timeline of AAV microinjection, CUS exposure and behavioral testing (n=8–18 per group). (d–f) Intra-mPFC microinjection of AAV-shDAPK1 prevented the decrease in sucrose preference (d) and did not affect total fluid consumption (e) in the SPT, and prevented the increase in immobility time in the FST (f) induced by CUS. (g) Representative western blots and quantification of fold changes in GluN1, DAPK1, GluN2B, p-GluN2B, CREB, p-CREB and BDNF in the mPFC after AAV-Scramble or AAV-shDAPK1 microinjection (n=8 per group). The data are expressed as mean±s.e.m. *P<0.05, **P<0.01, compared with control+AAV-Scramble group; ##P<0.01, compared with CUS+AAV-Scramble group. BDNF, brain-derived neurotrophic factor; CREB, cyclic AMP response element-binding protein; CUS, chronic unpredictable stress; DAPK1, death-associated protein kinase 1; FST, forced swim test; mPFC, medial prefrontal cortex; SPT, sucrose preference test.
